ESTIMATION OF NONMECHANICAL VO(2) IN ISOLATED RABBIT HEART - COMPARISON OF MECHANICAL UNLOADING AND BDM METHOD

To understand the mechaneoenergetics of heart muscle, it is important to be able to accurately partition energy consumption into its two maj or components, that used for nonmechanical activity [mainly excitation -contraction (E-C) coupling and basal metabolism] and that used for me chanical activity (cross-bridge cycling). In most experiments in the b eating heart, this has been accomplished by assuming that the unloaded oxygen consumption (VO2) represents nonmechanical VO2 and subtracting it from total VO2 to yield mechanical Vet. However, unloaded VO2 is ' 'contaminated'' by an uncertain amount of energy consumption for cross -bridge cycling under unloaded conditions. We recently reported an alt ernative method to estimate nonmechanical VO2 using the negative inotr opic drug 2,3-butanedione monoxime (BDM), which, in theory, should not include cross-bridge cycling-related energy consumption. In the prese nt study, we compared changes in unloaded VO2 and the BDM estimate of nonmechanical VO2 as E-C coupling was varied by changing the perfusate Ca2+ concentration ([Ca2+]) in the isolated rabbit heart. An isolated , red blood cell-perfused, isovolumically contracting balloon in left ventricle preparation was employed. In one group (n = 8), contractilit y (maximal elastance), unloaded VO2, and the BDM estimate of nonmechan ical VO2 were assessed at a perfusate [Ca2+] of 2.5 mM and then at 5.0 mM. In a second group (n = 6), perfusate was 1.0 and 2.5 mM. The chan ge in contractility in each group as [Ca2+] was increased was comparab le. Unloaded VO2 was systematically greater than the BDM estimate of n onmechanical VO2 under all conditions. However, the absolute change in both estimates was similar in both groups. In conclusion, over the ra nge of perfusate [Ca2+] employed in this study, changes in unloaded VO 2 and the BDM estimate of nonmechanical VO2 are similar. These results support the use of unloaded VO2, which is easier to measure and has l ess estimation error in individual cases than the BDM-derived value fo r nonmechanical VO2, as an accurate index of change in E-C coupling en ergy consumption.