The "no-reflow" phenomenon, the occurrence of areas with very low flow in hearts reperfused after ischemia, is thought to be largely established at the time of reperfusion as a result of microvascular damage induced by ischemia. In the present study we sought to determine whether additional impairment of tissue perfusion might also occur during the course of reperfusion. Open-chest dogs were subjected to 90 minutes of left circumflex coronary artery occlusion and reperfused for 2 minutes (n=7) or 3.5 hours (n=8). Myocardial perfusion was visualized in left ventricular slices following in vivo injection of the fluorescent dye thioflavin-S just before killing. The area of impaired perfusion (absent thioflavin) averaged 9.5+3.0% of the risk region in dogs reperfused for 2 minutes, whereas it was nearly three times as large in dogs reperfused for 3.5 hours (25.9 ±8.2% of the risk region, p<0.05). Serial measurements of flow by microspheres during reperfusion demonstrated zones within the postischemic myocardium that were hyperemic 2 minutes after reperfusion, with adequate flow still present at 30 minutes, but with a subsequent marked fall in perfusion. After 3.5 hours these areas showed negligible flow (0.13 ±0.03 ml/min/g) and no thioflavin uptake. Tissue samples showving postischemic impairment in perfusion had received virtually no collateral flow during ischemia (<0.01 mlUmin/g), whereas collateral flow was significantly higher in adjacent thioflavin-positive zones (0.04±0.01 ml/min/g in endocardial samples and 0.07±0.02 ml/min/g in samples from the midmyocardium, p<0.001 vs. thioflavin-negative areas). Areas that showed late impairment of flow invariably demonstrated contraction band necrosis, which contrasted with the pattern of coagulation necrosis observed in areas of "true" (i.e., immediate) no-reflow. Intracapillary erythrocyte stasis and marked intravascular neutrophil accumulation (to levels >20-fold that found after 2 minutes reperfusion) were typically observed in areas of delayed impairment to flow. Obstruction to flow at the capillary level was confirmed in additional dogs in which the heart was injected postmortem with silicone rubber to delineate the microvascular filling pattern. Areas of absent capillary filling were much more extensive after 3.5 hours than after 2 minutes reperfusion. Thus, this study shows that the occurrence of areas of markedly impaired perfusion in postischemic myocardium is related only in part to an inability to reperfuse certain areas on reflow. A more important factor is represented by a delayed, progressive fall in flow to areas that initially received adequate reperfusion. This phenomenon develops in regions receiving no collateral flow during ischemia and is associated with neutrophil accumulation and capillary plugging late during the course of reperfusion. (Circulation

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 less cells are distributed across the wall. To determine the relative contributions 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 patients who died within 3 days of infarction and two hearts from patients without coronary disease were studied histologically in a similar fashion. Wall thinning occurred in all regions of the rat infarct expansion hearts compared with controls (p <0.0001) 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 controls 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 decrease in the number of cells across the wall accounts for most wall thinning in the infarct zone and all thinning in noninfarcted regions. In noninfarcted regions, cell slippage accounts for all thinning. Cell stretch and loss of intercellular space are confined to the infarct zone and contribute less to wall thinning than does cell slippage. (Circulation 1988;78:186-201) I nfarct expansion describes the disproportionate thinning and dilatation of acutely infarcted myocardium that occurs within the first 24 hours after infarction1 2 and leads to early cardiac dilatation.34 These early structural changes within the infarct zone are accompanied by similar but less pronounced changes in wall thickness and ...

Infarct expansion, regional dilation and thinning of the infarct zone, occurs within 1 day after myocardial infarction. Whether the early change in regional shape of infarct expansion affects the architecture of remote normal regions is unknown. To study this question, 45 rats with a transmural infarct were killed at 1, 2 and 3 days after infarction and their hearts were examined for infarct size and extent of expansion. Wall thickness and radius of curvature were measured within, adjacent to and remote from the infarct zone. Equivalent regions were analyzed in eight control hearts. The extent of disproportionate wall thinning and increased radius of curvature within the infarct zone of hearts with expansion was not dependent on infarct size. Significant wall thinning and increased regional radius of curvature were also seen in adjacent and remote regions of the hearts with expansion (p less than 0.001). These structural changes outside of the infarct occurred independent of infarct age and size, and were not seen in hearts without infarct expansion. Thus, when disproportionate thinning and dilation occur in the infarct region, they are accompanied by a distortion in shape of the entire heart including remote normal myocardium. This remote remodeling of noninfarcted myocardium correlates with extent of expansion, but not with age or size of the infarct.

(4), a second possibility is that steroids lead to a prolonged phase during which "soft" necrotic myocardium thins and dilates. The third possibility is that steroids act solely by promoting the early expansion of freshly necrotic myocardium before collagen deposition begins. Infarct expansion, the thinning and dilatation of freshly infarcted myocardium that begins within the first few hours after transmural infarction,