Estimation of nonmechanical VO2 in isolated rabbit heart: comparison of mechanical unloading and BDM method
Higashiyama, A.; Watkins, M.W.; Chen, Z.; LeWinter, M.M.
American Journal of Physiology 273(2 Pt 2): H1032-H1037
1997
ISSN/ISBN: 0002-9513 PMID: 9277524 Document Number: 475970
To understand the mechaneoenergetics of heart muscle, it is important to be able to accurately partition energy consumption into its two major components, that used for nonmechanical activity (mainly excitation-contraction (E-C) coupling and basal metabolism) and that used for mechanical activity (cross-bridge cycling). In most experiments in the beating heart, this has been accomplished by assuming that the unloaded oxygen consumption ( ovrhdot V-O-2) represents nonmechanical ovrhdot V-O-2 and subtracting it from total ovrhdot V-O-2 to yield mechanical ovrhdot V-O-2. However, unloaded ovrhdot V-O-2 is "contaminated" by an uncertain amount of energy consumption for cross-bridge cycling under unloaded conditions. We recently.reported an alternative method to estimate nonmechanical ovrhdot V-O-2 using the negative inotropic drug 2,3-butanedione monoxime (BDM), which, in theory, should not include cross-bridge cycling-related energy consumption. In the present study, we compared changes in unloaded ovrhdot V-O-2 and the BDM estimate of nonmechanical ovrhdot V-O-2 as E-C coupling was varied by changing the perfusate Ca-2+ concentration ((Ca-2+)) 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), contractility (maximal elastance), unloaded ovrhdot V-O-2, and the BDM estimate of nonmechanical V ovrhdot V-O-2 were assessed at a perfusate (Ca-2+) 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 change in contractility in each group as (Ca-2+) was increased was comparable. Unloaded ovrhdot V-O-2 was systematically greater than the BDM estimate of nonmechanical ovrhdot V-O-2 under all conditions. However, the absolute change in both estimates was similar in both groups. In conclusion, over the range of perfusate (Ca-2+)) employed in this study, changes in unloaded ovrhdot V-O-2 and the BDM estimate of nonmechanical ovrhdot V-O-2 are similar. These results support the use of unloaded ovrhdot V-O-2, which is easier to measure and has less estimation error in individual cases than the BDM-derived value for nonmechanical ovrhdot V-O-2, as an accurate index of change in E-C coupling energy consumption.