The goal of the proposed research is to better understand partitioning of energy input and the efficiency of energy utilization int he isolated, supported left ventricle (LV). In the first portion of the proposed work, we will study a new approach to partition VO2 into that used for crossbridge cycling and that used for other purposes by using the drug 2,3- butanedione monoxime (BDM). At relatively low concentration, this drug selectively inhibits crossbridges cycling. The relationship between VO2 and pressure-time integral as low-dose BDM is administered will be employed to estimate force-independent VO2 [the VO2 used for )excitation-contraction coupling + resting metabolism)]. Force-dependent VO2, or that used for crossbridge cycling, equals total VO2 minus force-independent VO2. To calculate efficiency, contractile machinery. Efficiency is thus PVA force-dependent VO2. Using this approach, the relation between force- independent VO2 and LV volume will be determined, as will the influence of load on efficiency. IN the second portion of the proposed work, the effect on OV2 partitioning and contractile efficiency of three positive inotropic interventions will be assessed. The interventions include isoproterenol, which increases crossbridge cycling rate, cooling the heart, which decreases crossbridge cycling rate, and increased perfusate calcium concentration, which does not affect crossbridge cycling rate. WE predict that the efficiency of the contractile machinery will be inversely related to the rate of crossbridge cycling. This work constitutes a new approach toward understanding energetics in the intact LV. It is anticipated that the new knowledge gained will eventually be useful in understanding the effect of acute and chronic stress on the efficiency of energy utilization by the heart.
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