The reorganization of the human and rabbit heart in response to haemodynamic overload
N R Alpert1, G Hasenfuss, L A Mulieri
1Department of Physiology and Biophysics, University of Vermont, Burlington 05405.
Insights
Heart failure involves altered cross-bridge cycling and reduced calcium cycling, impacting heart muscle economy and function. These changes are linked to specific protein alterations, not myosin isoforms.
Area of Science:
- Cardiovascular Physiology
- Biophysics
- Cardiac Muscle Mechanics
Background:
- Heart failure is characterized by impaired cardiac function.
- Understanding the underlying mechanisms of cardiac muscle contraction and relaxation is crucial for developing effective treatments.
- Myothermal and mechanical analyses provide insights into the energetic and mechanical properties of heart muscle.
Purpose of the Study:
- To investigate the alterations in cross-bridge cycling and calcium handling in failing human hearts and pressure-overloaded rabbit hearts.
- To partition heat production into tension-dependent and tension-independent components to understand energy utilization.
- To correlate mechanical and energetic changes with alterations in calcium cycling and transport proteins.
Main Methods:
- Myothermal and mechanical analysis of non-failing and failing human hearts.
- Analysis of normal and pressure-overloaded rabbit hearts.
- Measurement of heat production, force, and calcium cycling.
- Partitioning of heat production into tension-dependent and independent components.
Main Results:
- Failing human hearts and pressure-overloaded rabbit hearts exhibit increased cross-bridge force-time integral, indicating greater economy but reduced velocity and power.
- Calcium cycling is significantly reduced in failing human hearts and pressure-overloaded rabbit hearts compared to their respective controls.
- Alterations in cross-bridge cycling may be related to isoenzyme shifts in light chains or troponin T, and calcium cycling changes correlate with alterations in calcium transport proteins.
Conclusions:
- Altered cross-bridge cycling and calcium handling are key contributors to the functional deficits in heart failure.
- Changes in contractile and excitation-contraction coupling systems play a significant role in the pathophysiology of heart failure.
- The findings suggest potential therapeutic targets related to calcium transport and contractile protein regulation.
Abstract:
A myothermal/mechanical analysis on non-failing and failing human hearts and normal and pressure overloaded rabbit hearts is reported. Heat production is partitioned into tension-dependent and tension-independent components together with force measurements to provide information about calcium and cross-bridge cycling. In the non-failing human heart the cross-bridge force-time integral is 0.51 +/- 0.06 (ns). This value is increased to 0.97 +/- 0.09 (P less than 0.05 s) in failing hearts. In control as compared to pressure-overload rabbit hearts the cross-bridge force-time integral increases from 0.36 +/- 0.02 to 0.96 +/- 0.11 (P less than 0.05 s). The increase in force-time integral allows the heart muscle to develop force with greater economy (less high energy phosphate hydrolysis) but at the expense of velocity and power. The amount of calcium cycled following activation in non-failing human hearts is 32.2 +/- 8.17 nmoles.g-1.-beat-1. In the failing preparations calcium cycling is reduced to 16.7 +/- 1.72 nmoles.g-1.-beat-1. In pressure-overloaded hypertrophied, as compared with control rabbit hearts, the calcium cycled per beat is reduced from 43.0 +/- 7.3 to 17.6 +/- 3.4 nmoles.g-1. It is suggested that the alterations in cross-bridge cycling are more likely to be related to isoenzyme shifts in light chains or troponin T than to myosin isoforms. The calcium cycling changes are well correlated with changes in the sarcoplasmic reticular and sarcolemmal calcium transport proteins. The alterations in the contractile and excitation contractions coupling systems contribute to the functional changes observed in the failing human and pressure-overload rabbit hearts.
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