Association of Depressed Myofibrillar Adenosine Triphosphatase and Reduced Contractility in Experimental Heart Failure

Abstract

Although previous studies have suggested a depression of myofibrillar ATPase in the presence of heart failure, their interpretation has been limited by failure to exclude mitochondrial contamination and lack of information regarding the contractility of the tissue studied. To explore this fundamental question, myofibrils were prepared from the right and left ventricles of 15 normal cats, 10 cats with right ventricular hypertrophy and 19 with right ventricular hypertrophy and right ventricular failure, the latter groups following graded pulmonary artery stenosis. The contractility of these hearts was assessed using their right ventricular papillary muscles isolated in a myograph. Myofibrillar ATPase in all groups was maximally activated by 5 mM ATP, 5 mM MgCl₂ at pH 7.0 and 37°C, while mitochondrial contamination was eliminated by sodium azide. In right ventricular failure, right ventricular myofibrillar ATPase was depressed by 39% from an average of 0.18±0.01 in normal cats to 0.11±0.01 µmole inorganic phosphate/mg protein per min (P<.001). In right ventricular hypertrophy, right ventricular myofibrillar ATPase was not significantly depressed (0.16±0.01 µmole/mg per min). Of note, left ventricular myofibrillar ATPase was also significantly (P<.05) depressed in right ventricular failure from 0.16±0.01 to 0.13±0.01 µmole/mg per min. Contractility of the associated right ventricular papillary muscles, expressed as maximum rate of force development at the apex of the length-active tension curve, was correlated with myofibrillar ATPase activity.