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  • Title: Morphine administration at reperfusion fails to improve postischaemic cardiac function but limits myocardial injury probably via heat-shock protein 27 phosphorylation.
    Author: Mourouzis I, Saranteas T, Perimenis P, Tesseromatis C, Kostopanagiotou G, Pantos C, Cokkinos DV.
    Journal: Eur J Anaesthesiol; 2009 Jul; 26(7):572-81. PubMed ID: 19359990.
    Abstract:
    BACKGROUND AND OBJECTIVES: We explored the effects of morphine administration during reperfusion period after an index ischaemia as well as potential molecular mechanisms underlying this response. This is of important clinical value, as morphine is used routinely in cardiovascular anaesthesia and in the emergency management of cardiac infarction. METHODS: Male Wistar rat hearts, mounted on constant flow isolated Langendorff preparation, were subjected to stabilization, 30 min of zero-flow global ischaemia and 45 min of reperfusion (CONT; n = 10). Morphine (10(-6) mol l(-1)) was administered only at reperfusion (MORPH; n = 10). Postischaemic recoveries of left ventricular developed pressure were expressed as percentage of the initial value. At the end of the experimental protocol, lactate dehydrogenase release in the perfusate was measured and the left ventricle was isolated and used for determination of oxidized actin, mitogen-activated protein kinase activation and heat-shock protein 27 phosphorylation. RESULTS: Left ventricular developed pressure percentage did not differ between groups, whereas lactate dehydrogenase release was significantly reduced in MORPH compared with CONT hearts. Left ventricular developed pressure percentage was negatively correlated with lactate dehydrogenase release in CONT hearts (r = -0.8, P = 0.006), whereas in MORPH hearts no correlation was found (r = -0.2, P = 0.57). Phosphorylated p38 mitogen-activated protein kinase, c-jun N-terminal protein kinases, extracellular signal-regulated kinases and Akt at 45 min of reperfusion were similar between groups. However, a 1.5-fold increase in phospho-heat-shock protein 27 was found in MORPH hearts compared with CONT hearts (P < 0.05). Additionally, the ratio of oxidized actin to total actin was found to be 1.9-fold more in MORPH compared with CONT hearts (P < 0.05). CONCLUSION: Morphine administration at reperfusion does not affect cardiac function but limits the extent of myocardial injury, possibly through increased heat-shock protein 27 phosphorylation.
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