Decreased contractile efficiency and increased nonmechanical energy cost in hyperthyroid rabbit heart. Relation between O2 consumption and systolic pressure-volume area or force-time integral

Abstract

Both systolic pressure-volume area (PVA) and force-time integral (FTI) have been used as measures of oxygen consumption per beat (V̇O2) in the isolated left ventricle. The reciprocal of the slope of the V̇O2-PVA relation has been considered to reflect the chemomechanical energy transduction efficiency of the contractile machinery (contractile efficiency), whereas its V̇O2 intercept consists of energy cost of excitation-contraction coupling and basal metabolism. To examine whether the increase in myosin isoform V1/V3 ratio in hyperthyroid rabbits decreases contractile efficiency and to determine overall mechanisms of higher oxygen consumption in hyperthyroid hearts, the V̇O2-PVA and V̇O2-FTI relations as well as the end-systolic pressure-volume relation were assessed in cross-circulated, isovolumically beating hearts isolated from normal, hyperthyroid, and hypothyroid rabbits. Normalized initial slopes of the rising limb of the curvilinearity fitted end-systolic pressure-volume relation (E'(max), ventricular contractility index) were similar for normal and hyperthyroid groups. However, the slopes and V̇O2 intercepts of the V̇O2-PVA and V̇O2-FTI relations were greater in hyperthyroid hearts than in normal hearts. Accordingly, in the hyperthyroid hearts, the contractile efficiency (27 ± 6%) was lower and left ventricular V̇O2 for excitation-contraction coupling (0.028 ± 0.004 ml O2/beat/100 g) was higher than in normal hearts (40 ± 4% and 0.021 ± 0.005 ml O2/beat/100 g, respectively). This decreased contractile efficiency in the hyperthyroid hearts was attributable to myosin isoform alteration rather than to increased β-adrenoceptors because isoproterenol did not affect the slope of the V̇O2-PVA relation in all groups. In contrast, the slope of the V̇O2-FTI relation was significantly increased by isoproterenol in all groups. Neither the V̇O2-PVA nor the V̇O2-FTI relations in hypothyroid hearts were different from those in normal hearts except for significantly lower V̇O2 for basal metabolism. We conclude that in hyperthyroid rabbits, the left ventricle has decreased contractile efficiency and increased energy cost of excitation-contraction coupling and that the decreased contractile efficiency in hyperthyroid hearts is probably due to the increased V1/V3 ratio of the myosin isoform component. In addition, this study demonstrates that the V̇O2-PVA and V̇O2-FTI relations dissociate depending on the innervation, even in the same isovolumic contraction mode.