Dept of Anaesthesiology

DEPT OF ANAESTHESIOLOGY

Researcher : Cheung CW

Project Title:	The analgesic and diuretic effects of dexmedetomidine in dental surgery under general anaesthesia
Investigator(s):	Cheung CW, Ng JKF
Department:	Anaesthesiology
Source(s) of Funding:	Small Project Funding
Start Date:	08/2008

Abstract:

Hypothesis We hypothesise that the injection of dexmedetomidine into site of local tissue injury will provide analgesia via the action on the peripheral alpha 2 receptors. The magnitude of this effect will be compared with IV dexmedetomidine as well as a placebo injection. Further, we aim to demonstrate that dexmedetomidine exerts a diuretic effect in patients undergoing general anaethesia

Project Title:	Multimodal analgesic using morphine and COX-2 with or without dexmedetomidine for laparoscopic colorectal surgery
Investigator(s):	Cheung CW, Ng JKF
Department:	Anaesthesiology
Source(s) of Funding:	Small Project Funding
Start Date:	08/2009

Abstract:

This study aims to compare and evaluate: ◊ The efficacy of using PCA morphine plus intraoperative morphine with dexmedetomidine versus PCA morphine plus intraoperative morphine only for postoperative pain relief after laparoscopic colorectal surgery ◊ The effect of dexmedetomidine on the time of anaesthesia and recovery ◊ The cardiostability of dexmedetomidine ◊ The effect on postoperative bowel function, tolerability of diet, ambulatory function and time of discharge of the two different multimodal analgesic management ◊ The adverse effects of the two regimens Hence, determine the efficacy and adverse effects of using two different multimodal an-algesic modalities for pain relief after laparoscopic colorectal surgery.

List of Research Outputs

Cheng T.H., Leung Y.M., Cheung C.W., Chen C.H., Chen Y.L. and Wong K.L., Propofol depresses angiotensin II-induced cell proliferation in rat cardiac fibroblasts, Anesthesiology. 2010, 112: 108-118.

Cheung C.W., Chairman, Free Paper Session, Annual Scientific Meeting in Anaesthesiology, Hong Kong.. 2009.

Cheung C.W., Chairman, Pain Management II, The 13th Asian Australasian Congress of Anaesthesiologiss, Fukuoka International Conference Center, Fukuoka, Japan. 2010.

Cheung C.W., Peer Reviewer, International Journal of Oral and Maxillofacial Surgery . 2010.

Cheung C.W., Speaker, Alpha-agonist in postoperative pain management, 10th ASIAN and OCEANIA Congress of Regional Anesthesia and Pain Medidcine, Jianan, China.. 2009.

Cheung C.W., Speaker, Cancer Pain Managemet in Asia (Hong Kong), Expert Meeting for Cancer Pain Management, New Update of Cancer Pain Management Symposium, Janssen Cilag. The Grand Hyatt Seoul, Seoul, South Korea.. 2009.

Cheung C.W., Speaker, Chronic Pain Management at Explore the World of Medicine: Public Lecture Series2009, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Central Library. 2009.

Cheung C.W., Speaker, Ketamine on Complex Regional Pain Sydnrome (CRPS) type I in rats, at Anesthesiologic Sympoisum 2009, Shanghai Society in Anesthesiology. 2009.

Cheung C.W., Speaker, New Era in Neuropathic Pain Management., The Annual Scientific Meeting of Macau Health Bureau Doctors' Association 2010, Macau. 2010.

Cheung C.W., Speaker, New Trends in Pain Pharmacotherapy at Symposium ofNew Insights in Pain Management, Annual Scientific Meeting 2010, Hong Kong Pain Society, Hong Kong. 2010.

Cheung C.W., Speaker, Sedation Safety, Associacao Chinesa Dos Profissionais de Medicina de Macau. 2010.

Liman S., Cheung C.W. and Ng J.K.F., Serum pro-inflammatory indiced in chronic post-ischemia pain (CPIP) rat model of complex regional pain syndrome (CRPS) type I, The American Society for Clinical Investigation (ASCI)/The Association of Americal Physicians (AAP) 2010 Joing Meeting. 2010.

Researcher : Chou CW

List of Research Outputs

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., DIFFERENTIAL EXPRESSION OF P65 AND P50 IN THE RAT'S HYPOTHALAMUS INDUCED BY CHRONIC CONSTRICTION NERVE INJURY , Third International Congress on Neuropathic pain (Athens). 2010.

Chou C.W., Wong G.T.C., Wang S., Lim G., Irwin M.G. and Mao J., Differential expression of p65 NF-κB in the rat’s brain regions induced by chronic constriction nerve injury , NeuroScience 2009 Chicago; Society for Neuroscience. 2009.

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., Spatiotemporal Pattern of Concurrent Spinal and Supraspinal NF-kappaB Expression After Peripheral Nerve Injury, Journal of Pain. 2010, 1-9.

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., Spatiotemporal pattern of concurrent spinal ad supraspinal NF-kappab expression after peripheral nerve injury, J Pain. 2010.

Researcher : Chou CW

List of Research Outputs

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., Spatiotemporal pattern of concurrent spinal ad supraspinal NF-kappab expression after peripheral nerve injury, J Pain. 2010.

Researcher : Huang Z

List of Research Outputs

Wong G.T.C., Huang Z., Ji S. and Irwin M.G., Remifentanil Reduces the Release of Biochemical Markers of Myocardial Damage After Coronary Artery Bypass Surgery: A Randomized Trial , Journal of Cardiothoracic Vascular Anesthesia. 2010, 790-796.

Wong G.T.C., Huang Z. and Irwin M.G., Remifntanil reduces the release of biochemical arkes of myocardial damage after coronary artery bypass surgery. A randomized trail., J Cardiothorac Vasc Anesth. 2010.

Xia Z., Huang Z., Ji S.Y., Xia Z.Y. and Irwin M.G., Isoflurane and Propofol Synergy in Reducing Myocardial Ischemia-Reperfusion Injury in Patients, Anesthesiology. 2009, 111: A285.

Researcher : Hui TWC

List of Research Outputs

Chung P.H.Y., Wong K.K.Y., Tam P.K.H., Chan K.L., Ng K.K.C., Chan S.C., Hui T.W.C., Yong B.H., Fan S.T. and Lo C.M., Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series). 2009, 14: 181-185.

Researcher : Irwin MG

Project Title:	A comparative study of hydroxyethyl starch (130/0.4) and gelatin on the immune response in paediatric scoliosis surgery
Investigator(s):	Irwin MG, Wylie SJ
Department:	Anaesthesiology
Source(s) of Funding:	Small Project Funding
Start Date:	01/2009

Abstract:

i. To determine whether colloid administration has an effect on the inflammatory response to paediatric scoliosis surgery. HES 130/0.4 (Voluven®) will be compared with succinylated gelatine (Gelofusine®). ii. To determine whether there is an association between the type of colloid administered (Voluven® or Gelofusine®) and post-operative pain iii. To assess gastrointestinal recovery profile by looking at: a. time to first solid food intake b. incidence of nausea and vomiting iv. Effects of HES 130/0.4 versus gelatin on renal function.

Project Title:	NADPH Oxidase Over Expression in the Myocardium of Diabetic Rats Compromises Opioid Agonist Induced Cardioprotection
Investigator(s):	Irwin MG, Vanhoutte PMGR, Xia Z
Department:	Anaesthesiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	10/2009

Abstract:

1) To determine the role of NADPH oxidase activation in delta and/or kappa opioid agonist mediated acute cardioprotection in normal and hearts of diabetic rats and its relationship with PKC activation; 2) To determine whether delta and kappa opioid agonists can confer synergistic cardioprotection in the hearts of normal and of diabetic rats: a comparison with the multi-opioid receptor agonist remifentanil (a short acting opioid with a very favourable clinical pharmacokinetic profile); 3) To investigate whether or not chronic treatment with N-acetyl cysteine (NAC) or the PKC-beta2 inhibitor LY 333531 can restore heart sensitivity to opioid preconditioning in diabetic rats and, if so, to determine the role of NADPH oxidase activation in this process.

Project Title:	A Comparison of Two doses of Intranasal Dexmedetomidine for Premedication in Children – a double-blind randomized controlled trial
Investigator(s):	Irwin MG, Yuen VMY, Wong GLS, Yao TJ, Hui TWC
Department:	Anaesthesiology
Source(s) of Funding:	Small Project Funding
Start Date:	12/2009

Abstract:

