Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Sarcolemmal and mitochondrial adenosine triphosphate- dependent potassium channels: mechanism of desflurane-induced cardioprotection. Anesthesiology 2000 Jun;92(6):1731-9

Date

06/06/2000

Pubmed ID

10839925

DOI

10.1097/00000542-200006000-00033

Abstract

BACKGROUND: Volatile anesthetic-induced preconditioning is mediated by adenosine triphosphate-dependent potassium (KATP) channels; however, the subcellular location of these channels is unknown. The authors tested the hypothesis that desflurane reduces experimental myocardial infarct size by activation of specific sarcolemmal and mitochondrial KATP channels.

METHODS: Barbiturate-anesthetized dogs (n = 88) were acutely instrumented for measurement of aortic and left ventricular pressures. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle (0.9% saline) or the nonselective KATP channel antagonist glyburide (0.1 mg/kg intravenously) in the presence or absence of 1 minimum alveolar concentration desflurane. In four additional groups, dogs received 45-min intracoronary infusions of the selective sarcolemmal (HMR 1098; 1 microg. kg-1. min-1) or mitochondrial (5-hydroxydecanoate [5-HD]; 150 microg. kg-1. min-1) KATP channel antagonists in the presence or absence of desflurane. Myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.

RESULTS: Desflurane significantly (P < 0.05) decreased infarct size to 10 +/- 2% (mean +/- SEM) of the area at risk as compared with control experiments (25 +/- 3% of area at risk). This beneficial effect of desflurane was abolished by glyburide (25 +/- 2% of area at risk). Glyburide (24 +/- 2%), HMR 1098 (21 +/- 4%), and 5-HD (24 +/- 2% of area at risk) alone had no effects on myocardial infarct size. HMR 1098 and 5-HD abolished the protective effects of desflurane (19 +/- 3% and 22 +/- 2% of area at risk, respectively).

CONCLUSION: Desflurane reduces myocardial infarct size in vivo, and the results further suggest that both sarcolemmal and mitochondrial KATP channels could be involved.

Author List

Toller WG, Gross ER, Kersten JR, Pagel PS, Gross GJ, Warltier DC

Author

Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Anesthetics, Inhalation
Animals
Benzamides
Decanoic Acids
Dogs
Glyburide
Hemodynamics
Hydroxy Acids
Hypoglycemic Agents
Ischemic Preconditioning, Myocardial
Isoflurane
Mitochondria
Myocardial Infarction
Myocardium
Potassium Channel Blockers
Potassium Channels
Regional Blood Flow
Sarcolemma
jenkins-FCD Prod-387 b0ced2662056320369de4e5cd5f21c218c03feb3