Sarcolemmal and mitochondrial adenosine triphosphate- dependent potassium channels: mechanism of desflurane-induced cardioprotection.

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.

• Authors: W G Toller, E R Gross, J R Kersten, P S Pagel, G J Gross, D C Warltier
• Journal: Anesthesiology (Anesthesiology) Vol. 92 Issue 6 Pg. 1731-9 (Jun 2000) ISSN: 0003-3022 [Print] United States
• PMID: 10839925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anesthetics, Inhalation
• Benzamides
• Decanoic Acids
• Hydroxy Acids
• Hypoglycemic Agents
• Potassium Channel Blockers
• Potassium Channels
• 5-hydroxydecanoic acid
• Adenosine Triphosphate
• HMR 1098
• Desflurane
• Isoflurane
• Glyburide

Topics

• Adenosine Triphosphate (metabolism, physiology)
• Anesthetics, Inhalation (antagonists & inhibitors, pharmacology)
• Animals
• Benzamides (pharmacology)
• Decanoic Acids (pharmacology)
• Desflurane
• Dogs
• Glyburide (pharmacology)
• Hemodynamics (drug effects)
• Hydroxy Acids (pharmacology)
• Hypoglycemic Agents (pharmacology)
• Ischemic Preconditioning, Myocardial
• Isoflurane (analogs & derivatives, antagonists & inhibitors, pharmacology)
• Mitochondria (metabolism)
• Myocardial Infarction (pathology, prevention & control)
• Myocardium (pathology)
• Potassium Channel Blockers
• Potassium Channels (agonists, metabolism)
• Regional Blood Flow
• Sarcolemma (metabolism)