Previous clinical trials have shown that intranasal dexmedetomidine (InDex) at a dose of 1mcg/kg produced satisfactory sedation in more than 60% of children at parental separation and at the time of intravenous cannulation (1,2). Moreover more than 50% of the children remained sedated when they underwent anaesthetic induction (1,2). Dexmedetomidine is an effective and safe sedative for children in the critical care setting (3-6), various diagnostic procedures (7-13) and preoperatively (1,2,14,15). Intravenous 3mcg/kg doses of dexmedetomidine produces reliable sedation in 97% of children undergoing Magnetic Resonance Imaging with acceptable cardiovascular effects (11). There are also case reports on the safe use of these larger doses of InDex (16,17) or oral dexmedetomidine in children (18). The aim of this clinical trial is to determine whether InDex 2 mcg/kg will be more efficacious than1 mcg/kg as premedication in children aged 1 to 12 years. We hypothesize that 2mcg/kg InDex will produce satisfactory sedation in more children than with the 1 mcg/kg dose at the time of anaesthetic induction. 1. Yuen VM, Hui TW, Irwin MG, Yuen MK. A Comparison of Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Anesthesia: A Double-Blinded Randomized Controlled Trial. Anesthesia and analgesia 2008;106:1715-21. 2. Yuen VM, Hui TW, Yuen MK, Irwin MG, Yao TJ. Evaluation of the sedative effect of intranasal dexmedetomidine in children (Abstract). Pediatric Sedation Outside of the Operating Room, September 13-14, 2008 Harvard Medical School, Department of Continuing Education 2008 3. Hammer GB, Philip BM, Schroeder AR, Rosen FS, Koltai PJ. Prolonged infusion of dexmedetomidine for sedation following tracheal resection. Paediatric anaesthesia 2005;15:616-20. 4. Diaz SM, Rodarte A, Foley J, Capparelli EV. Pharmacokinetics of dexmedetomidine in postsurgical pediatric intensive care unit patients: preliminary study. Pediatr Crit Care Med 2007;8:419-24. 5. Chrysostomou C, Di Filippo S, Manrique AM, Schmitt CG, Orr RA, Casta A, Suchoza E, Janosky J, Davis PJ, Munoz R. Use of dexmedetomidine in children after cardiac and thoracic surgery. Pediatr Crit Care Med 2006;7:126-31. 6. Buck ML, Willson DF. Use of dexmedetomidine in the pediatric intensive care unit. Pharmacotherapy 2008;28:51-7. 7. Berkenbosch JW, Wankum PC, Tobias JD. Prospective evaluation of dexmedetomidine for noninvasive procedural sedation in children. Pediatr Crit Care Med 2005;6:435-9; quiz 40. 8. Koroglu A, Teksan H, Sagir O, Yucel A, Toprak HI, Ersoy OM. A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging. Anesthesia and analgesia 2006;103:63-7, table of contents. 9. Mason KP, Zgleszewski SE, Dearden JL, Dumont RS, Pirich MA, Stark CD, D'Angelo P, Macpherson S, Fontaine PJ, Connor L, Zurakowski D. Dexmedetomidine for pediatric sedation for computed tomography imaging studies. Anesthesia and analgesia 2006;103:57-62, table of contents. 10. Mason KP, Zgleszewski SE, Prescilla R, Fontaine PJ, Zurakowski D. Hemodynamic effects of dexmedetomidine sedation for CT imaging studies. Paediatric anaesthesia 2008;18:393-402. 11. Mason KP, Zurakowski D, Zgleszewski SE, Robson CD, Carrier M, Hickey PR, Dinardo JA. High dose dexmedetomidine as the sole sedative for pediatric MRI. Paediatric anaesthesia 2008;18:403-11. 12. Munro HM, Tirotta CF, Felix DE, Lagueruela RG, Madril DR, Zahn EM, Nykanen DG. Initial experience with dexmedetomidine for diagnostic and interventional cardiac catheterization in children. Paediatric anaesthesia 2007;17:109-12. 13. Tosun Z, Akin A, Guler G, Esmaoglu A, Boyaci A. Dexmedetomidine-ketamine and propofol-ketamine combinations for anesthesia in spontaneously breathing pediatric patients undergoing cardiac catheterization. Journal of cardiothoracic and vascular anesthesia 2006;20:515-9. 14. Schmidt AP, Valinetti EA, Bandeira D, Bertacchi MF, Simoes CM, Auler JO, Jr. Effects of preanesthetic administration of midazolam, clonidine, or dexmedetomidine on postoperative pain and anxiety in children. Paediatric anaesthesia 2007;17:667-74. 15. Zub D, Berkenbosch JW, Tobias JD. Preliminary experience with oral dexmedetomidine for procedural and anesthetic premedication. Paediatric anaesthesia 2005;15:932-8. 16. Cohen MS, Aboulleish AE, Mueller M, Elkon D. Intranasal dexmedetomidine for sedation during CT scanning (Abstract). Annual Meeting Abstracts A998, American Society of Anesthesiologists 2008. 17. Walsh DL, Steiner JW, Hoang SQ, Pop RB, Szmuk P. Use of intranasal dexmedetomidine for peroperative sedation in fifteen pediatric patients (Abstract). Annual Meeting Abstracts A1378, American Society of Anesthesiologists 2008. 18. Sakurai Y, Tamura M, Miyao H. The application of oral dexmedetomidine for the premedication of children (Abstract). Annual Meeting Abstracts A1379, American Society of Anesthesiologists 2008.

List of Research Outputs

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., DIFFERENTIAL EXPRESSION OF P65 AND P50 IN THE RAT'S HYPOTHALAMUS INDUCED BY CHRONIC CONSTRICTION NERVE INJURY , Third International Congress on Neuropathic pain (Athens). 2010.

Chou C.W., Wong G.T.C., Wang S., Lim G., Irwin M.G. and Mao J., Differential expression of p65 NF-κB in the rat’s brain regions induced by chronic constriction nerve injury , NeuroScience 2009 Chicago; Society for Neuroscience. 2009.

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., Spatiotemporal Pattern of Concurrent Spinal and Supraspinal NF-kappaB Expression After Peripheral Nerve Injury, Journal of Pain. 2010, 1-9.

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., Spatiotemporal pattern of concurrent spinal ad supraspinal NF-kappab expression after peripheral nerve injury, J Pain. 2010.

Irwin M.G., Acute Pain Management, Pfizer Advisor Board Meeting, Laos. 2009.

Irwin M.G., Editor, CPD Anaesthesia (UK). 2010.

Irwin M.G., Fit for surgery, HKU Head and Neck Surgery Course. 2010.

Irwin M.G., Gabapentinods; New drug debate, ANZCA ASM, Christchurch. 2010.

Irwin M.G., Neurobiology and merchanisms of pain, Multidisciplinary Pain Medicine. 2009.

Irwin M.G., Neurokinin antagonists; sedation workshop; fluid therapy in intensive care, 16th Asian Congress of Anaesthesiologists & 7th National Conference on Intensive Care. Malaysia July . 2009.

Irwin M.G., Occupational Exposure to Anaesthetic Agents, Phillippine Society of Anesthesiologists, Annual Scientific Meeting. 2009.

Irwin M.G., Trinh T.P. and Yao C.L., Occupational exposure to anaesthetic gases - a role for TIVA, Expert Opinion in Drug Safety. 2009, 8(4): 473-483.

Irwin M.G., Pain Management, Int Orthopaedic Tumour Meeting, Cebu. 2010.

Irwin M.G., Panel Member, Faculty 1000 Medicine (cardiovascular drugs in anaesthesia). 2010.

Irwin M.G., Peer Reviewer, Anaesthesia. 2010.

Irwin M.G., Peer Reviewer, Anaesthesia and Intensive Care. 2010.

Irwin M.G., Peer Reviewer, Anesthesia & Analgesia. 2010.

Irwin M.G., Peer Reviewer, Anesthesiology. 2010.

Irwin M.G., Peer Reviewer, Asean Journal of Anaesthesiology. 2010.

Irwin M.G., Peer Reviewer, Asian Journal of Maxillofacial Surgery. 2010.

Irwin M.G., Peer Reviewer, Canadian Journal of Anaesthesia. 2010.

Irwin M.G., Peer Reviewer, Canadian Journal of Physiology & Pharmacology. 2010.

Irwin M.G., Peer Reviewer, Expert Opinion on Pharmacotherapy. 2010.

Irwin M.G., Peer Reviewer, Hong Kong Medical Journal. 2010.

Irwin M.G., Peer Reviewer, Jounral of Paediatrics. 2010.

Irwin M.G., Peer Reviewer, Jounral of Pharmaceutical & Biomedical Analysis. 2010.

Irwin M.G., Peer Reviewer, Journal of Clinical Anaesthesia. 2010.

Irwin M.G., Peer Reviewer, Medical Science Montior. 2010.

Irwin M.G., Peer Reviewer, Obstetrics and Gynaecology. 2010.

Irwin M.G., Peer Reviewer, Surgical Practice. 2010.

Irwin M.G., Perioperative Sedation; Goal Directed Fluid Therapy; Neurokinin Antagonists, 16th Asean Congress of Anaesthesiologists. 2009.

Irwin M.G., Perioperative cardioprotection, Fluid Management, ISOA Jakarta. 2010.

Irwin M.G., Practical TIVA, Pilippine Society of Anesthesiologiss. 2009.

Irwin M.G., Referee, Health Services Research Committee/Health Care & Promotion Fund Committee. 2010.

Irwin M.G., Referee, Hong Kong Research Grants Council. 2010.

Irwin M.G., Safe sedation for non anaesthesiologists, HKAM CEM program. 2010.

Irwin M.G., Sesis; Depth of Anaesthesia; Safe use of TCI, FRACTA. 2010.

Irwin M.G., The Perfect Investigator, Clinical Trial Magnifier. 2009.

Irwin M.G., The magc of opioids: cardioprotection and more, European Society o Anaesthesiology, Helsinki. 2010.

Irwin M.G., The perfect investigator, 1st Clinical Trail magnifier, Hong Kong. 2009.

Irwin M.G., arious TIVA topics, Hospial visit program. Seoul. 2010.

Jiang L., Wong G.T.C., Zhu B. and Irwin M.G., Intrathecal Morphine Postconditioning reduces cardiac ischemia reperfusion injury via central opioid receptor activation, 18th Annual Meeting of The International Society of Anaesthetic Pharmacology, New Orleans. 2009.

Liu H., Liu K.X., Cheng M.H., Liu Y., Lei S., Irwin M.G. and Xia Z., Bosentan Affects 15-F2t-Isoprostane Adverse Effects on Postischemic Rat Hearts, Journal of Surgical Research. 2009, 155: in press.

