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Acute changes in myosin heavy chain synthesis rate in pressure versus volume overload
T Imamura1, P J McDermott, R L Kent
1Department of Medicine, Medical University of South Carolina, Charleston 29425.
Insights
Pressure overload significantly increases myosin heavy chain synthesis in acute heart conditions, unlike volume overload. This difference in protein synthesis may explain why pressure overload causes more left ventricular hypertrophy than volume overload.
Area of Science:
- Cardiovascular Physiology
- Cardiac Hypertrophy Mechanisms
- Myocardial Protein Synthesis
Background:
- Left ventricular hypertrophy (LVH) differs between pressure overload (e.g., aortic stenosis) and volume overload (e.g., mitral regurgitation).
- The discrepancy in LVH severity is potentially linked to myocardial protein synthesis and degradation rates.
Purpose of the Study:
- To investigate early changes in myosin heavy chain synthesis rate.
- To compare responses to severe acute pressure overload versus severe acute volume overload.
Main Methods:
- Utilized canine models for acute pressure overload (aortic balloon inflation) and volume overload (mitral chordal rupture).
- Measured hemodynamic parameters: pressure gradient (119.8 mmHg) and regurgitant fraction (0.67).
- Quantified myosin heavy chain synthesis rate in control, pressure overload, and volume overload groups.
Main Results:
- Myosin heavy chain synthesis rate in controls was 2.7%/day.
- Volume overload showed a similar synthesis rate to controls (2.7%/day).
- Pressure overload significantly increased synthesis rate by 30% to 3.5%/day (P < .05).
Conclusions:
- Acute pressure overload markedly elevates myosin heavy chain synthesis compared to acute volume overload.
- Differential regulation of protein synthesis may contribute to the distinct degrees of hypertrophy observed in pressure vs. volume overload cardiac lesions.
Abstract:
The left ventricular hypertrophy that develops with the volume overload of mitral regurgitation is relatively less than that which develops with the pressure overload of aortic stenosis even when both lesions are severe. The hypertrophy that develops must be the sum of changes in the rate of myocardial protein synthesis and degradation. In the present canine study, we explored early changes in the synthesis rate of myosin heavy chain in response to severe acute pressure overload versus that of the severe acute volume overload of mitral regurgitation. We tested the hypothesis that in acute overload, the rate of protein synthesis would increase less in the volume-overload model than in the pressure-overload model, a potential partial mechanism for the discrepancy in the eventual total amount of hypertrophy that develops in these two lesions. Acute pressure overload was produced by inflating a balloon in the descending aorta, and acute volume overload was produced by using our closed-chest mitral chordal rupture technique. In both models, the hemodynamic lesion that was created was severe. In eight dogs with pressure overload, the average gradient across the balloon was 119.8 +/- 6.1 mm Hg. In six dogs with volume overload, the average regurgitant fraction was 0.67 +/- 0.06. Six other dogs served as controls. The average rate of myosin heavy chain synthesis in control dogs was 2.7 +/- 0.2% per day, virtually identical to the rate we found in the severe volume-overload model. In contrast, the rate was increased in the pressure-overload model by 30% to 3.5 +/- 0.3% per day (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)