AN ANIMAL-MODEL OF DILATED CARDIOMYOPATHY - CHARACTERIZATION OF DIHYDROPYRIDINE RECEPTORS AND CONTRACTILE PERFORMANCE

Broad-Breasted White turkey poults exhibit a low incidence of dilated cardiomyopathy (DCM). Ejection fraction in DCM turkeys with moderate t o severe dilatation was decreased from 67 +/- 5% (control, n = 20) to 42 +/- 4% (DCM, n = 12; P = 0.001). Moderate to severe DCM hearts demo nstrated peak left ventricular pressure 67 +/- 4 mmHg (n = 11) vs. 156 +/- 9 mmHg (n = 10; P < 0.0001). With moderate to severe dilatation, there was normal calcium responsiveness in saponin-skinned fiber exper iments. (+)[methyl-H-3]-PN200-110 binding early in the course of cardi ac dilatation was increased 62% (B(max) = 1,798 +/- 212 fmol/mg protei n, n = 9 vs. control B(max) = 1,113 +/- 48 fmol/mg, n = 26; P < 0.0001 ). The concentration to reach 50% effect (EC50) for nifedipine contrac tile response was 0.5 log unit higher for isolated DCM muscle vs. cont rol at the early stage of dilatation, consistent with the increase in calcium channel number identified by ligand binding. However, more adv anced heart failure resulted in a decrease in number of DHP binding si tes by 24% compared with control and by 53% compared with the early di lated group (B(max), moderate dilatation = 844 +/- 71 fmol/mg, n = 7; P < 0.05). Finally, with gross dilatation, there was a second increase in calcium channel number by 40% (B(max) severe dilatation = 1,556 +/ - 201 fmol/mg, n = 7; P < 0.01) compared with control, which is an inc rease of 84% vs. moderate dilatation. There are complex changes in abu ndance of calcium channels during progression of the disease that may play a role in the pathophysiology of the failing heart.