Liu H., Lei S., Luo T., Xia Z.Y., Liu Y., Leung G.P.H., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., Nitroglycerin Reduces TNF- Toxicity To Endothelial Cells but Compromises the Protective Effects of Propofol, FASEB Journal. 2010, 24: 959.9.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., PKC β inhibitor ruboxistaurin prevents the increase of 15-F2tisoprostane in the myocardium and plasma in Type 1 diabetic rats, FASEB Journal . 2010, 24: 572.1.

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Interaction between spinal opioid and adenosine receptors in the remote cardiac preconditioning effect of intrathecal morphine, J of Cardiothorac Vasc Anesth. 2010, in press.

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Intrathecal Morphine Remotely Preconditions The Heart Via Multiple Neural Pathways In The Rat, 2010 Annual Scientific Meeting of the Australian and New Zealand College of Anaesthetists. 2010.

Tam M.K., Irwin M.G., Tse M.L., Lui Y.W., Law K.I. and Ng P.W., Prolonge myoclonus after a single bolus dose of propofol, Anaesthesia. 2009, 64(11): 1254-1257.

Wong G.T.C., Jiang L. and Irwin M.G., Activation of Central Opioid Receptors Induces Cardioprotection Against Ischemia-Reperfusion Injury , Anesthesia and Analgesia. 2009, 111(1): 24-28.

Wong G.T.C. and Irwin M.G., Pretreatment Time with Norbinaltorphimine , Anesthesia and Analgesia . 2010, 110: 1244.

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil Post-conditioning Attenuates Cardiac Ischemia–reperfusion Injury Via Κ Or Δ Opioid Receptor Activation, Acta Anaesthesiologica Scandinavica. 2010, 54: 510-518.

Wong G.T.C., Huang Z., Ji S. and Irwin M.G., Remifentanil Reduces the Release of Biochemical Markers of Myocardial Damage After Coronary Artery Bypass Surgery: A Randomized Trial , Journal of Cardiothoracic Vascular Anesthesia. 2010, 790-796.

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil postconditioning attenuates cardiac ischemia-reperfusion injury via kappaor delta opioid receptor activation, Acta naesthesiologia Scandinavica. 2010, 54(4): 510-518.

Wong G.T.C., Huang Z. and Irwin M.G., Remifntanil reduces the release of biochemical arkes of myocardial damage after coronary artery bypass surgery. A randomized trail., J Cardiothorac Vasc Anesth. 2010.

Xia Z., Liu H., Xia Z.Y., Liu Y., Lei S., Mao X. and Irwin M.G., Endothelin-1 blockade with bosentan attenuates15-F2t-Isoprostane adverse effects on postischemic rat hearts, FASEB Journal . 2010, 24: 573.3.

Xia Z. and Irwin M.G., Esmolol May Abolish Volatile Anesthetic-Induced Postconditioning By Scavenging Reactive Oxygen Species, Anesthesiology. 2009, 111(4): 1-1.

Xia Z. and Irwin M.G., Isoflurane & Propofol Synergistically Reduce Post Ischemic TNF alpha Release with Cardioplumonary Bypass. Best in Show Abstract Award (Honorable Mention), International Society for Anesthetic Pharmacology, USA. 2009.

Xia Z., Huang Z., Ji S.Y., Xia Z.Y. and Irwin M.G., Isoflurane and Propofol Synergy in Reducing Myocardial Ischemia-Reperfusion Injury in Patients, Anesthesiology. 2009, 111: A285.

Xia Z., Luo T., Liu H.M., Wang F., Xia Z.Y. and Irwin M.G., L-Arginine enhances nitrative stress and exacerbates TNF-Alpha toxicity to human endothelial cells in culture: prevention by propofol, Journal of Cardiovascular Pharmacology. 2010, 54(7): 358-367.

Xia Z., Luo T., Liu H., Wang F., Xia Z.Y., Irwin M.G. and Vanhoutte P.M.G.R., L-arginine enhances nitrative stress and exacerbates tumor necrosis factor-alpha toxicity to human endothelial cells in culture: prevention by propofol, Journal of Cardiovascular Pharmacology. 2010, 55(4): 358-67.

Yang L.Q., Song J.C., Irwin M.G., Song J.G., Sun Y.M. and Yu W.F., A clinical prospecrive comparison of anesthetics sensitivity and hemodynamic effect among patients with or without obstructive jaundice, Acta Aaesthesiol Scand. 2010, 54(7): 871-877.

Zhang Y., Irwin M.G., Li R., Chen Z.W. and Wong T.M., Effects of remifentanil on intracellular Ca2+ and its ransients induced by electrical stimulation and caffine inrat ventricuar myocytes, Chinese Medical Journal. 2009, 122(12): 1439-1443.

Researcher : Jiang L

List of Research Outputs

Jiang L., Wong G.T.C., Zhu B. and Irwin M.G., Intrathecal Morphine Postconditioning reduces cardiac ischemia reperfusion injury via central opioid receptor activation, 18th Annual Meeting of The International Society of Anaesthetic Pharmacology, New Orleans. 2009.

Wong G.T.C., Jiang L. and Irwin M.G., Activation of Central Opioid Receptors Induces Cardioprotection Against Ischemia-Reperfusion Injury , Anesthesia and Analgesia. 2009, 111(1): 24-28.

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil Post-conditioning Attenuates Cardiac Ischemia–reperfusion Injury Via Κ Or Δ Opioid Receptor Activation, Acta Anaesthesiologica Scandinavica. 2010, 54: 510-518.

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil postconditioning attenuates cardiac ischemia-reperfusion injury via kappaor delta opioid receptor activation, Acta naesthesiologia Scandinavica. 2010, 54(4): 510-518.

Researcher : Lei S

List of Research Outputs

Liu H., Liu K.X., Cheng M.H., Liu Y., Lei S., Irwin M.G. and Xia Z., Bosentan Affects 15-F2t-Isoprostane Adverse Effects on Postischemic Rat Hearts, Journal of Surgical Research. 2009, 155: in press.

Liu H., Lei S., Luo T., Xia Z.Y., Liu Y., Leung G.P.H., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., Nitroglycerin Reduces TNF- Toxicity To Endothelial Cells but Compromises the Protective Effects of Propofol, FASEB Journal. 2010, 24: 959.9.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., PKC β inhibitor ruboxistaurin prevents the increase of 15-F2tisoprostane in the myocardium and plasma in Type 1 diabetic rats, FASEB Journal . 2010, 24: 572.1.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R. and Xia Z., Ruboxistaurin attenuates hypertriglyceridemia in diabetic rats:Comparison with the antioxidant N-acetylcysteine, FASEB Journal. 2010, 24: 572.5.

Xia Z., Liu H., Xia Z.Y., Liu Y., Lei S., Mao X. and Irwin M.G., Endothelin-1 blockade with bosentan attenuates15-F2t-Isoprostane adverse effects on postischemic rat hearts, FASEB Journal . 2010, 24: 573.3.

Researcher : Li R

List of Research Outputs

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil Post-conditioning Attenuates Cardiac Ischemia–reperfusion Injury Via Κ Or Δ Opioid Receptor Activation, Acta Anaesthesiologica Scandinavica. 2010, 54: 510-518.

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil postconditioning attenuates cardiac ischemia-reperfusion injury via kappaor delta opioid receptor activation, Acta naesthesiologia Scandinavica. 2010, 54(4): 510-518.

Zhang Y., Irwin M.G., Li R., Chen Z.W. and Wong T.M., Effects of remifentanil on intracellular Ca2+ and its ransients induced by electrical stimulation and caffine inrat ventricuar myocytes, Chinese Medical Journal. 2009, 122(12): 1439-1443.

Researcher : Liman S

List of Research Outputs

Liman S., Cheung C.W. and Ng J.K.F., Serum pro-inflammatory indiced in chronic post-ischemia pain (CPIP) rat model of complex regional pain syndrome (CRPS) type I, The American Society for Clinical Investigation (ASCI)/The Association of Americal Physicians (AAP) 2010 Joing Meeting. 2010.

Researcher : Liu H

List of Research Outputs

Liu H., Liu K.X., Cheng M.H., Liu Y., Lei S., Irwin M.G. and Xia Z., Bosentan Affects 15-F2t-Isoprostane Adverse Effects on Postischemic Rat Hearts, Journal of Surgical Research. 2009, 155: in press.

Liu H., Lei S., Luo T., Xia Z.Y., Liu Y., Leung G.P.H., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., Nitroglycerin Reduces TNF- Toxicity To Endothelial Cells but Compromises the Protective Effects of Propofol, FASEB Journal. 2010, 24: 959.9.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., PKC β inhibitor ruboxistaurin prevents the increase of 15-F2tisoprostane in the myocardium and plasma in Type 1 diabetic rats, FASEB Journal . 2010, 24: 572.1.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R. and Xia Z., Ruboxistaurin attenuates hypertriglyceridemia in diabetic rats:Comparison with the antioxidant N-acetylcysteine, FASEB Journal. 2010, 24: 572.5.

Xia Z., Liu H., Xia Z.Y., Liu Y., Lei S., Mao X. and Irwin M.G., Endothelin-1 blockade with bosentan attenuates15-F2t-Isoprostane adverse effects on postischemic rat hearts, FASEB Journal . 2010, 24: 573.3.

Xia Z., Luo T., Liu H., Wang F., Xia Z.Y., Irwin M.G. and Vanhoutte P.M.G.R., L-arginine enhances nitrative stress and exacerbates tumor necrosis factor-alpha toxicity to human endothelial cells in culture: prevention by propofol, Journal of Cardiovascular Pharmacology. 2010, 55(4): 358-67.

Researcher : Liu Y

List of Research Outputs

Liu H., Liu K.X., Cheng M.H., Liu Y., Lei S., Irwin M.G. and Xia Z., Bosentan Affects 15-F2t-Isoprostane Adverse Effects on Postischemic Rat Hearts, Journal of Surgical Research. 2009, 155: in press.

