Myocardial infarct extension during reperfusion after coronary artery occlusion: Pathologic evidence

AbstractObjectives. The goal of this study was to demonstrate myocardial infarct extension during reperfusion within the same animal.Background. Whether myocardial reperfusion can result in the extension of myocardial necrosis remains controversial. The transformation of reversibly injured myocytes into irreversibly damaged cells after reperfusion has been difficult to demonstrate pathologically.Methods. New Zealand White rabbits (Group I, n = 10) were subjected to 30 min of coronary artery occlusion and 180 min of reperfusion. Horseradish peroxidase, a tracer protein that permeates the sarcolemma of irreversibly injured myocytes, was used to quantitate myocyte necrosis at the beginning of reperfusion. Within the same heart, infarct size was measured after 180 min of reperfusion by triphenyttetrazolium chloride (TTC) staining. In separate experiments to demonstrate the validity of the model, rabbits were subjected to 30 min of coronary occlusion, followed by intravenous infusion of horseradish peroxidase and rapid induction of death (Group II) or 30 min of occlusion, 180 min of reperfusion with horseradish peroxidase administered after 180 min of reperfusion and TTC staining after induced death (Group III).Results. In Group I, infarct size at the onset of reperfusion, delineated by horseradish peroxidase, measured 45.3 ± 2.8% of the area of risk and was significantly less than TTC-delineated infarct size after 189 min of re perfusion (59.8 ± 33%, p = 0.0002). By electron microscopy, border areas within the ischemic bed demonstrated irreversibly injured horseradish peroxidasepositive myocytes adjacent to irreversibly injured horseradish peroxidase-negative myocytes, suggesting that farther cell death occurred during reperfusion. In Group II, infarcts delineated by horseradish peroxidase after 30 min of coronary occlusion were similar in size to infarcts measured by this tracer in Group I. In Group III, infarcts delineated by horseradish peroxidase at 180 min of reperfusion were similar in size to infarcts measured by TTC and similar to TTC-delineated infarcts measured at 180 min of reperfusion in Group I.Conclusions. These results provide evidence that there is a subset of myocytes in border areas within the ischemic region that are viable at the beginning of reperfusion but subsequently progress to irreversible injury during the reperfusion period

Coronary Responses and Differential Mechanisms of Late Stent Thrombosis Attributed to First-Generation Sirolimus- and Paclitaxel-Eluting Stents

ObjectivesThe purpose of this study was to assess the mechanism(s) of late stent thrombosis (LST) and vascular healing responses in first-generation polymeric drug-eluting stents (DES).BackgroundRecent clinical trials have reported variations in late lumen loss between first-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Little is known, however, about the vascular responses, time course of healing, and underlying mechanism(s) of complications of LST between platforms in human coronary implants.MethodsThe overall analysis included 174 cases (230 DES lesions) from the CVPath Institute's stent registry. Histomorphometry was performed on coronary stents from 127 patients (171 lesions) who died ≥30 days after receiving stent implants in which fibrin deposition, endothelial strut coverage, inflammatory response, and mechanism(s) of in-stent thrombosis were assessed.ResultsBoth platforms demonstrated increased neointimal thickness over time where values were greater in PES (mean 0.13 mm; range 0.03 to 0.20 mm) than SES (mean 0.10 mm; range 0.04 to 0.15 mm; p = 0.04). The percentage of uncovered struts was similar between SES and PES including stents with LST (SES = 21% vs. PES = 27%; p = 0.47). The underlying mechanism(s) of LST, however, was strikingly different between platforms; localized strut hypersensitivity was exclusive to SES, whereas malapposition secondary to excessive fibrin deposition was the underlying cause in PES. Moreover, although both PES and SES showed nearly complete strut coverage after 12 months for on-label use, the majority of stents placed for off-label indications remained unhealed after 12 months in both types of DES.ConclusionsDifferential mechanisms of LST involving either hypersensitivity or excessive fibrin were identified between first-generation DES in which overall stent healing was further delayed in DES placed for off-label indications