Selective contractile dysfunction of left, not right, ventricular myocardium in the SHHF rat

1 Institute of Molecular Cardiobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; and 2 Department of Physiology and Cell Biology and 3 Dorothy M. Davis Heart and Lung Institute, Ohio State University, Columbus, Ohio 43210 The progression of hypertension to cardiac failure involves systemic changes that may ultimately affect contractility throughout the heart. Spontaneous hypertensive heart failure (SHHF) rats have depressed left ventricular (LV) function, but right ventricular (RV) dysfunction is less well characterized. Ultrathin (87 ± 5 µm) trabeculae were isolated from end-stage failing SHHF rats and from age-matched controls. Under near-physiological conditions (1 mM Ca 2+ , 37°C, 4 Hz), developed force (in mN/mm 2 ) was not significantly different in SHHF LV and RV trabeculae and those of controls. SHHF LV preparations displayed a negative force-frequency behavior (40 ± 7 vs. 23 ± 4 mN/mm 2 , 2 vs. 7 Hz); this relationship was positive in SHHF RV preparations (27 ± 5 vs. 40 ± 6 mN/mm 2 ) and controls (32 ± 6 vs. 44 ± 9 mN/mm 2 ). The response to isoproterenol (10 6 M, 4 Hz) was depressed in SHHF LV preparations. The inotropic response to hypothermia was lost in SHHF LV trabeculae but preserved in SHHF RV trabeculae. Intracellular calcium measurements revealed impaired calcium handling at higher frequencies in LV preparations. We conclude that in end-stage failing SHHF rats, RV function is only marginally affected, whereas a severe contractile dysfunction of LV myocardium is present. contractile function; excitation-contraction coupling; heart failure; inotropic agents; hypertension