Morphine administration at reperfusion fails to improve postischaemic
cardiac function but limits myocardial injury probably via heat-shock
protein 27 phosphorylation
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. Eur J
Anaesthesiol 26:572-581 (C) 2009 European Society of Anaesthesiology