SODIUM PENTOBARBITAL VERSUS ALPHA-CHLORALOSE ANESTHESIA - EXPERIMENTAL PRODUCTION OF SUBSTANTIALLY DIFFERENT SLOPES IN THE TRANSMURAL CP ATP RATIOS WITHIN THE LEFT-VENTRICLE OF THE CANINE MYOCARDIUM

Background Transmural analyses of the creatine phosphate (CP)/ATP rati o in various lamina of the canine myocardium have previously revealed significant variations in the CP/ATP ratio, with the subendocardial la yer displaying a decreased ratio relative to the subepicardial layer. Without exception, these results were obtained under sodium pentobarbi tal anesthesia. These findings have been interpreted to imply that the normal endocardium may be operating in the oxygen-limited domain or t hat there are transmurally varying set points for the regulation of ox idative phosphorylation. Methods and Results In this work, we examine the effect of the anesthetic regimen on the transmural CP/ATP ratio wi thin the left ventricular wall of the canine myocardium using spatiall y localized P-31-nuclear magnetic resonance (NMR) and an open-chest mo del. Two anesthetics were compared, alpha-chloralose and sodium pentob arbital. Under sodium pentobarbital, the CP/ATP ratio ranged from 1.92 +/-0.06 to 2.51+/-0.08 from endocardium to epicardium, resulting in a transmural slope in the CP/ATP ratio of 0.149+/-0.047 (n=22). Under ar -chloralose, CP/ATP ratios ranged from 2.18+/-0.05 to 2.32+/-0.06, wit h a transmural slope of 0.035+/-0.018 (n=38). Thus, the transmural slo pe in CP/ATP ratio was nearly four times greater with sodium pentobarb ital than with alpha-chloralose, and the difference in these slopes wa s statistically significant (P=.029). No difference was observed in av erage CP/ATP obtained from the entire wall with either anesthetic. Con clusions These results demonstrate that the transmural trend in CP/ATP ratio previously reported in the myocardium is likely to be a direct reflection of the sodium pentobarbital anesthetic regimen, not truly r eflecting the trend in the normal unanesthetized animal. Moreover, sin ce the transmural variation in CP/ATP ratio was greatly reduced with a lpha-chloralose, it appears unlikely that the endocardium in the norma l unanesthetized heart is operating in the oxygen-limited domain. Thes e results also point to the importance of the anesthetic regimen in bi ochemical analysis, indicate the necessity of increased caution in dir ectly translating results obtained under anesthesia, and demonstrate t he unique power of in vivo NMR to extract such subtle biochemical info rmation.