Diminished cardiac hypertrophy and muscle performance in older compared with younger adult rats with chronic atrioventricular block.

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Abstract
The combined effect of advancing age and hemodynamic overload on cardiac muscle function has received little attention. In male, Sprague-Dawley rats, we studied the interaction of chronic atrioventricular heart block induced by transvenous electrocautery for 4-12 months (mean, 7 months) and age at study (12, 19 +/- 0.7, and 24 +/- 0.2 months) on cardiac hypertrophy and muscle function compared with age-matched, sham-operated controls. Hypertrophy was determined by the ratio of heart weight to tibial length. Muscle function was first determined from the mechanical variables of the isometric contraction of an excised, thin, left ventricular trabecular muscle bathed at 29 degrees C under a variety of calcium concentrations and stimulation patterns. Then, in the same muscles after disruption of membranes with Triton X-100, the force-pCa curve of the myofibrils was obtained. No hypertrophy occurred with aging in the control group, but alteration in hypertrophy with age occurred in the block group such that the youngest animals with block had the most hypertrophy (170%) and the oldest animals with block the least hypertrophy (120%). The tension developed by cardiac muscle and the duration of the isometric contraction were not affected by age in the control group but were significantly affected by age in the block group. The young animals with block had a markedly prolonged contraction duration and almost twice the developed tension compared with the older animals with block or with controls. The age-related difference in muscle contraction duration in the block group was associated with, and may have only been secondary to, the age-related difference in the extent of cardiac hypertrophy. For developed tension, the age-related difference in the block group could not be explained by differences in the extent of cardiac hypertrophy. Rather, this difference was attributable to both an increased myofibrillar force-generating capacity in the young block and to an impairment in excitation-contraction coupling in the old block. The results show that during long-term block, age exerted not only a significant effect on the extent of cardiac hypertrophy but also an independent effect on the developed tension of cardiac muscle.