Liu H., Lei S., Luo T., Xia Z.Y., Liu Y., Leung G.P.H., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., Nitroglycerin Reduces TNF- Toxicity To Endothelial Cells but Compromises the Protective Effects of Propofol, FASEB Journal. 2010, 24: 959.9.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., PKC β inhibitor ruboxistaurin prevents the increase of 15-F2tisoprostane in the myocardium and plasma in Type 1 diabetic rats, FASEB Journal . 2010, 24: 572.1.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R. and Xia Z., Ruboxistaurin attenuates hypertriglyceridemia in diabetic rats:Comparison with the antioxidant N-acetylcysteine, FASEB Journal. 2010, 24: 572.5.

Xia Z., Liu H., Xia Z.Y., Liu Y., Lei S., Mao X. and Irwin M.G., Endothelin-1 blockade with bosentan attenuates15-F2t-Isoprostane adverse effects on postischemic rat hearts, FASEB Journal . 2010, 24: 573.3.

Researcher : Liu Y

List of Research Outputs

Researcher : Lu Y

List of Research Outputs

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Interaction between spinal opioid and adenosine receptors in the remote cardiac preconditioning effect of intrathecal morphine, J of Cardiothorac Vasc Anesth. 2010, in press.

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Intrathecal Morphine Remotely Preconditions The Heart Via Multiple Neural Pathways In The Rat, 2010 Annual Scientific Meeting of the Australian and New Zealand College of Anaesthetists. 2010.

Researcher : Mao X

List of Research Outputs

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., PKC β inhibitor ruboxistaurin prevents the increase of 15-F2tisoprostane in the myocardium and plasma in Type 1 diabetic rats, FASEB Journal . 2010, 24: 572.1.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R. and Xia Z., Ruboxistaurin attenuates hypertriglyceridemia in diabetic rats:Comparison with the antioxidant N-acetylcysteine, FASEB Journal. 2010, 24: 572.5.

Xia Z., Liu H., Xia Z.Y., Liu Y., Lei S., Mao X. and Irwin M.G., Endothelin-1 blockade with bosentan attenuates15-F2t-Isoprostane adverse effects on postischemic rat hearts, FASEB Journal . 2010, 24: 573.3.

Researcher : Ng JKF

Project Title:	Effect of non-steroidal anti-inflammatory agents on platelet function and blood loss in patients undergoing major joint replacement surgery
Investigator(s):	Ng JKF, Chiu PKY, Tang WM
Department:	Anaesthesiology
Source(s) of Funding:	Queen Mary Hospital Charitable Trust - Training and Research Assistance Scheme
Start Date:	10/2007

Abstract:

To establish the correlation between PFA-100 measurement and blood loss during surgery, hopefully the results may help to establish the clinical usefulness of PFA-100 in monitoring patients with preoperative platelet dysfunction or those who are taking anti-platelet medications before surgery.

Project Title:	Lipid emulsion in resuscitation of ropivacaine cardiac toxicity in swine
Investigator(s):	Ng JKF, Leung GPH
Department:	Anaesthesiology
Source(s) of Funding:	Small Project Funding
Start Date:	09/2008
Completion Date:	02/2010

Abstract:

Local anaesthetic agents are very useful drugs in anaesthesia for the performance of regional, local or topical anaesthesia. However, local anaesthetic agents can cause severe systemic toxicity, whihc usually manifest as cardiotoxicity and is frequently fatal. (1)(2)Systemic local anaesthetic toxicity is defintely the most severe complication that can occur under regional or local anaesthesia. Systemic toxicity may occur as a result of administration of an overdose of the local anaesthetic, or due to inadvertent intravascular injection. Previously there is no antidote for systemic local anaesthetic toxicity and the condition is frequently fatal. The use of lipid in resuscitation of local anaesthetic toxicity had gained much attention recently.(3)(4) Although the exact mechanism was not well defined, some enthusiastic authors suggested that it may become our first effective antidote to this most deadly regional anesthesia complication. (1) This hypothesis was first proposed by Weinberg, who has demonstrated a shift in the dose response curve to bupivacaine induced asystole in rats.(5)(6) He then further extend the test to life dogs. Lipid infusion was able to rescue dogs suffering from bupivacaine induced cardiac toxicity.(7) Different authors have very different opinions on the whether we should extrapolate the results to human.(8)(9) The clinical efficacy was first supported by a case report published 2006. Rosenblatt and colleagues successfully rescued a patient, who developed bupivacaine related cardiac arrest, with Intralipid after apparently failed resuscitation with advanced cardiac life support protocol. (10)(11) Current evidence therfore suggests that lipid infusion is effective in treating bupivacaine induced cardiac toxicity. However, all the above studies were conducted using bupivacaine. There is no study in the current literature to show the same beneficial effect of lipid in another commonly used long acting local anaesthetic agent, ropivacaine. Ropivacaine is a newer local anaesthetic agent which has claimed some benefit over bupivacaine in terms of e.g. differential motor and sensory block. We would like to find out if Intralipid is also useful in ropivacaine induced cardiovascular toxicity. The pharmacological properties of ropivacaine are very similar to bupivacaine. Their chemical structures resemble each other. They shared the same pKa and both have very high level of protein binding (95%). Ropivacaine is marketed as pure S-isomer. It has lower lipid solubility, intrinsic vasoconstricting property and stereo-specificity which distunguishes it from bupivacaine. (12) Ropivacaine at sufficiently high plasma concentration can also cause lethal cardiotoxicity. (13) While bupivacaine and ropivaciane are similar drugs, it has also been recently demonstrated that pre-treatment with clonidine, an alpha-2 adrenergic receptor agonist, may reduce the cardiac toxicity of ropivacaine, while ineffective for bupivacaine. (14) Of course pre-treatment is not very practical clinically as what is needed is an antidote that can be used after the development of toxicity. Nevertheless, the findings of this study suggests that ropivacaine and bupivacaine cardiotoxicity may have different mechanisms. Therefore although Intralipid has previously been shown to be effective in treating bupivacaine cardiotoxicity, its efficacy in cardiotoxicity induced by ropivacaine needs to be evaluated separately. The aim of our study is to investigate the efficacy of lipid emulsion in resuscitation of ropivacaine induced cardiac toxicity. In addition, all previous studies examining the efficacy of intralipid in bupivacaine induced cardiac arrest have not included a control group which has received effective cardiopulmonary resuscitation (CPR) according to current Advance Cardiac Life Support (ACLS) guidelines. In our study, the effect of intralipid will be compared to a control group which will receive active CPR according to current guidelines. Lastly, reduced myocardial mitochondrial ATP production has been shown to be one of the cellular mechanisms of bupivacaine cardiotoxicity. (15) The effect of Intralipid treatment on ropivacaine induced cardiotoxicity and its relation to myocardial ATP will also be examined in the present study. References 1. Greensmith JE, Murray WB. Complications of regional anesthesia. Curr Opin Anesthesiol. 2006; 19: 531-7 2. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51: 285-7 3. Picard J. Lipid emulsion to treat overdose of local anaesthetic: gift of the glob. Anaesthesia 2006; 61: 107-9 4. Groban L, Butterworth J. Lipid reversal of bupivacaine toxicity: has the silver bullet been identified? Reg Anesth Pain Med 2003; 28: 167-9 5. Weinberg GL, VadeBoncouer T, Ramaraju Gopal A, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology 1998; 88:1071-5 6. Weinberg GL, Ripper R, Murphy P, Edelman LB, Hoffman W, Strichartz G, Feinstein DL. Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med 2006; 31: 296–303 7. Weinberg GL, Richard R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med 2003; 28: 198–202 8. Dalgleish D, Kathawaroo S. Lipid emulsion to treat bupivacaine toxicity. (Correspondence). Anaesthesia 2005; 60: 822. 9. Gray H. Role of intralipid in the management of local anaesthetic toxicity. (Correspondence). Anaesth Intensive Care 2006; 34: 518 10. Rosenblatt MA, Abel M, Fisher GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% Lipid Emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006; 105: 217–8 11. Weinberg G. Lipid infusion resuscitation for local anesthetic toxicity: Proof of clinical efficacy. Anesthesiology 2006; 105: 7-8 12. Langan G, McLure HA. Review of local anaesthetic agents. Curr Anaesth Crit Care. 15, 2004; 247-54 13. Groban L, Deal D D, Vernon J C. Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs. Anesth Analg 2001; 92: 37-43 14. Gulec S, Aydin Y, Uzuner K, Senturk Y. Effects of clonidine pre-treatment on bupivacaine and ropivacaine cardiotoxicity in rats. Eur J Anaesthesiol 2004; 21: 205-9. 15. DeLaCoussaye JE, Bassoul B, Albat B, et al. Experimental evidence in favor of role of intracellular actions of bupivacaine in myocardial depression. Anesth Analg 1992; 74: 698-702.

