This study of impaired myocardial energetics contains four major findings. The summary is as follows:
- Myocardial energetic dysfunction in a rat model of hypertrophy and decompensation is driven by a depletion of cytoplasmic adenine nucleotide and creatine metabolic pools and by reduced production of oxidative ATP.
- Consistent with the hypothesis that changes in ATP, ADP, inorganic phosphate associated with decompensation and failure have direct roles in impeding contractile function of the myocardium in heart failure, the degree of metabolic dysfunction is predictive of the degree of mechanical dysfunction.
- Computer modeling of coupled myocardial energetics and mechanics informed by these data predicts that since ATP synthesis is stimulated by both ADP and inorganic phosphate levels, the reduced adenine nucleotide pool causes an increase in inorganic phosphate in failing hearts compared to healthy controls. Increased phosphate, in turn, impairs the kinetics of myosin ATPase cross-bridge cycling in the heart, causing systolic dysfunction.
- Computer simulations further predict that mechanical function in heart failure can be reversed by restoring phosphate metabolites to levels observed in healthy heart muscle.
Read the full article, “Impaired myocardial energetics causes mechanical dysfunction in decompensated failing hearts,” published ahead of print in Function. Contact the APS Communications Office or call 301.634.7314 to schedule an interview with a member of the research team.
