Activation of Adenosine-Monophosphate–Activated Protein Kinase Abolishes Desflurane-Induced Preconditioning Against Myocardial Infarction In Vivo

• Published in: Journal of cardiothoracic and vascular anesthesia 2011-02, Vol.25 (1), p.66-71
• Main Authors: Lotz, Christopher, MD, Fisslthaler, Beate, PhD, Redel, Andreas, MD, Smul, Thorsten M., MD, Stumpner, Jan, MD, Pociej, Joanna, BSc, Roewer, Norbert, MD, PhD, Fleming, Ingrid, PhD, Kehl, Franz, MD, PhD, DEAA, Lange, Markus, MD
• Format: Article
• Language: English
• Subjects: adenosine-monophosphate-activated protein kinase; Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - pharmacology; AMP-Activated Protein Kinases - metabolism; Anesthesia & Perioperative Care; anesthetic-induced preconditioning; Anesthetics, Inhalation - therapeutic use; Animals; Body Temperature - drug effects; cardioprotection; Cardiotonic Agents; Critical Care; desflurane; Electrocardiography - drug effects; Enzyme Activation; Glycogen - metabolism; Hemodynamics - drug effects; Hypoglycemic Agents - pharmacology; Immunoprecipitation; Ischemic Preconditioning, Myocardial; Isoflurane - analogs & derivatives; Isoflurane - therapeutic use; Male; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardium - enzymology; Myocardium - pathology; Rabbits; Ribonucleotides - pharmacology
• ISSN: 1053-0770; 1532-8422
• DOI: 10.1053/j.jvca.2010.02.007

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 < 0.05) compared with the control group (61.6% ± 3.0%), concomitant with increased myocardial tissue levels of glycogen (2.09 ± 0.07 μg, p < 0.05). Activation of the AMPK by AICAR alone did not protect against ischemic injury (65% ± 3.3), but did abolish the cardioprotection elicited by desflurane (61.8% ± 4.2%) at the same time as increasing myocardial glycogen consumption (1.42 ± 0.15 μg/mL). Conclusions The results obtained show that the pharmacologic activation of AMPK abolishes cardioprotection elicited by desflurane.