Lack of stereospecific effects of isoflurane and desflurane isomers in isolated guinea pig hearts.
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.
Graf
B M
BM
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Boban
M
M
Stowe
D F
DF
Kampine
J P
JP
Bosnjak
Z J
ZJ
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D000077335:Desflurane; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013237:Stereoisomerism; D016277:Ventricular Function, Left / Q000187:drug effects
D000077335:Desflurane; D007530:Isoflurane