MECHANICAL AND STRUCTURAL CORRELATES OF CONTRACTURE INDUCED BY METABOLIC BLOCKADE IN CARDIAC-MUSCLE FROM THE RAT

We performed morphological studies of myocardial contracture to define its nature and relationship to mechanical changes occurring during metabolic blockade. Isolate rat papillary and trabecular muscles were stretched to the apices of their length-tension curves and stimulated to contract isometrically 12 times a minute at a temperature of 28°C. Incomplete and total metabolic blockade were induced by 1 hour of hypoxia (95% N2, 5% CO2) or by hypoxia plus glycolytic blockade with iodoacetic acid, 10-4 M, respectively. In oxygenated control preparations, mechanical performance was stable for the 60-minute experimental period. In preparations exposed to hypoxia, developed tension fell to 7 ± 2% of prehypoxia values at 60 minutes. Contracture tension increased progressively to 2.5 ± 0.4 g/mm2. With total metabolic blockade, developed tension declined to zero by 10 minutes, contracture tension rose to an average peak value of 5.3 ± 0.4 g/mm2 by 15 minutes, and subsequently slowly declined. All preparations were fixed at L(max) in the muscle bath. Light and electron microscopic studies revealed focal irregularities of A.I. and Z bands with sarcomere malalignment, hypercontraction, and fiber disruption, which increased in severity with increasing metabolic blockade. Linear densities appeared in mitochondria following total metabolic blockade, but mitochondria appeared normal otherwise. Thus, myocardial contracture after metabolic blockade is a focal process beginning within the sarcomere; morphological alterations in the contractile apparatus correlate with mechanical changes and are more severe than those in the mitochondria.