Project Title:	Effect of desmopressin on platelet dysfunction associated with mild hypothermia in healthy volunteers
Investigator(s):	Ng JKF, Cheung CW
Department:	Anaesthesiology
Source(s) of Funding:	Small Project Funding
Start Date:	12/2009

Abstract:

Mild hypothermia (34-35℃) is known to cause platelet dysfunction[1,2]. Increased surgical bleeding and increased transfusion requirement at this temperature range has been reported in both cardiac and noncardiac surgeries[3-5]. This degree of hypothermia is common during any general anaesthesia. During general anaesthesia, patients suffer from both increased heat loss and reduced heat generation. Heat loss typically occur as a result of distribution of core heat to surface following vasodilatation which acoompanies the administration of most anaesthtic agents. Large area exposure, which is required during many surgical procedures, e.g. in burn patients, will significantly aggravate this. Heat loss also occur via the respiratory tract as a result of mechanical ventilation using dry gas, via exposure to cold intravenous fluids and blood products and via impairment of the body's natural heat conservating mechanisms such as piloerection during general anaesthesia. Heat production is reduced as a result of the decrease in metabolic rate and absence of muscular activity after induction of general anaesthesia[6]. Although this hypothermia-induced platelet dysfunction seems to be reversible with warming[7,8], warming is not always possible or desirable. During major trauma or burn surgery, surface warming of patient is practically difficult. During surgeries with major blood loss and fluid shift, heat loss usually occurs at a rate that is more rapid than any warming device can catch up with. Under such circumstances, adequate warming is frequently impossible and patients can bleed excessively in the presence of hypothermia-induced platelet dysfunction. Sometimes hypothermia is induced as a therapeutic procedure. This can happen during neurosurgery when cooling may be beneficial to neurological outcome[9]. Recently, it has also been shown that induced hypothermia is beneficial for patients who has been succesfully resuscitated from a cardiac arrest[10,11]. Under such circumstances, rewarming may be undesirable and hypothermia-induced platelet dysfunction may carry risks of bleeding related morbidity and mortality[12]. Desmopressin (DDAVP) is a drug which has proven efficacy in improving platelet function in uraemic and cirrhosis patients, and in reducing blood loss in selected surgeries[13]. In a recent in vitro study, we have found that desmopressin significantly improves platelet function at 32℃[14]. However, a number of questions remain unanswered. First, in our last study, desmopressin was added in vitro. One of the major mechinsms by which desmopressin improves haemostasis is via improvement of platelet-von Willebrand factor interaction[15]. This cannot be assessed in an in vitro model where endothelial cells are not present. Moreover in this study, the improvement is seen with a very low concentration of desmopressin in vitro, which suggests that probably doses much smaller than the "standard dose" (15 mcg slow iv or subcutaneous) may be useful. We have therefore designed this study as a follow up to our last study. 1. Wolberg A et al. A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma 2004: 56: 1221-8. 2. Michelson A et al. The effects of aspirin and hypothermia on platelet function in vivo. Br J Haematol 1999; 104: 64-8. 3. Cavallini M et al. Effects of mild hypothermia on blood coagulation in patients undergoing elective plastic surgery. Plast Reconstr Surg 2005; 116: 316-21. 4. Hofer C et al. Influence of body core temperature on blood loss and transfusion requirements during off-pump coronary artery bypass grafting: A comparison of 3 warming systems. J Thorac Cardiovasc Surg 2005; 129: 838-43. 5. Schmied H et al. Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty. Lancet 1996; 347: 289-92. 6. Sessler D. Temperature monitoring and perioperative thermoregulation. Anesthesiology 2008; 109: 318-38. 7. Winkler M et al. Aggressive warming reduces blood loss during hip arthroplasty. Anesth Analg 2000; 91: 978-84. 8. Schmied H et al. The effects of red-cell scavenging, hemodilution, and active warming on allogenic blood requirements in patients undergoing HIP or knee arthroplasty. Anesth Analg 1998; 86: 387-91. 9. Todd M et al. Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med 2005; 352: 135-45. 10. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346: 549-56. 11. Bernard S et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346: 557-63. 12. Tam LK, Ng KFJ. The role of desmopressin in a patient with severe coagulopathy aggravated by mild therapeutic hypothermia [letter]. Resuscitation, in press. 13. Flordal P et al. Use of desmopressin to prevent bleeding in surgery. Eur J Surg 1998; 164: 5-11. 14. Ying CLA, Tsang SF, Ng KFJ. The potential use of desmopressin to correct hypothermia-induced impairment of primary haemostasis – An in-vitro study using PFA-100. Resuscitation 2008; 76: 129-33. 15. Mannucci P. Desmopressin: a nontransfusional form of treatment for congenital and acquired bleeding disorders. Blood 1988; 72: 1449-55.

Project Title:	Vascular effects of dexmedetomidine
Investigator(s):	Ng JKF, Leung GPH, Vanhoutte PMGR
Department:	Anaesthesiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To map out the detailed distribution of alpha2-adrenergic receptor subtypes (namely alpha2A/D, alpha2B and alpha2C) in porcine large coronary and coronary resistance arteries; 2) To study the effect of dexmedetomidine in relaxing/ contracting porcine large coronary and coronary resistance arteries; 3) To correlate the vascular effects of dexmedetomidine with the detailed distribution of alpha2-adrenergic receptor subtypes in porcine large coronary and coronary resistance arteries; 4) To study the effect of dexmedetomidine in relaxing/ contracting rat aorta and mesenteric artery under control and endotoxaemic conditions; 5) To study the mechanisms involved in the changes in vascular effects of dexmedetomidine in endotoxaemic rats.

List of Research Outputs

Liang C., Leung S.W.S., Ng J.K.F., Man R.Y.K. and Vanhoutte P.M.G.R., Endothelium-derived nitric oxide inhibits the relaxation to CNP in the porcine coronary artery, 13th Research Postgraduate Symposium, December 10-11, 2008. 2009.

Liang C., Leung S.W.S., Ng J.K.F., Man R.Y.K. and Vanhoutte P.M.G.R., Inhibition of the relaxation to CNY by endothelium-derived nitric oxide in the porcine coronary artery, Twelfth Annual Scientific Meeting of Institute of Cardiovascular Science and Medince, December 13-14, 2008, Hong Kong. 2009.

Liman S., Cheung C.W. and Ng J.K.F., Serum pro-inflammatory indiced in chronic post-ischemia pain (CPIP) rat model of complex regional pain syndrome (CRPS) type I, The American Society for Clinical Investigation (ASCI)/The Association of Americal Physicians (AAP) 2010 Joing Meeting. 2010.

Ng J.K.F., Lawmin J.C., Tsang S.F., Tang W.M. and Chiu P.K.Y., The value of a single preoperative PFA-100® measurement in assessing the risk of bleeding in patients taking cyclooxygenase inhibitors and undergoing total knee replacement, British Journal of Anaesthesia. 2009, 102: 779-84.

Researcher : Rodrigo MRC

Project Title:	4th South Asian Confederation of Anaesthesiologists Congress Anaesthesia for Orthognathic Surgery
Investigator(s):	Rodrigo MRC
Department:	Anaesthesiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	09/1999

Abstract:

N/A

Project Title:	The Association of Dental Anaesthetists 25th Anniversary Summer Scientific Meeting Patient Controlled Sedation with Propolfol
Investigator(s):	Rodrigo MRC
Department:	Anaesthesiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	06/2002

Abstract:

N/A

Researcher : Trinh TP

List of Research Outputs

Irwin M.G., Trinh T.P. and Yao C.L., Occupational exposure to anaesthetic gases - a role for TIVA, Expert Opinion in Drug Safety. 2009, 8(4): 473-483.

Researcher : Wong GTC

Project Title:	The cardiac preconditioning effect of surgery patients
Investigator(s):	Wong GTC, Irwin MG, Hiong YT, Das SR
Department:	Anaesthesiology
Source(s) of Funding:	Queen Mary Hospital Charitable Trust - Training and Research Assistance Scheme
Start Date:	10/2007

Abstract:

The aim of this study is to demonstrate a preconditioning effect of remifentanil in humans. This will be evaluated in the context of cardiac bypass surgery. It is well established that the heart would sustained some form of ischaemic damage during cardiopulmonary bypass. We hypothesize that remifentanyl when given in high doses before cardiopumonary bypass would confer some form of protection. The preconditioning effect would be evaluated by a blood test for markers of cardiac damage, cardiac performance as evaluated by haemodynamic monitoring and by echocardiography.

Project Title:	Remifentanil Postconditioning Attenuates Cardiac Ischemia-Reperfusion Injury via opioid receptors activation
Investigator(s):	Wong GTC, Irwin MG, Xia Z, Jiang L, Li R
Department:	Anaesthesiology
Source(s) of Funding:	Small Project Funding
Start Date:	08/2008
Completion Date:	07/2010

Abstract:

