Differential effects of cardiac hypertrophy and failure on right versus left ventricular calcium activation

Abstract

We studied calcium responsiveness of skinned muscle preparations from the right and left ventricles of rats with cardiac hypertrophy and cardiac hypertrophy plus failure. To test the hypothesis that differences in contractile function are due to changes in myofilament calcium responsiveness, we compared preparations from spontaneously hypertensive rats with cardiac failure, spontaneously hypertensive rats without cardiac failure, and age-matched normotensive Wistar-Kyoto control rats 18-24 months of age. Rats with failure had pleural/pericardial effusions, left atrial thrombi, and right and left ventricular hypertrophy. Muscles were skinned by saponin (250 micrograms/ml) and activated with a series of calcium buffers. Data were plotted as pCa (-log[Ca2+]) versus isometric force and then fit to a modified Hill equation. Values for 50% maximal activation (calcium sensitivity), maximal calcium-activated force, and the slope of the calcium-force relation were compared. Our data indicate that with the development of hypertrophy, calcium sensitivity of left ventricular muscles remains unaffected, but maximal calcium-activated force is increased. In contrast, maximal calcium-activated force declines toward control levels with the development of left ventricular failure, despite the continued presence of significant hypertrophy. In the normotensive rats, the left ventricle is more sensitive to calcium than the right ventricle (pCa50 = 6.0 +/- 0.05 versus 5.7 +/- 0.09; p less than 0.05); however, both the calcium sensitivity and maximal calcium-activated force of the right ventricle increase with the development of compensatory hypertrophy secondary to left ventricular failure. These changes that occur in rats with cardiac hypertrophy and failure may represent important physiological adaptive mechanisms.