LACK OF STEREOSPECIFIC EFFECTS OF ISOFLURANE AND DESFLURANE ISOMERS IN ISOLATED GUINEA-PIG HEARTS

Background: Volatile anesthetics alter membrane channel proteins. It i s controversial whether they act by nonspecifically perturbing lipid m embranes or by directly binding to amphiphilic and usually stereoselec tive regions on channel macromolecules. Biologically relevant receptor s are usually stereoselective. The stereochemical effect of isoflurane and desflurane can be used as a pharmacologic tool to investigate whe ther these drugs bind to specific target sites. The specific optical i somers of Isoflurane and desflurane were used to examine whether they produce any differential effects on electrical, mechanical, and metabo lic function in isolated hearts. Methods: Isolated guinea-pig hearts w ere 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 in to a preoxygenated, sealed bottle of perfusate, which gave concentrati ons of 0.28 and 0.57 mM for isoflurane and 0.48 and 0.88 mM for desflu rane, which are equivalent to 1 and 2 MAC multiples. Results: Both iso mers of isoflurane and desflurane decreased left ventricular pressure, heart rate, and percent oxygen extraction and increased atrioventricu lar conduction time, coronary now, and oxygen delivery. Each change wa s significantly different from control at each concentration, and thes e 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 calc ulated variable. Also, the effects of the stereoisomers were similar t o those of the racemic mixture. Conclusion: These data indicate that t he optical isomers of isoflurane and desflurane are equipotent, as ass essed by their effects on cardiac function in isolated guinea-pig hear ts. 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 inter action at nonstereoselective sites on channels modulating cardiac anes thetic effects.