The purpose of the proposed project is to investigate whether remifentanil postconditioning can confer cardiac protection and to elucidate some of the mechanisms underlying this protective property. Background Preconditioning refers to an intervention which will reduce the number of cells dying and or preserve cellular function following tissue ischaemia (lack of blood supply). Opioids including the drug remifentanil have been shown to precondition the heart when administered into the bloodstream or into the central nervous system [1-3]. This effect can be blocked by the use of specific opioid receptor antagonists [4]. However, the benefits of this intervention is premised upon being able to predict the timing of the ischaemic event, which is not often achievable,. Recent research interest has been focused upon postconditioning, a phenomenon whereby an intervention administered after the start of the ischaemic event can confer protection. This has the obvious advantage of negating the need to anticipate the timing of the often unpredictable ischaemic event. Rather, the postconditioning treatment can be given immediately after the start of the ischaemic insult which is a more obvious time point. Experimentally, this effect has been demonstrated to involve opioid receptors [5], akin the opioid preconditioning.. Postconditioning by means of a series of staccato reperfusion interspersed with deliberate ischaemia, under very controlled circumstances (like in a cardiac catheterization laboratory), has been shown to reduce biochemical markers of cardiac damage and improve the long term outlook for patients suffering from an acute myocardial infarction (heart attack) [6-9]. However, postconditioning by this mechanical means has the potential to damage the blood vessels which can have devastating consequences. Further, it requires highly trained professionals with sophisticated equipment to administer. Postconditioning by pharmacological means will represent a less hazardous means that can be used more widely for myocardial salvage. The drug remifentanil can be administered intravenously and is very short acting so that it is not associated with the known prolonged side effects of other opioids such as respiratory depression. Previous work in our laboratory has demonstrated its efficacy in preconditioning the heart against ischaemic damage [10]. Key Issues • Demonstrate whether remifentanil postconditioning is protective against ischaemia reperfusion injury • Compare the magnitude of this beneficial effect with ischemic postconditioning using the same model • Determine whether this effect can be antagonised by opioid receptor antagonists • Evaluate whether this effect is a locally or systemically mediated phenomenon by using the isolated perfused heart model References 1. Murphy, G.S., et al., Opioids and cardioprotection: the impact of morphine and fentanyl on recovery of ventricular function after cardiopulmonary bypass. J Cardiothorac Vasc Anesth, 2006. 20(4): p. 493-502. 2. Kato, R., S. Ross, and P. Foex, Fentanyl protects the heart against ischaemic injury via opioidreceptors, adenosine A1 receptors and KATP channel linked mechanisms in rats. Br J Anaesth, 2000. 84(2): p. 204-14. 3. Zhang, Y., M.G. Irwin, and T.M. Wong, Remifentanil preconditioning protects against ischemic injury in the intact rat heart. Anesthesiology, 2004. 101(4): p. 918-23. 4. Zhang, Y., et al., Remifentanil preconditioning confers cardioprotection via cardiac kappa- and delta-opioid receptors. Anesthesiology, 2005. 102(2): p. 371-8. 5. Zatta AJ et al Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. American Journal of Physiology - Heart & Circulatory Physiology 2008; 294: H1444-51 6. Laskey WK et al. Brief repetitive balloon occlusions enhance reperfusion during percutaneous coronary intervention for acute myocardial infarction: a pilot study. Catheterization & Cardiovascular Interventions 2005; 65: 361-7 7. Staat P et al. Postconditioning the human heart.[see comment]. Circulation 2005; 112: 2143-8 8. Ma X et al.: Effect of postconditioning on coronary blood flow velocity and endothelial function and LV recovery after myocardial infarction. Journal of Interventional Cardiology 2006; 19: 367-75 9. Thibault H et al. Long-term benefit of postconditioning. Circulation 2008; 117: 1037-44 10. Zhang, Y., M.G. Irwin, and T.M. Wong, Remifentanil preconditioning protects against ischemic injury in the intact rat heart. Anesthesiology, 2004. 101(4): p. 918-23.

Project Title:	2010 ANZCA Annual Scientific Meeting Intrathecal Morphine Remotely Preconditions The Heart Via Multiple Neural Pathways In The Rat
Investigator(s):	Wong GTC
Department:	Anaesthesiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	05/2010
Completion Date:	05/2010

Abstract:

N/A

List of Research Outputs

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., DIFFERENTIAL EXPRESSION OF P65 AND P50 IN THE RAT'S HYPOTHALAMUS INDUCED BY CHRONIC CONSTRICTION NERVE INJURY , Third International Congress on Neuropathic pain (Athens). 2010.

Chou C.W., Wong G.T.C., Wang S., Lim G., Irwin M.G. and Mao J., Differential expression of p65 NF-κB in the rat’s brain regions induced by chronic constriction nerve injury , NeuroScience 2009 Chicago; Society for Neuroscience. 2009.

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., Spatiotemporal Pattern of Concurrent Spinal and Supraspinal NF-kappaB Expression After Peripheral Nerve Injury, Journal of Pain. 2010, 1-9.

Chou C.W., Wong G.T.C., Lim G., Wang S., Irwin M.G. and Mao J., Spatiotemporal pattern of concurrent spinal ad supraspinal NF-kappab expression after peripheral nerve injury, J Pain. 2010.

Jiang L., Wong G.T.C., Zhu B. and Irwin M.G., Intrathecal Morphine Postconditioning reduces cardiac ischemia reperfusion injury via central opioid receptor activation, 18th Annual Meeting of The International Society of Anaesthetic Pharmacology, New Orleans. 2009.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., PKC β inhibitor ruboxistaurin prevents the increase of 15-F2tisoprostane in the myocardium and plasma in Type 1 diabetic rats, FASEB Journal . 2010, 24: 572.1.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R. and Xia Z., Ruboxistaurin attenuates hypertriglyceridemia in diabetic rats:Comparison with the antioxidant N-acetylcysteine, FASEB Journal. 2010, 24: 572.5.

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Interaction between spinal opioid and adenosine receptors in the remote cardiac preconditioning effect of intrathecal morphine, J of Cardiothorac Vasc Anesth. 2010, in press.

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Intrathecal Morphine Remotely Preconditions The Heart Via Multiple Neural Pathways In The Rat, 2010 Annual Scientific Meeting of the Australian and New Zealand College of Anaesthetists. 2010.

Wong G.T.C., Jiang L. and Irwin M.G., Activation of Central Opioid Receptors Induces Cardioprotection Against Ischemia-Reperfusion Injury , Anesthesia and Analgesia. 2009, 111(1): 24-28.

Wong G.T.C., Opioid Organ Protection, Annual Scientific Meeting in Anaesthesiology. Hong Kong College of Anaesthesiology. 2009.

Wong G.T.C., Peer reviewer of manuscript, Acta Anaesthesiologica Scandinavica. 2010.

Wong G.T.C., Peer reviewer of manuscript, Hong Kong Medical Journal. 2010.

Wong G.T.C. and Irwin M.G., Pretreatment Time with Norbinaltorphimine , Anesthesia and Analgesia . 2010, 110: 1244.

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil Post-conditioning Attenuates Cardiac Ischemia–reperfusion Injury Via Κ Or Δ Opioid Receptor Activation, Acta Anaesthesiologica Scandinavica. 2010, 54: 510-518.

Wong G.T.C., Huang Z., Ji S. and Irwin M.G., Remifentanil Reduces the Release of Biochemical Markers of Myocardial Damage After Coronary Artery Bypass Surgery: A Randomized Trial , Journal of Cardiothoracic Vascular Anesthesia. 2010, 790-796.

Wong G.T.C., Li R., Jiang L. and Irwin M.G., Remifentanil postconditioning attenuates cardiac ischemia-reperfusion injury via kappaor delta opioid receptor activation, Acta naesthesiologia Scandinavica. 2010, 54(4): 510-518.

Wong G.T.C., Huang Z. and Irwin M.G., Remifntanil reduces the release of biochemical arkes of myocardial damage after coronary artery bypass surgery. A randomized trail., J Cardiothorac Vasc Anesth. 2010.

Wong G.T.C., When Pain is Inevitable, Do Words Matter, "Frontiers in Medical and Health Sciences Education - HKU 2009" Conference: Making Sense in Communication. 2009.

Researcher : Xia Z

Project Title:	Antioxidant attenuation of diabetic myocardial hypertrophy in diabetic cardiomyopathy: effects on myocardial PKC β2 overexpression
Investigator(s):	Xia Z, Irwin MG, Wong GTC, Wong TM
Department:	Anaesthesiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	02/2008
Completion Date:	10/2009

Abstract:

1. To investigate the effects and mechanisms of NAC alone or in combination with Lithospermate B (LAB), an active component isolated from Salvia Miltiorrhizae known to have antioxidant properties, on the development of cardiac hypertrophy in diabetic rats; 2. To examine if the attenuation of cardiac hypertrophy produced by the PKC inhibitor LY333531 is mediated through the reduction of oxidative stress and enhancement of NO levels, and to explore the potential synergistic or addictive effects of PKC2 inhibition and antioxidant NAC or LAB on the development of cardiac hypertrophy and cardiomyopathy in diabetic rats; 3. To determine if PKCß2 activation is necessary for hyperglycemia-induced cardiomyocyte hypertrophy and the relationship between oxidative stress and PKCß2 activation.

Project Title:	Nitrate tolerance compromises propofol protection of the endothelium against inflammation: The role of PKC-beta2 and NADPH oxidase interaction
Investigator(s):	Xia Z
Department:	Anaesthesiology
Source(s) of Funding:	SCA Research Starter and MidCareer Grants
Start Date:	07/2008

Abstract:

(1) To determine the role of PKC- ß2 in the development of nitrate tolerance in human umbilical vein endothelial cells (HUVECs) and its relationship with NADPH oxidase activation, in the absence or presence of TNF- α stimulation. (2) To determine the effects of propofol on activation of PKC isoforms and NADPH oxidase subunits in HUVECs subjected to TNF- α stimulation, in the absence or presence of nitroglycerin or L-arginine supplementation. (3) To determine if treatment with propofol in combination with the selective PKC- ß2 inhibitor CGP53353 or NADPH oxidase inhibitor apocynin can prevent nitrate tolerance and attenuate TNF- α induced endothelial injury (in HUVECs) and dysfunction in isolated rat aortic rings.

