Progressive loss of myocardial ATP due to a loss of total purines during the development of heart failure in dogs - A compensatory role for the parallel loss of creatine

Background-Whether myocardial ATP content falls in heart failure is a long- standing and controversial issue. The mechanism(s) to explain any decrease in ATP content during heart failure have not been identified. Methods and Results-Cardiac dysfunction, heart failure, and a prolonged ste ady state of heart failure were induced by chronic right ventricular pacing for 1 to 2 weeks, 3 to 4 weeks, and 7 to 9 weeks in dogs. Cardiac function and myocardial O-2 consumption (MVo(2)) were measured with the dogs in the conscious state. ATP, total purine, and creatine were measured in biopsy s pecimens obtained at each stage. ATP and the total purine pool progressivel y fell at rates of 0.12 and 0.15 nmol mg protein(-1).d(-1), despite an incr ease in MVo(2). The rate of loss of creatine was 1.06 nmol mg protein(-1).d (-1), 7 times faster than the depletion of total purine. Conclusions-(1) ATP contents progressively decreased during heart failure a s a result of a loss of the total purine pool. The loss of purines may be d ue to inhibition of de novo purine synthesis, (2) Loss of creatine is an ea rly marker of heart failure and mmay serve as a compensatory mechanism mini mizing the reduction of the total purine pool in the failing heart.