Artificial selection for whole animal low intrinsic aerobic capacity co-segregates with hypoxia-induced cardiac pump failure.

Oxygen metabolism is a strong predictor of the general health and fitness of an organism. In this study, we hypothesized that a divergence in intrinsic aerobic fitness would co-segregate with susceptibility for cardiovascular dysfunction. To test this hypothesis, cardiac function was assessed in rats specifically selected over nineteen generations for their low (LCR) and high (HCR) intrinsic aerobic running capacity.

Parvalbumin gene delivery improves diastolic function in the aged myocardium in vivo.

Abnormal relaxation of the heart, termed diastolic dysfunction, is a significant and growing problem that is a major cause of heart failure in the aged population. The potential of gene transfer of parvalbumin (Parv), a cytoplasmic calcium-binding protein, to improve diastolic function in the aged myocardium in vivo was evaluated. Despite evidence for an early developmental influence on the efficiency of Ad5 striated muscle transduction, results show that Ad5 gene transfer efficiency to adult cardiac myocytes in vitro is identical in young and old rats, suggesting that the basic processes of adenovirus binding and internalization are unaffected by aging.

Targeting diastolic dysfunction by genetic engineering of calcium handling proteins.

Diastolic heart failure (HF) is associated with significant morbidity and mortality, and is a growing medical problem in this country. Diastolic dysfunction is defined as an abnormality in myocardial relaxation that impairs filling during diastole and contributes to the clinical syndrome of HF. Effective clinical strategies to treat diastolic dysfunction are limited.