REGIONAL MYOCYTE HYPERTROPHY PARALLELS REGIONAL MYOCARDIAL DYSFUNCTION DURING POST-INFARCT REMODELING

After large myocardial infarction (MI), left-ventricular (LV) remodeli ng is characterized by cavity dilatation, eccentric hypertrophy, and r egional mechanical dysfunction. We wished to correlate cellular hypert rophy chronically after MI with in vivo function on a regional basis w ithin non-infarcted myocardium. Twelve sheep were studied. Seven under went coronary ligation to create an anteroapical MI, Magnetic resonanc e imaging (MRI) was performed once in controls, and prior to and 8 wee ks after infarction, for measurement of LV mass, volumes. ejection fra ction, and regional intramyocardial circumferential shortening (%S), M yocyte morphometric indices (cell volume, length, cross-sectional area , width, and length/width ratios) were measured from myocytes isolated from regions adjacent to (within 2 cm of the infarct border) and remo te from the infarct and at corresponding loci in the control animals. From baseline to 8 weeks after infarction in the infarcted animals, en d-diastolic volume increased from (mean +/- S.D.) 1.9 +/- 0.4 ml/kg to 2.6 +/- 0.4 ml/kg (P<0.02) and EF fell from 49 +/- 6 to 35 +/- 6% (P< 0.02). LV mass trended upwards from 2.2 +/- 0.4 to 2.6 +/- 0.4 g/kg (P = N.S.). Regionally, %S in the region adjacent to the infarct fell (f rom 19 +/- 3 to 13 +/- 3%, P<0.003) while remote %S did not change. Ce ll volume in adjacent non-infarcted regions was greater than that in r emote non-infarcted regions (3.8 +/- 0.9 x 10(4) mu m(3) nu 2.6 +/- 0. 8 x 10(4) mu m(3), P<0.006) and this difference (+1.2 +/- 0.7 x 10(4) mu m(3)) was greater than the corresponding regional difference in con trols (+0.4 +/- 0.2 x 10(4) mu m(3), P<0.05), Similarly, myocytes in a djacent non-infarcted regions were longer (138.0 +/- 10.1 mu m) than i n remote regions (123.7 +/- 10.1 mu m, P<0.002), and this difference ( +14.3 +/- 7.2 mu m) was greater than that in controls (-1.4 +/- 5.6 mu m, P<0.003). Adjacent %S correlated inversely with adjacent myocyte c ell volume (r = -0.72, P<0.009) and cell length (r = -0.70, P<0.02). I n mechanically dysfunctional non-infarcted regions adjacent to chronic transmural myocardial infarction in the remodeled LV, disproportionat e cellular hypertrophy occurs, predominantly due to an increase in cel l length. Mechanical dysfunction in these regions correlates with cell lengthening and hypertrophy, (C) 1998 Academic Press