Project Title:	L-Arginine Exacerbates TNF-Alpha Toxicity in Endothelial cells and Cardiomyocytes: Role of PKC-β2 activation
Investigator(s):	Xia Z, Irwin MG, Vanhoutte PMGR
Department:	Anaesthesiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	05/2009

Abstract:

HYPOTHESES: Supplementation of L-arginine will exacerbate pro-inflammatory cytokine tumor necrosis factor-α (TNF- α) induced vascular endothelial cell and cardiomyocyte injury. It does this by activating protein kinase C-ß (PKC- ß2) and NADPH oxidase. OBJECTIVES AND SPECIFIC AIMS: The purpose of the study is 1. to determine the role of PKC- ß2 in the development of nitrate tolerance in human umbilical vein endothelial cells (HUVECs) and its relationship with NADPH oxidase activation, in the absence or presence of TNF- α stimulation. 2. to determine the role of PKC- ß2 in TNF- α induced cardiomyocyte apoptosis, in the absence or presence of L-arginine supplementation. 3. to determine if treatment with antioxidant N-acetylcysteine (NAC) in combination with the selective PKC- ß2 inhibitor CGP53353 or NADPH oxidase inhibitor apocynin can prevent nitrate tolerance and attenuate TNF- α induced endothelial injury (in HUVECs) and cardiomyocyte injury. BACKGROUND and PRELIMINARY STUDY: Endothelium and myocardial ischemia-reperfusion injury (IRI): Coronary artery disease is a leading cause of death in many countries/regions. The morbidity and mortality attendant with myocardial ischemic injury/infarction remains significant despite advancement in surgical techniques and pharmacological therapies, in part due to the increased disease severity in the elderly or in patients with diabetes. Ischemia/reperfusion injury of the heart is not limited to cardiomyocytes but also extends to coronary vascular cells, and especially the coronary endothelium 1. Of interest, circulatory pro-apoptotic inflammatory cytokines (such as tumor necrosis factor [TNF]-α) and reactive oxygen species (ROS), which are increased during myocardial IRI and atherosclerosis, may promote cardiomyocyte apoptosis subsequent to the induction of endothelial cells apoptosis 2. Thus, inhibition of TNF- α and ROS induced endothelial cell apoptosis may represent an effective therapy for myocardial IRI. We observed that the antioxidant N-acetylcysteine (NAC) reduced TNF- α induced apoptosis in primary cultured human umbilical vein endothelial cells (HUVECs) 3and further increased nitric oxide (NO) content in the culture medium following TNF- α stimulation. To determine whether the increase in NO could favor endothelial cell survival under conditions of TNF- α stimulation, we supplemented the NO synthase (NOS) substrate L-arginine (100 μM, 30 min prior to the addition of TNF- α to cultured ECV304 cells (a cell line of HUVECs origin). The result was that L-arginine further increased TNF- α (24 hr stimulation) induced endothelial cell apoptosis with concomitant increases of NO production and superoxide production as well as increase of nitrotyrosine production (preliminary observation). We postulate that the development of nitrate tolerance is a mechanism responsible for these observed adverse effects of L-arginine. Nitrate tolerance and myocardial IRI: Nitrate tolerance (NT) is a phenomenon where the clinical or hemodynamic response to organic nitrates (such as nitroglycerin) is attenuated or abolished after prolonged, continuous, or high dose nitrate treatment 4. Increased PKC and NADPH oxidase activation, eNOS uncoupling and the subsequent increase in superoxide and peroxynitrite (ONOO-, product of superoxide and NO reaction) production in the vascular endothelium have been reported to play important roles in the development of NT 4-8, resulting in impaired endothelium-dependent vasodilatation . Most recent studies conducted in human and animal blood vessels reveal that oxidative inhibition of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2) 5; 9-12, plays an important role for the development of nitrate and cross-tolerance. Of note, NT has been shown to aggravate post-ischemic myocardial apoptosis and to impair myocardial functional recovery after ischemia in animal models 13, which can be reversed by treatment with glutathione 14, an endogenous “scavenger” of peroxynitrite. In an animal study, supplementation of L-arginine, a nitric oxide precursor, during late phase of myocardial ischemia/reperfusion (MI/R) increases myocyte apoptosis and exacerbates myocardial injury 15. In humans, supplementation of L-arginine has been shown to reduce NT following nitroglycerin treatment in patients with stable angina 16. However, large randomized clinical trial results indicate that L-arginine supplementation may be associated with higher postinfarction mortality following acute myocardial infarction (AMI) 17. Interestingly, a study published in February 2008 clearly shows that the expression of TNF- α converting enzyme at the site of ruptured plaques in patients with AMI is high, accompanied with increased systemic levels of TNF- α with patients with stable angina and these levels were significant independent predictors of adverse cardiac events in AMI patients 18. So, it seems plausible that L-arginine may have aggravated postinfarction mortality in patients with AMI 17 via enhancing TNF- α toxicity, or TNF- α facilitated the development of NT, leading to enhanced cardiac mortality. This notion is supported by our preliminary results that L-arginine exacerbated TNF-α toxicity in cultured human endothelial cells (data not shown). Potential role of PKC-β2 and NADPH oxidase in TNF-- α toxicity: Activation of PKC has been shown to play a critical role in TNF- α induced human endothelial cell apoptosis 19. We further demonstrated that PKC-β2 is the isoform that plays a dominate role in mediating TNF-α endothelial toxicity. The selective PKC-β2 inhibitor CGP53353 prevented TNF-α induced increase in endothelial cell apoptosis and the increase in cellular superoxide production (data not shown). Endothelial NADPH oxidase is a major source of superoxide in blood vessels and is implicated in the oxidative stress accompanying various vascular diseases 20-22. PKC-β activation has been shown to play important or critical roles in NADPH oxidase activation 23-25. PKC-β2 is preferably up regulated in failing human hearts 26-28 which is accompanied with increased levels of TNF- α production 18; 29 and NADPH oxidase activation 30-32. Therefore, PKC-β2 and NADPH oxidase interplay may play critical roles in mediating cellular damage in situations associated with increased TNF- α production, such as AMI, heart failure, diabetes as well as during cardiac surgery using cardiopulmonary bypass. TNF- α induces cardiomyocyte apoptosis and exacerbates heart failure. TNF- α has been shown to induce cardiomyocyte apoptosis 33-35, which is associated enhanced NADPH oxidase activation and oxidative stress. TNF- α also exacerbates heart failure 36. It is yet to be determined whether PKC-β2 activation contributes to TNF- α toxicity to the cardiomyocytes, and whether supplementation of L-arginine can aggregate TNF- α toxicity to the cardiomyocytes via PKC-β2 activation.

Project Title:	American Society of Anesthesiologists Annual Meeting 2009 Isoflurane and Propofol Synergy in Reducing Myocardial Ischemia−Reperfusion Injury in patients
Investigator(s):	Xia Z
Department:	Anaesthesiology
Source(s) of Funding:	URC/CRCG - Conference Grants for Teaching Staff
Start Date:	10/2009
Completion Date:	10/2009

Abstract:

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Project Title:	Synergy between N-acetylcysteine, allopurinol and/or PKC-beta inhibition attenuates diabetic cardiomyopathy in the rat
Investigator(s):	Xia Z, Irwin MG, Rong J, Vanhoutte PMGR, Wang Y
Department:	Anaesthesiology
Source(s) of Funding:	General Research Fund (GRF)
Start Date:	01/2010

Abstract:

1) To address the mechanisms underlying and the dose-response characteristics of the effect of NAC alone or in combination with allopurinol, an xanthine oxidase inhibitor, on the development of cardiac hypertrophy in diabetic rats; 2) To examine if PKC inhibition with LY333531 (ruboxistaurin) can attenuate cardiac hypertrophy through the reduction of oxidative stress and enhancement of the bioavailability of NO, and to determine the effects of alternating antioxidant treatment (with NAC and/or allopurinol) and PKC2 inhibition on the development of hypertrophic cardiomyopathy in diabetic rats; 3) To determine if PKCß2 activation is necessary for hyperglycemia-induced cardiomyocyte hypertrophy and the relationship between oxidative stress and PKCß2 activation.

Project Title:	PKC-beta2 Over Expression in the Myocardium of Diabetic Rats Compromises Opioid Agonist-Induced Cardioprotection
Investigator(s):	Xia Z, Irwin MG, Wong GTC
Department:	Anaesthesiology
Source(s) of Funding:	Seed Funding Programme for Basic Research
Start Date:	03/2010

Abstract:

