Comparative mammal model of chronic rate overload: relationship of myocardial Ca-cycling to heart, metabolic and lipoperoxidation rates.

1. The cardiac cycle is generally believed to be timed by a sarcoplasmic Ca-cycle and powered by a sarcoplasmic ATP-cycle that uses fatty acids as fuel and generates toxic free radicals as a side-product. 2. This study used a comparative mammal approach to test this model and the hypothesis that these cycles were closely coupled and correlated with fatty acid oxidation and peroxidative injury. 3. Fatty acid oxidation and ATP-cycling rates correlated to log heart rate whereas Ca-cycling rate was directly coupled to heart rate in a one-to-one relationship. 4. Both Ca-pump and Ca-channel activities coordinately increased as heart rate increased across species. 5. Thus, Ca-cycling activity is constant across mammals, when normalized to heart rate. 6. Comparison of Ca-ATPase and Ca-flux rates indicated that sarcoplasmic volume was inversely correlated with log heart rate. Basal lipoperoxidation of myocardium and susceptibility of SR to lipoperoxidation correlated with metabolic rate. 7. We identified that the horse is a metabolic outlier amongst mammals, with abnormally high fatty acid oxidation and ATP-synthetase activity compared to its heart rate.