MYOFIBRILLAR ADAPTATIONS DURING CARDIAC-HYPERTROPHY

The main purpose of this study was to determine the transmural adaptiv e changes that occur in cell size, myofibrils, and myosin isoforms fro m the endocardium (ENDO) to the epicardium (EPI) of the left ventricle (LV) of the rat heart during compensatory hypertrophy. Hypertrophy wa s induced by supra-renal aortic constriction for periods of 2, 7, 15 a nd 30 days. Percent left ventricular hypertrophy averaged 63 +/- 9.7% at 30 days following constriction. A significant (p < 0.05) transmural gradient in the V-3 myosin isoform (9 +/- 0.7% ENDO vs. 5 +/- 1.8% EP I) was initially observed at 7 days and was still evident by 30 days ( 25 +/- 3.6% ENDO vs 15 +/- 2.0% EPI). Cell cross-sectional area was al so greater (p < 0.05) in the ENDO than in the EPI at 7,15 and 30 days. MF diameter was determined only at 30 days and was found to be simila r to control values in both the hypertrophied ENDO (sham 1.24 +/- 0.05 vs hyp 1.18 +/- 0.09 mu m) and EPI (sham 1.17 +/- 0.08 vs hyp 1.06 +/ - 0.08 mu m). The combined effects of cardiac myocyte hypertrophy with no change in MF diameter resulted in a calculated increase of approxi mately 70% in the number of myofibrils per myocyte both in the ENDO an d EPI. It was concluded that the adaptive strategy of the left ventric ular free wall to pressure overload was to initially increase myocyte cross-sectional area and then switch myosin expression from V-1 to V-3 , both of which proceeds transmurally from the sub-endocardium towards the sub-epicardium. Along with these transmural adaptations, myofibri ls increased in number while maintaining myofibrillar diameter with th e apparent intent of conserving diffusion distance for calcium from th e sarcoplasmic reticulum to the innermost contractile filaments of the myofibrils.