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 cha nges in electrical properties and morphology of the failing heart of Syrian cardiomyopathic hamsters (TO2) were investigated at different stages of th e pathological process, and the possible role of the renin-angiotensin syst em was studied. Cardiomyopathic hamsters 2 and 11 months of age were used. Age-matched normal hamsters (F1B) were utilized as controls. Measurements o f membrane potential, conduction velocity and refractoriness were made with conventional intracellular electrodes connected to a high impedance DC amp lifier. Serum and cardiac angiotensin-converting enzyme (ACE) activities we re 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 pot ential performed in the isolated right ventricle of 2-month old Syrian card iomyopathic hamsters indicated an average value of -66.7 +/- 0.96 mV (n = 2 5); 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 repolariz ation in 2-month old hamsters was well above the controls. The conduction v elocity measured in the isolated right ventricle of 2-month old Syrian card iomyopathic 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 t he heart of controls at 2 months of age and did not change with age. Althou gh 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 my opathic animals at 11 months of age, the enzyme activity (0.56 +/- 0.027 nm ol/mg x min) was greater than controls (P < 0.05). The ACE activity in plas ma followed the same pattern. The conclusion from these experiments is, tha t some parameters like resting potential, action potential duration, and mo rphological abnormalities appeared quite early in the failing process. The decline in conduction velocity, however, appeared later on, concurrently wi th the activation of plasma and cardiac renin-angiotensin systems. (C) 1999 Elsevier Science B.V. All rights reserved.