Isoflurane-induced myocardial preconditioning is dependent on phosphatidylinositol-3-kinase/Akt signalling
Department of Anesthesiology and Critical Care Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
* Corresponding author: Department of Anesthesiology and Critical Care Medicine, Hadassah University Hospital, Jerusalem 91120, Israel. E-mail: gozaly{at}md2.huji.ac.il
Background. Isoflurane and other volatile anaesthetics have a cardioprotective effect and limit myocardial infarct size to the same extent as ischaemic preconditioning. Phosphatidylinositol-3-kinase (PI3K) was found to play a key role in myocardial protection by ischaemic preconditioning. The aim of the present investigation was to evaluate whether isoflurane-induced myocardial preconditioning is dependent on PI3K signalling.
Methods. Using a model of regional myocardial ischaemia and reperfusion, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia followed by 120 min of reperfusion. The rabbits were randomly assigned to one of the following six experimental groups: sham-operated controls (n=5); ischaemia and reperfusion controls (n=8); isoflurane preconditioning (n=8); a PI3K inhibitor, wortmannin (0.6 mg kg–1 i.v.) + isoflurane (n=8); and wortmannin+ischaemia and reperfusion (n=8). An additional control group of sham operation+ wortmannin (n=5) was also included. Myocardial injury was assessed by measuring the serum concentration of the MB fraction of creatine kinase (CK-MB) and infarct size was assessed by 2,3,5-triphenyl tetrazolium chloride staining. Phosphorylation of Akt, a downstream target of PI3K, was assessed by western blotting.
Results. Isoflurane preconditioning was seen as reduced infarct size compared with control animals: 24 (4) and 41 (5)% respectively (P<0.05). Wortmannin inhibited this cardioprotective effect with myocardial infarct size at 44 (3)% (not significant). Akt phosphorylation was increased after isoflurane preconditioning, but administration of wortmannin blocked this effect.
Conclusions. Our data demonstrate that isoflurane protects the heart against ischaemia and decreases myocardial infarction by activation of PI3K.
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