Myocardial cross-bridge kinetics in transition to failure in Dahl salt-sensitive rats

The role of altered cross-bridge kinetics during the transition from cardia c hypertrophy to failure is poorly defined. We examined this in Dahl salt-s ensitive (DS) rats, which develop hypertrophy and failure when fed a high-s alt diet (HS). DS rats fed a low-salt diet were controls. Serial echocardio graphy disclosed compensated hypertrophy at 6 wk of HS, followed by progres sive dilatation and impaired function. Mechanical properties of skinned lef t ventricular papillary muscle strips were analyzed at 6 wk of HS and then during failure (12 wk HS) by applying small amplitude (0.125%) length pertu rbations over a range of calcium concentrations. No differences in isometri c tension-calcium relations or cross-bridge cycling kinetics or mechanical function were found at 6 wk. In contrast, 12 wk HS strips exhibited increas ed calcium sensitivity of isometric tension, decreased frequency of minimal dynamic stiffness, and a decreased range of frequencies over which cross b ridges produce work and power. Thus the transition from hypertrophy to hear t failure in DS rats is characterized by major changes in cross-bridge cycl ing kinetics and mechanical performance.