STRUCTURAL BASIS FOR CHANGES IN LEFT-VENTRICULAR FUNCTION AND GEOMETRY BECAUSE OF CHRONIC MITRAL REGURGITATION AND AFTER CORRECTION OF VOLUME OVERLOAD

Left ventricular function and myocyte structure were examined in three groups of dogs: (1) 3 months of mitral regurgitation caused by chorda l rupture (n = 7); (2) chronic mitral regurgitation followed by mitral valve replacement and a 3-month recovery period (n = 7), and (3) sham controls (n = 8). The left ventricular end-systolic stiffness constan t (K(ess)) was measured as an index of left ventricular contractile fu nction with stress-strain relationships obtained by cinecatheterizatio n. Isolated myocyte structure and composition were examined with compu ter-assisted morphometry and nuclear area computed with deoxyribonucle ic acid fluorescence. Left ventricular contractile function was signif icantly depressed with chronic mitral regurgitation compared with cont rol values (K(ess), 2.1 +/- 0.1 versus 3.6 +/- 0.2; p < 0.05) and retu rned to control values with mitral valve replacement (3.8 +/- 0.2). Le ft ventricular mass significantly increased in both the mitral regurgi tation and mitral valve replacement groups compared with control value s (121 +/- 10, 120 +/- 5 versus 95 +/- 9 gm, respectively; p < 0.05). Myocyte length increased with mitral regurgitation beyond control valu es (194 +/- 4 versus 218 +/- 8 mum; p < 0.05) and increased beyond mit ral regurgitation values after mitral valve replacement (231 +/- 7 mum ; p < 0.05). Myocyte volume with mitral regurgitation increased slight ly beyond control values (33.5 +/- 0.7 versus 37.6 +/- 1.3 mum3; p = 0 .15) and significantly increased with mitral valve replacement (40.1 /- 1.2 mum3; p < 0.05). Myocyte myofibril volume significantly decline d with mitral regurgitation compared with control values (14.8 +/- 1.5 versus 22.2 +/- 0.7 mum3; p < 0.05) and significantly increased beyon d both mitral regurgitation and control values with mitral valve repla cement (27.1 +/- 1.1 muM3; p < 0.05). Myocyte nuclear area with mitral regurgitation remained unchanged from control values (1430 +/- 122 ve rsus 1163 +/- 89 mum2) but increased significantly with mitral valve r eplacement (2209 +/- 250 mum2; p < 0.05). In summary, the left ventric ular contractile dysfunction with chronic mitral regurgitation is acco mpanied by increased myocyte length and reduced myofibril content. In contrast, the left ventricular hypertrophy and improved left ventricul ar pump function with mitral valve replacement were due to increased m yocyte volume and increased contractile protein content.