Related Experiment Videos
Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal
G Hasenfuss1, L A Mulieri, E M Blanchard
1Department of Physiology and Biophysics, College of Medicine, University of Vermont, Burlington.
Insights
Myocardial performance is altered in overloaded hearts, but not due to myosin changes. The crossbridge force-time integral, not myosin isoenzymes, influences energy turnover and cardiac function across species.
Area of Science:
- Cardiovascular Physiology
- Biophysics
Background:
- Myocardial hypertrophy and atrophy are linked to myosin isoenzyme composition in animals.
- Human hypertrophied hearts show altered performance without significant myosin changes, a discrepancy needing investigation.
Purpose of the Study:
- Investigate the discrepancy in myocardial performance and myosin isoenzymes between animal models and human hearts.
- Determine the relationship between crossbridge behavior, myocardial performance, and energy turnover across different species and conditions.
Main Methods:
- Isometric heat and force measurements were performed on human, rabbit, and rat myocardium.
- Studied control, volume-overload, pressure-overload, hyperthyroid, and hypothyroid conditions.
- Calculated the force-time integral of the crossbridge cycle using myothermal techniques.
Main Results:
- Volume-overload human myocardium showed reduced peak tension and increased crossbridge force-time integral.
- Hormonally altered myocardium correlated crossbridge force-time integral with V3-type myosin, unlike hemodynamically altered myocardium.
- Significant correlations were found between tension rise/fall rates and heat rates, inversely related to the crossbridge force-time integral.
Conclusions:
- Factors other than myosin isoenzymes alter the crossbridge cycle in hemodynamically overloaded human and rabbit myocardium.
- Changes in excitation-contraction coupling accompany crossbridge cycle alterations across species.
- The crossbridge force-time integral is a key determinant of myocardial energy turnover.
Abstract:
Alteration in crossbridge behavior and myocardial performance have been associated with myosin isoenzyme composition in animal models of myocardial hypertrophy or atrophy. In the hypertrophied human heart, myocardial performance is altered without significant changes in myosin isoenzymes. To better understand this discrepancy, isometric heat and force measurements were carried out in 1) control and volume-overload human myocardium, 2) control, pressure-overload, and hyperthyroid rabbit myocardium, and 3) control and hypothyroid rat myocardium. In control human myocardium, peak isometric twitch tension was 44.0 +/- 11.7 mN/mm2, and maximum rate of tension rise was 69.2 +/- 21.0 mN/sec.mm2. In volume-overload human myocardium, peak twitch tension and maximum rate of tension rise were reduced by 55% (p less than 0.05) and 65% (p less than 0.05), respectively. The average force-time integral of the individual crossbridge cycle, calculated by myothermal techniques, was increased by 85% (p less than 0.005) in volume-overload human myocardium. In control and hormonally altered myocardium, both across and within species (control human, control rat, control rabbit, hypothyroid rat, and hyperthyroid rabbit), there was a close relation between the crossbridge force-time integral and the percentage of V3-type myosin isoenzyme in the myocardium. However, hemodynamically altered (volume-overload human and pressure-overload rabbit) myocardium did not follow this relation. Across and within species, there were significant correlations between maximum rate of tension rise and average tension-dependent heat rate (r = 0.97, p less than 0.001) and between maximum rate of tension fall and average tension-independent heat rate (r = 0.82; p less than 0.025). Furthermore, there were close inverse relations between these heat rates and the crossbridge force-time integral. In addition, there was an inverse relation between tension-independent heat and the crossbridge force-time integral. Across and within species total myocardial energy turnover was significantly correlated with the crossbridge force-time integral (relative total heat, r = -0.84, p less than 0.02; relative total-activity related heat, r = -0.88, p less than 0.01). The present findings indicate that 1) factors separate from myosin isoenzymes account for the altered crossbridge cycle in volume-overload human and pressure-overload rabbit myocardium, 2) changes in excitation-contraction coupling processes accompany changes in the crossbridge cycle within and across species, and 3) the force-time integral of the crossbridge cycle is a major determinant of total myocardial energy turnover.