Cor pulmonale in Tsk mice with genetic emphysema : a morphological and biochemical study

The right ventricular changes which precede and accompany the spontaneous development of right ventricular hypertrophy were studied in Tsk mice with genetic emphysema. As in humans, cor pulmonale in Tsk mice is a slowly evolving process that develops late in life. The appearance of right ventricular hypertrophy was preceded by an early adaptive phase characterized by an dramatic increase in mitochondrial volume density in cardiocytes and by an enhanced turnover of contractile proteins (+35%) In this phase an augmented collagen synthesis (89%) led to an increased deposition of the more compliant type III collagen. Right ventricular hypertrophy started to develop in Tsk mice of eight months of age (i.e. seven months after the appearance of emphysema) and was accompanied by progressive normalization of mitochondrial volume density, by a relative increase in tensile type I collagen, and by appearance of “tunnel capillaries”. These data indicate that the cardiomyocyte adaptive changes are matched by a remodelling of connective tissue matrix to confer a more compliant or a more stress-tolerant network before or after appearance of the right ventricular hypertrophy.