Faculty Collaboration Database

Lack of stereospecific effects of isoflurane and desflurane isomers in isolated guinea pig hearts. Anesthesiology 1994 Jul;81(1):129-36

Date

07/01/1994

Pubmed ID

8042781

DOI

10.1097/00000542-199407000-00019

Scopus ID

2-s2.0-0028335746 (requires institutional sign-in at Scopus site)   32 Citations

Abstract

BACKGROUND: Volatile anesthetics alter membrane channel proteins. It is controversial whether they act by nonspecifically perturbing lipid membranes or by directly binding to amphiphilic and usually stereoselective regions on channel macromolecules. Biologically relevant receptors are usually stereoselective. The stereochemical effect of isoflurane and desflurane can be used as a pharmacologic tool to investigate whether these drugs bind to specific target sites. The specific optical isomers of isoflurane and desflurane were used to examine whether they produce any differential effects on electrical, mechanical, and metabolic function in isolated hearts.

METHODS: Isolated guinea-pig hearts were perfused with Krebs-Ringer's solution containing, in random order, both isomers of either isoflurane (n = 11) or desflurane (n = 6) for 10 min with a 15-min washout period. Either anesthetic was injected into a preoxygenated, sealed bottle of perfusate, which gave concentrations of 0.28 and 0.57 mM for isoflurane and 0.48 and 0.88 mM for desflurane, which are equivalent to 1 and 2 MAC multiples.

RESULTS: Both isomers of isoflurane and desflurane decreased left ventricular pressure, heart rate, and percent oxygen extraction and increased atrioventricular conduction time, coronary flow, and oxygen delivery. Each change was significantly different from control at each concentration, and these effects were greater with the high compared to the low concentration of each anesthetic. There was no significant difference between the (+)- and the (-)-isomers for either anesthetic for any measured or calculated variable. Also, the effects of the stereoisomers were similar to those of the racemic mixture.

CONCLUSIONS: These data indicate that the optical isomers of isoflurane and desflurane are equipotent, as assessed by their effects on cardiac function in isolated guinea-pig hearts. Although both agents may ultimately influence hydrophilic domains of the protein channels, their major cardiac effect appears to result either from global perturbation of the membrane lipids and/or an interaction at nonstereoselective sites on channels modulating cardiac anesthetic effects.

Author List

Graf BM, Boban M, Stowe DF, Kampine JP, Bosnjak ZJ

Authors

Zeljko Bosnjak PhD, MS Emeritus Professor in the Medicine department at Medical College of Wisconsin
David F. Stowe PhD, MA, MA Emeritus Professor in the Anesthesiology department at Medical College of Wisconsin

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

Animals
Atrioventricular Node
Coronary Circulation
Depression, Chemical
Guinea Pigs
Heart
Heart Rate
In Vitro Techniques
Isoflurane
Myocardial Contraction
Myocardium
Oxygen Consumption
Stereoisomerism
Ventricular Function, Left