ENERGETICS OF THE NEGATIVE AND POSITIVE INOTROPISM OF PENTOBARBITAL SODIUM IN THE CANINE LEFT-VENTRICLE

Objective: Pentobarbitone (sodium) is an anaesthetic widely used in animal experiments. It is known to be a cardiovascular depressant and a coronary dilator, but its effects on myocardial energetics in relation to its negative and positive (due to Gregg's phenomenon) inotropism have not been studied. The aim of this study was therefore to determine whether and how pentobarbitone affects cardiac mechanoenergetics compared with other negative inotropic agents for which data are already available. Methods: The effects of graded doses of intracoronary pentobarbitone on mechanoenergetics were studied in the excised cross circulated left ventricles of 12 dogs. The framework of the E(max) (a contractility index) - Vo(2) (myocardial oxygen consumption) - PVA (systolic pressure-volume area, a measure of total mechanical energy) relationships was fully utilised. Results: Pentobarbitone increased E(max) at low doses in five of the 12 hearts. In two of these five hearts, a marked coronary dilatation was found. Pentobarbitone decreased E(max) dose dependently at high doses in all the hearts and lowered the Vo(2) intercept but not the slope (oxygen cost of PVA) of the Vo(2)-PVA relation. There was no difference in oxygen cost of E(max) between pentobarbitone and CaCl2, although they have opposite inotropism. These findings suggest that pentobarbitone depresses myocardial mechanoenergetics via suppression of total calcium handling in the excitation-contraction-relaxation coupling. Conclusions: Pentobarbitone at low doses partly acts as a positive inotropic agent, but at high doses it acts as a negative inotropic agent like beta blockers and calcium antagonists on cardiac mechanoenergetics in canine blood perfused hearts.