Correlation between changes in morphology, electrical properties, and angiotensin-converting enzyme activity in the failing heart

Evidence is available that morphologic and electrophysiologic abnormalities are present in the failing heart. In the present work, the progressive changes in electrical properties and morphology of the failing heart of Syrian cardiomyopathic hamsters (TO2) were investigated at different stages of the pathological process, and the possible role of the renin-angiotensin system was studied. Cardiomyopathic hamsters 2 and 11 months of age were used. Age-matched normal hamsters (F1B) were utilized as controls. Measurements of membrane potential, conduction velocity and refractoriness were made with conventional intracellular electrodes connected to a high impedance DC amplifier. Serum and cardiac angiotensin-converting enzyme (ACE) activities were measured in controls and cardiomyopathic animals. The results indicated that interstitial fibrosis and calcification were present in the heart of 2-month old Syrian cardiomyopathic hamsters. Measurements of the resting potential performed in the isolated right ventricle of 2-month old Syrian cardiomyopathic hamsters indicated an average value of -66.7 +/- 0.96 mV (n = 25); in the controls of the same age was -78.5 +/- 1 mV (n = 25, P < 0.05); and in Ii-month old cardiomyopathic hamsters was - 67.8 +/- 0.83 mV (n = 10). The duration of the action potential measured at 50 and 90% of repolarization in 2-month old hamsters was well above the controls. The conduction velocity measured in the isolated right ventricle of 2-month old Syrian cardiomyopathic hamsters (44.2 +/- 1.6 cm/s, n = 12) was not different from the control (43.7 +/- 1.1 cm/s, n = 7, P > 0.05) but was significantly larger than that recorded from the ventricle of Ii-month old animals (37.8 +/- 2.9 cm/s, n = 11, P < 0.05). ACE activity was 0.26 +/- 0.01 nmol/mg x min in the heart of controls at 2 months of age and did not change with age. Although in the 2-month old cardiomyopathic hamsters the enzyme activity (0.28 +/- 0.04 nmol/mg x min) was not different from the controls (P > 0.05), in myopathic animals at 11 months of age, the enzyme activity (0.56 +/- 0.027 nmol/mg x min) was greater than controls (P < 0.05). The ACE activity in plasma followed the same pattern. The conclusion from these experiments is, that some parameters like resting potential, action potential duration, and morphological abnormalities appeared quite early in the failing process. The decline in conduction velocity, however, appeared later on, concurrently with the activation of plasma and cardiac renin-angiotensin systems. (C) 1999 Elsevier Science B.V. All rights reserved.