Objectives: Objective 1. To determine the role of protein kinase C (PKC) beta 2 overexperssion and the subsequent NADPH oxidase activation in delta- and/or kappa-opioid agonist mediated acute cardioprotection hearts of diabetic rats. Objective 2. To confirm the role of NADPH oxidase in opioid preconditioning induced cardioprotection will be confirmed in hearts from NADPH oxidase subunit gp91phox gene knock-out mice (gp91phox-/) subjected to coronary ligation and reperfusion. Objective 3. To determine the relative role played by gp91phox and gp22phox in opioid induced cardiac protection. Myocardial ischemia-reperfusion injury and preconditioning Myocardial reperfusion is the restoration of blood flow to an ischemic heart, which is necessary to salvage the ischemic myocardium. However, reperfusion after a prolonged period of ischemia such as after myocardial infarction or in patients undergoing cardiac surgery using cardiopulmonary bypass results in oxidative stress and is a known causative factor of injury to cardiac muscle 1-4. Myocardial reperfusion injury is also seen after the use of primary percutaneous coronary intervention following myocardial infarction and this may account for significant morbidity 5; 6. Consequently the prevention of this has recently been suggested to be an important therapeutic target 6. Brief episodes of ischemia and reperfusion given before prolonged ischemia and reperfusion protect the myocardium and are termed ischemic preconditioning (IPC). However, numerous experimental studies reveal that the cardioprotective effects of these phenomena have been suppressed in the presence of some pathological factors such as hyperglycemia and obesity (see2 for a review). On the hand, although IPC is a powerful form of protection, its clinical application is limited because of ethical and practical reasons. Of interest, pharmacological preconditioning (PPC) with agents such as opioid agonists and adenosine, can also mediate cardioprotection via mechanisms similar to that of IPC. However, opioid agonist -induced preconditioning effect is also diminished in diabetic hearts7. Hearts of diabetic patients are less tolerant to ischemia. It is therefore important to develop strategies to restore diabetic heart sensitivity to preconditioning stimuli. Role of NADPH oxidase and protein kinase C (PKC) in preconditioning Recent studies show that NADPH oxidase activation plays a beneficial role in early ischemic preconditioning and that the activity of an upstream protein kinase C (PKC) isoform (such as PKC-delta or PKC-epsilon) is critical to preconditioning triggered NADPH oxidase activity and the subsequent cardioprotection8; 9. PKC-delta 10 and PKC-epsilon 11 activate NADPH oxidase through different mechanisms that involves the up-regulation of NOX1, a catalytic subunit of NADPH oxidase. Significance and possible outcome of proposed research We have shown that the opioid agonist remifentanil confers preconditioning-like cardioprotection via both cardiac kappa- and delta opioid receptors in rat hearts 12; 13 , and that the preconditioning effects of the opioid agonists rely on the activation of PKC 14; 15. However, remifentanil’s preconditioning effect is diminished in the hearts of diabetic rats. We also found that the myocardial NADPH oxidase protein is over expressed with a resulting increased enzyme activity, and that PKC-beta2 is also over expressed in the hearts of diabetic rats. Treatment with the antioxidant N-acetylcysteine normalized these changes 16. Of interest, N-acetylcysteine treatment also restores diabetic heart sensitivity to remifentanil preconditioning (please see preliminary data). Based on these findings, we hypothesize that: 1. Moderate NADPH oxidase activation subsequent to the  and  isoforms of PKC activation plays a critical role in preconditioning by opioid agonists and the resulting cardioprotection in the normal myocardium 2. In diabetes, NADPH oxidase over expression subsequent to persistent PKC-beta2 activation compromises or cancels opioid agonist-induced cardioprotection of the myocardium The testing of these hypotheses will provide insight into the mechanisms of why the heart of diabetics is less sensitive to pharmacological preconditioning. Most importantly, results gained from the proposed studies will facilitate the development of optimal therapeutic regimens in the prevention/treatment of myocardial ischemia-reperfusion injury in patients with diabetes. Overall outline of approach: We will firstly use general and isoform specific PKC inhibitors as well as a selective NADPH oxidase inhibitor to investigate the role of PKC and NADPH oxidase in opioid agonist preconditioning and cardioprotection in non-diabetic control rats (Sprague-Dawley) subjected to 30 min coronary artery ligation and 120 min reperfusion. Further, the role of NADPH oxidase in opioid preconditioning induced cardioprotection will be confirmed in isolated hearts [Langendorff model] from NADPH oxidase subunit gp91phox gene knock-out mice (gp91phox-/) subjected to global myocardial ischemia-reperfusion. Finally, the effects of opioid preconditioning induced protection on cultured cardiac myocytes subjected to simulated ischemia (120 min) and reperfusion (120 min) will be investigated in control cells as well as in myocytes transfected with gp91phox or gp22phox antisense, respectively, to look into the relative role played by gp91phox and gp22phox in opioid induced cardioprotection.

List of Research Outputs

Li Y.S., Wang Z.X., Li C., Xu M., Li Y., Huang W.Q., Xia Z. and Liu K.X., Proteomics of Ischemia/Reperfusion Injury in Rat Intestine With and Without Ischemic Postconditioning, Journal of Surgical Research. 2009, Epub ahead of print.

Liu H., Liu K.X., Cheng M.H., Liu Y., Lei S., Irwin M.G. and Xia Z., Bosentan Affects 15-F2t-Isoprostane Adverse Effects on Postischemic Rat Hearts, Journal of Surgical Research. 2009, 155: in press.

Liu H., Lei S., Luo T., Xia Z.Y., Liu Y., Leung G.P.H., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., Nitroglycerin Reduces TNF- Toxicity To Endothelial Cells but Compromises the Protective Effects of Propofol, FASEB Journal. 2010, 24: 959.9.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R., Irwin M.G. and Xia Z., PKC β inhibitor ruboxistaurin prevents the increase of 15-F2tisoprostane in the myocardium and plasma in Type 1 diabetic rats, FASEB Journal . 2010, 24: 572.1.

Liu Y., Lei S., Liu H., Mao X., Wong G.T.C., Vanhoutte P.M.G.R. and Xia Z., Ruboxistaurin attenuates hypertriglyceridemia in diabetic rats:Comparison with the antioxidant N-acetylcysteine, FASEB Journal. 2010, 24: 572.5.

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Interaction between spinal opioid and adenosine receptors in the remote cardiac preconditioning effect of intrathecal morphine, J of Cardiothorac Vasc Anesth. 2010, in press.

Lu Y., Wong G.T.C., Xia Z. and Irwin M.G., Intrathecal Morphine Remotely Preconditions The Heart Via Multiple Neural Pathways In The Rat, 2010 Annual Scientific Meeting of the Australian and New Zealand College of Anaesthetists. 2010.

Xia Z., Liu H., Xia Z.Y., Liu Y., Lei S., Mao X. and Irwin M.G., Endothelin-1 blockade with bosentan attenuates15-F2t-Isoprostane adverse effects on postischemic rat hearts, FASEB Journal . 2010, 24: 573.3.

Xia Z. and Irwin M.G., Esmolol May Abolish Volatile Anesthetic-Induced Postconditioning By Scavenging Reactive Oxygen Species, Anesthesiology. 2009, 111(4): 1-1.

Xia Z., Grant External Reviewer, National Natural Science Foundation of China, 05/2010 (reviewed 21 grants), 2010.

Xia Z. and Irwin M.G., Isoflurane & Propofol Synergistically Reduce Post Ischemic TNF alpha Release with Cardioplumonary Bypass. Best in Show Abstract Award (Honorable Mention), International Society for Anesthetic Pharmacology, USA. 2009.

Xia Z., Huang Z., Ji S.Y., Xia Z.Y. and Irwin M.G., Isoflurane and Propofol Synergy in Reducing Myocardial Ischemia-Reperfusion Injury in Patients, Anesthesiology. 2009, 111: A285.

Xia Z., Luo T., Liu H.M., Wang F., Xia Z.Y. and Irwin M.G., L-Arginine enhances nitrative stress and exacerbates TNF-Alpha toxicity to human endothelial cells in culture: prevention by propofol, Journal of Cardiovascular Pharmacology. 2010, 54(7): 358-367.

Xia Z., Luo T., Liu H., Wang F., Xia Z.Y., Irwin M.G. and Vanhoutte P.M.G.R., L-arginine enhances nitrative stress and exacerbates tumor necrosis factor-alpha toxicity to human endothelial cells in culture: prevention by propofol, Journal of Cardiovascular Pharmacology. 2010, 55(4): 358-67.

Xia Z., Peer Reviewer, Anesthesiology, 05/2010, 2010.

Xia Z., Peer Reviewer, Biochemical Pharmacology 02/2010, 2010.

Xia Z., Peer Reviewer, Canadian Journal of Anesthesia, 01/2010, 2010.

Xia Z., Peer Reviewer, J Cellular & Molecular Medicine 03/2010, 2010.

Xia Z., Peer reviewer, Anesthesiology 02/2010, 2010.

Xia Z., Peer reviewer, Yonsei Medical Journal (South Korea), 06/2010, 2010.

Zhang J.F., Yang J.P., Wang J.H., Xia Z., Duan S.Z. and Wu Y., Role of PKCzeta translocation in the development of type 2 diabetes in rats following continuous glucose infusion. , Diabetes Metabolism Research and Reviews. 2010, 26(1): 59-70.

Researcher : Yao CL

List of Research Outputs

Irwin M.G., Trinh T.P. and Yao C.L., Occupational exposure to anaesthetic gases - a role for TIVA, Expert Opinion in Drug Safety. 2009, 8(4): 473-483.

Researcher : Yong BH

List of Research Outputs

Chan A.C.Y., Fan S.T., Lo C.M., Liu C.L., Chan S.C., Ng K.K.C., Yong B.H., Chiu A. and Lam B.K.Y., Liver transplantation for acute-on-chronic liver failure, Hepatology International. 2009, 3(4): 571-581.

Chan S.C., Lo C.M., Yong B.H., Tsui W.J.C., Ng K.K.C. and Fan S.T., Paired donor interchange to avoid ABO-incompatible living donor liver transplantation, Liver Transplantation. 2010, 16(4): 478-481.

Chan S.C., Lo C.M., Ng K.K.C., Chok K.S.H., Yong B.H. and Fan S.T., Portal inflow and pressure changes in right liver living donor liver transplantation including middle hepatic vein (Abstract), The 15th Annual International Congress of the International Liver Transplantation Society, New York City, New York, U.S.A., 8 - 11 July 2009. Liver Transplantation. 2009, 15(Suppl 7): S92.

Chung P.H.Y., Wong K.K.Y., Tam P.K.H., Chan K.L., Ng K.K.C., Chan S.C., Hui T.W.C., Yong B.H., Fan S.T. and Lo C.M., Split graft liver transplant for paediatric patients in Hong Kong, Hong Kong Journal of Paediatrics (New Series). 2009, 14: 181-185.

Researcher : Zhang Y

List of Research Outputs

Zhang Y., Irwin M.G., Li R., Chen Z.W. and Wong T.M., Effects of remifentanil on intracellular Ca2+ and its ransients induced by electrical stimulation and caffine inrat ventricuar myocytes, Chinese Medical Journal. 2009, 122(12): 1439-1443.

Researcher : Zhu B

List of Research Outputs

Jiang L., Wong G.T.C., Zhu B. and Irwin M.G., Intrathecal Morphine Postconditioning reduces cardiac ischemia reperfusion injury via central opioid receptor activation, 18th Annual Meeting of The International Society of Anaesthetic Pharmacology, New Orleans. 2009.

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