Activation of adenosine-monophosphate-activated protein kinase abolishes desflurane-induced preconditioning against myocardial infarction in vivo.

Objectives Myocardial ischemia is accompanied by a rapid activation of adenosine-monophosphate–activated protein kinase (AMPK). However, it is unclear whether this represents a potentially beneficial or detrimental event in the course of ischemic injury. The role of AMPK activation in the cardioprotective setting of desflurane-induced preconditioning has not been investigated to date. Hence, the current study was undertaken to address the role of AMPK activation during desflurane-induced preconditioning in vivo. Design A prospective randomized vehicle-controlled study. Setting A university research laboratory. Subjects Male New Zealand white rabbits (n = 44). Interventions The animals were subjected to a 30-minute coronary artery occlusion (CAO) followed by 3 hours of reperfusion. Desflurane (1.0 minimum alveolar concentration) was administered for 30 minutes and discontinued 30 minutes prior to CAO. Different groups of animals received the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-riboside (AICAR), alone or in combination with desflurane. Infarct size was determined gravimetrically; AMPK activity and myocardial glycogen content were measured using specific assays. Phosphorylation of the AMPK substrate, acetyl-CoA carboxylase, was assessed by immunoblotting. Data are mean ± standard error of the mean. Results Desflurane significantly reduced the myocardial infarct size (36.7 ± 1.9%, p p Conclusions The results obtained show that the pharmacologic activation of AMPK abolishes cardioprotection elicited by desflurane.