Acute Changes in Myosin Heavy Chain Synthesis Rate in Pressure Versus Volume Overload

• Published in: Circulation research 1994-09, Vol.75 (3), p.418-425
• Main Authors: Imamura, Takuroh, McDermott, Paul J, Kent, Robert L, Nagatsu, Masayoshi, IV, George Cooper, Carabello, Blase A
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Blood Pressure; Dogs; Heart Rate; Hypertrophy, Left Ventricular - metabolism; Hypertrophy, Left Ventricular - physiopathology; Kinetics; Leucine - metabolism; Mitral Valve Insufficiency - metabolism; Mitral Valve Insufficiency - physiopathology; Myocardium - metabolism; Myosins - biosynthesis; Radioisotope Dilution Technique; Reference Values; RNA, Transfer, Leu - biosynthesis; Stroke Volume; Tritium
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.75.3.418

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