Myocardial contractile efficiency and oxygen cost of contractility are preserved during transition from compensated hypertrophy to failure in rats with salt-sensitive hypertension.

In Dahl-Iwai rats, salt-sensitive hypertension causes concentric left ventricular hypertrophy (LVH) at the age of 11 weeks, which is followed by LV dilatation with global hypokinesis and pulmonary congestion, ie, LV failure (LVF), at 16 to 18 weeks of age. To address the question of whether the cardiac remodeling from LVH to LVF is associated with modulations of mechanoenergetic properties, we serially measured the LV pressure-volume area (PVA) and myocardial oxygen consumption (MVO2) in isolated, isovolumically contracting hearts from this animal model. The end-systolic pressure-volume relationships obtained by stepwise changes of the LV volume were fit into a binominal regression model, which provided a value of LV contractility (E(es)) and a volume intercept (V0). A slope (the reciprocal of the LV contractile efficiency) and a PVA-independent MVO2 were determined by a regression analysis of the MVO2-PVA relation. The procedure was repeated at different Ca2+ concentrations in perfusate to estimate the oxygen cost of contractility (dMVO2/dE(es)). The MVO2 was further evaluated during K+-induced cardiac arrest to delineate the basal metabolism, which was independent of the E-C coupling. During the transition from LVH to LVF, the E(es) was decreased by 50% (from 681 to 338 mm Hg x g x mL(-1), P<.001), which was associated with a substantial increase in V0 (from 0.002 to 0.07 mL, P<.01). These alterations in both the inotropic state and the ventricular shape were associated with a 45% decrease in the PVA-independent MVO2 (from 800 to 440 mL O2 x beat(-1) x g(-1), P<.01). Despite these marked changes between the two stages, both the LV contractile efficiency and the oxygen cost of contractility remained unchanged. The MVO2 during cardiac arrest also showed an equal level among the groups; hence, from LVH to LVF, the nonmechanical O2 consumption by the E-C coupling decreased in a manner parallel to the basal contractile state. We conclude that (1) in this animal model, the heart failure transition is associated with a marked decrease in myocardial contractility and with ventricular remodeling; (2) despite these changes, the efficiency of the chemomechanical conversion is highly preserved; and consequently, (3) the total energy consumption per unit of failing myocardium is diminished along with its reduced nonmechanical energy expenditure for E-C coupling. These mechanoenergetic properties might constitute an adaptive mechanism in the energy-starved condition of chronically diseased myocardium.