Ultrastructural analysis of left ventricular hypertrophy in rabbits

Ultrastructural changes resulting from gradual aortic constriction were quantitated in a model for cardiac hypertrophy. Gradual aortic stenosis was produced in rabbits by swelling of an Ameroid clip. Ultrastructural, biochemical and physiological changes were observed for each heart. The ultrastructure of mitochondria in hypertrophied but non-failing hearts was normal. The respiratory activity of mitochondria isolated from these same hearts was increased. Profiles of granular endoplasmic reticulum and free ribosomes, widening of Z bands and distortions of intercalated discs were observed in hypertrophied hearts and were interpreted as evidence of synthesis of new functional components. However, different cell components increased disproportionately. Morphometric analysis revealed significant decreases in mitochondrial fractional volume (0.35 ± 0.01, P < 0.001) and mitochondria/myofibril ratios (0.59 < 0.02, P < 0.001). The results suggest that increased work load may induce a further deleterious change in the ratio between mitochondrial units and myofibril units with may lead to decompensation and failure. The ultrastructural changes observed in this model may be of interest since the model closely mimics the gradual onset of the hypertrophic response in humans.