Overview

This dissertation, Remifentanil Induces Delayed Cardioprotection in the Rat Against Ischaemic and Reperfusion Injury via Kappa, Delta, Mu Opioid Receptorsand Inducible Heat Shock Protein 70 by Che-kwan, Yu, 俞治均, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of the thesis entitled Remifentanil induces delayed cardioprotection in the rat against ischaemic and reperfusion injury via Kappa, delta, mu- opioid receptors and inducible heat shock protein 70 submitted by Mr. Yu Che Kwan for the Degree of Master of Philosophy at The University of Hong Kong in August, 2007 Remifentanil has attractive pharmacokinetic characteristics that lead to extensive use in clinical anaesthesia. Opioid drugs are known to induce both acute and delayed cardioprotection in animal studies and this is a concept that would be highly desirable in the clinical setting. Remifentanil preconditioning (RPC) provides acute cardioprotection and this effect appears to be mediated by all three types of opioid receptors, and via protein kinase C (PKC) and mitochondrial ATP-sensitive potassium channels (K ). It was hypothesized that remifentanil also confers delayed ATP cardioprotection via opioid receptors involving several signalling proteins in the downstream pathway. Six series of experiments were conducted to address 1) whether remifentanil confers delayed cardioprotection in vivo, 2) whether in vitro pretreatment of adult rat ventricular myocytes with remifentanil could also induce a delayed cardioprotection. 3) the time course of the delayed cardioprotective effect of RPC 4) the involvement of opioid receptors in triggering delayed RPC, 5) the involvement of inducible heat shock protein 70 (HSP 70) and/or constitutively expressed heat shock protein 70 (HSC 70) in the downstream signalling pathway of RPC. 6) the 2+ involvement of remifentanil in attenuating intracellular calcium ion ([Ca ] ) overload during sustained ischaemia and reperfusion The first important observation of this study is that remifentanil significantly reduced the size of myocardial infarction at four different doses of remifentanil (1, 5, -1 -1 10, 20 mcg-kg -min ) in intact rat without a dose dependent relationship. The maximal reduction in infarct size was seen in 24 hours but was also significant at 12h, -1 -1 16h, 32h and 36h after remifentanil (10 mcg-kg -min ), disappearing at 48h after first preconditioning stimulus. The second main finding was that the cardioprotective effect of delayed RPC was abolished or significantly attenuated by co-administration of kappa (κ), mu (μ) and delta (δ) - opioid receptor antagonists while ischaemic preconditioning (IPC) was only attenuated by blockade of κ or μ - opioid receptors. The third observation was that RPC was mediated by the upregulation of either HSP 70 or HSC 70 in the rat heart. HSP 70 was upregulated at 4 hours, but not at 2 hours after sustained ischaemia and reperfusion. This time course of HSP 70 upregulation correlates with the infarct sparing effect seen at 4 hours after sustained ischaemia and reperfusion in vivo. Finally, intravenous administration of remifentanil protected the ischaemic 2+ 2+ heart from [Ca ] overload via retaining a normal [Ca ] homeostasis during lethal i i 2+ stimulated ischemia and reperfusion through monitoring the [Ca ] transient of remifentanil pretreated single ventricular myocyte during the ischaemia and reperfusion In conclusion, remifentanil produces delayed cardioprotection at four different doses of remifentanil without a doses dependant relationship in anaesthetized rats 12 to 36

Full Product Details

9781361420065

Table of Contents

Reviews

Author Information

Tab Content 6

Customer Reviews

Recent Reviews

Countries Available