Related Experiment Videos
Hypoperfusion-induced contractile failure does not require changes in cardiac energetics
K W Saupe1, F R Eberli, J S Ingwall
1Cardiac Muscle Research Laboratory, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Insights
Reduced blood flow to the heart immediately impairs function, but not due to energy depletion. Non-energetic factors, not changes in cardiac energetics, dominate initial contractile dysfunction during hypoperfusion.
Area of Science:
- Cardiology
- Biochemistry
- Physiology
Background:
- Decreased coronary perfusion leads to rapid loss of heart muscle function.
- Cardiac energetics (energy production and use) are suspected to cause this dysfunction.
- The precise cause of this immediate contractile dysfunction remains unclear.
Purpose of the Study:
- To investigate if changes in cardiac energetics precede the decline in contractile function.
- To determine the causal relationship between energy metabolism and heart muscle function during reduced blood flow.
- To identify the primary drivers of contractile dysfunction during myocardial hypoperfusion.
Main Methods:
- Utilized 14 isolated rat hearts for the study.
- Gradually reduced coronary perfusion in a controlled manner.
- Employed 31P NMR spectroscopy to measure key energy metabolites (ATP, PCr, Pi, ADP), pH, and free energy from ATP hydrolysis (|DeltaGATP|).
Main Results:
- No significant changes in ATP, PCr, ADP, or pH were observed until several minutes after systolic pressure decreased.
- Even with a significant drop in developed pressure, changes in Pi, pH, and |DeltaGATP| were minimal.
- The rate of high-energy phosphate transfer did not decrease sufficiently to account for the observed loss of contractile function.
Conclusions:
- Non-energetic factors are the primary cause of initial systolic dysfunction during decreased myocardial perfusion.
- Cardiac energetics do not appear to be the dominant factor in the immediate contractile dysfunction.
- The study challenges the long-held hypothesis linking ischemia-induced changes in cardiac energetics to immediate contractile dysfunction.
Abstract:
Decreasing coronary perfusion causes an immediate decrease in contractile function via unknown mechanisms. It has long been suspected that this contractile dysfunction is caused by ischemia-induced changes in cardiac energetics. Our goal was to determine whether changes in cardiac energetics necessarily precede the contractile dysfunction as one would expect if a causal relationship exists. In 14 isolated rat hearts, we gradually decreased coronary perfusion using a coronary perfusate with a normal hematocrit and normal concentrations of the major metabolic substrates. Using 31P NMR spectroscopy to measure ATP, phosphocreatine (PCr), Pi, and ADP concentrations ([ATP], [PCr], [Pi], [ADP]), pH, and amount of free energy released from ATP hydrolysis (|DeltaGATP|), we found that none of these variables changed significantly until several minutes after systolic pressure had significantly decreased. Even when developed pressure had decreased by over one-third, only very slight changes in [Pi], pH, and |DeltaGATP| had occurred, with no significant changes in [ATP], [PCr], or [ADP]. Additionally, the rate of high-energy phosphate transfer between ATP and PCr did not decrease enough during hypoperfusion to explain the contractile dysfunction. We conclude that nonenergetic factors are the dominant cause of the initial decrease in systolic function when myocardial perfusion is decreased.