CELLULAR MECHANISMS OF MYOCARDIAL INFARCT EXPANSION

Infarct expansion is acute regional dilatation and thinning of the infarct zone. There are several possibilities for the mechanism of this alteration in cardiac shape: thinning could be caused by 1) cell rupture, 2) a reduction in the intercellular space, or 3) stretching of myocytes or 4) slippage of groups of myocytes so that cells are distributed across the wall. To determine the relative contribution of these cellular mechanisms of wall thinning and dilatation, detailed study of transverse histological sections of rat hearts with infarct expansion was performed 1, 2, and 3 days after coronary ligation. The number of cells across the wall was determined in six regions within, adjacent to, and remote from the infarct. Cell counting was performed so that the total number of cells across the wall and the number of cells per unit length (cell density) across the wall were determined. The transmural cell count and the cell density were correlated with the wall thickness in each region. Myocyte cross-sectional areas and sarcomere lengths were also measured. The results from the infarct expansion hearts were compared with those of sham-operated control hearts that had been similarly analyzed. To ensure that mechanisms identified in the rat were applicable to human infarct expansion, five hearts from disease were studied histologically in a similar fashion. Wall thinning occurred in all regions of the rat infarct expansion hearts compared with controls (p < 0.001) but, as expected, was most pronounced in the infarct zone. A decrease in the number of cells across the wall accompanied the wall thinning at each site (p < 0.0001), and this change in cell number was highly correlated with the changes in wall thickness (r = 0.915, p < 0.001). Cell density increased from contorls only within the infarct zone (p < 0.001) and accounted for at most 20%of the thinning in that region. The change in cell density was attributable to both cell stretch (measured by increased sarcomere length and decreased myocyte cross-sectional area) and a decrease in the intercellular space. A similar strong correlation between wall thinning and decreased number of cells across the wall was identified in the human hearts (r = 0.94, p < 0.001). Thus, a decrase in the number of cells across the wall accounts for most wall thinning in the infarct zone and all thinning in noninfarcted regions. In nonfarcted regions, cell slippage accounts for all thinning. Cell stertch and loss of intercellular space are confined to the infarct zone and contribute less to wall thinning than does cell slippage.