Effects of reperfusion after coronary artery occlusion on post-infarction scar tissue

Abstract

Early reperfusion after a coronary occlusion may reduce myocardial infarct size, but late reperfusion into necrotic myocardium may alter post-infarction healing. In rabbits, we compared 1- or 3-week-old scars resulting from permanent coronary occlusion to those resulting from a 1- to 3-hour occlusion followed by reperfusion. Reperfusion at 1 hour post-occlusion did not affect scar mechanical properties assessed a 1 week post-infarction, but at 3 weeks post-infarction, these scars had a tensile strength significantly lower than those not reperfused (78 ± 11 vs 158 ± 15 g/mm2, P < 0.001). They also were composed of a mixture of fibrous tissue (58 ± 8%) and myocytes (43 ± 8%) with hydroxyproline content of 23 ± 2.5 mg/g drug weight. The nonreperfused scars had a higher proportion of fibrous tissue (73 ± 3%) by histological evaluation and a 35% higher hydroxyproline content (31 ± 2 mg/g dry weight, P < 0.001) than the scar reperfused after 1 hour. In contrast, 3-week-old scars resulting from 'late' reperfusion at 3 hours post-occlusion were similar to nonreperfused scars in fibrous tissue composition and hydroxyproline content. Nonetheless, the tensile strength of these scars reperfused 3 hours post-occlusion was significantly less than that of the nonreperfused scars (72 ± 5 vs 158 ± 15 g/mm2, P < 0.001). The lower tensile strength was associated with a lower collagen cross-link density in this reperfused group of scars. At physiological stress levels (approximately 3 g/mm2), all groups of reperfused and nonreperfused scars had similar mechanical properties in term of natural strain, stiffness, creep, and stress relaxation. Thus, although the reperfused scars ruptured more easily at high stresses, when assessed at physiological stresses their mechanical properties were not significantly different from those of nonreperfused scars.