ULTRASTRUCTURAL AND ELECTROPHYSIOLOGICAL ALTERATIONS DURING THE DEVELOPMENT OF CATECHOLAMINE-INDUCED CARDIAC-HYPERTROPHY AND FAILURE

Cardiac hypertrophy and failure were induced in male Wistar rats by daily administration of 5 mg/kg isoproterenol for three weeks. Age-matched animals were used as normal control. To estimate the degree of hypertrophy, the wet heart weight (HW) to body weight (BW) ratio (HW/BW) was used as an index of the myocardial enlargement. By the 7th day of the treatment, the HW/BW ratio was increased to 4.24, as compared with the control value of 3.11. In this early stage of cardiomyopathy, the structure was characterized with small necrotic foci, enlarged myofilaments and swollen mitochondria. The electrical activity showed braodened action potentials with an elevated plateau phase, and increased membrane resistance and time constant. The amplitude of the twitch contractions was elevated. Continuing the treatment of the animals with catecholamine caused a decompensated heart failure by the 21st day. In this late stage, many and large necrotic foci could be observed in the myocardium. The mitochondria were fragmented, and the resistance of the sarcolemma decreased, and the electrical and contractile activity suppressed. The results indicate that an electrically and structurally compensated cardiac hypertrophy model can be produced by a short-term treatment of the animals with isoproterenol, while a long-term treatment causes a decompensated heart failure.