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DOI: 10.1055/s-0032-1332459
The coronary microcirculation in hamster-to-rat cardiac xenografts
Objectives: The aim of this study was to establish a new experimental model to directly study the coronary microcirculation during early ischemia/reperfusion (I/R) injury in rodent cardiac xenografts.
Methods: Intravital fluorescence microscopy (IVM) of the subepicardial microcirculation in heterotopically transplanted hamster-to-rat cardiac xenografts was performed at 30 and 90 min of reperfusion. Microcirculatory perfusion characteristics as well as interactions of leukocytes and thrombocytes with the endothelium of postcapillary coronary venules were assessed.
Results: IVM allowed detailed imaging of the subepicardial coronary microcirculation in cardiac hamster-to-rat xenografts. Postcapillary venular blood flow was 0.41 ± 0.02 mm/s and 0.46 ± 0.01 mm/s at 30 and 90 min of reperfusion. The microvascular leakage was 128 ± 3% and 132 ± 4%. We also found tremendous numbers of rolling and firmly adhering leukocytes in postcapillary venules, equally at both time points. Interestingly, thrombocyte endothelial cell interactions decreased during reperfusion, i.e. there were 294 ± 97 and 110 ± 50 cells/min/mm2 rolling and 234 ± 39 and 194 ± 41 cells/mm2 firmly adhering thrombocytes in coronary venules. Validating the xenogeneic approach, we found markedly reduced xenograft survival times of 3.2 ± 0.2 days. Histology revealed mild rejection scores at 90 min of reperfusion, but severe myocardial damage in rejected xenografts with predemonately diffuse intramyocardial bleeding.
Conclusion: We established and validated a novel experimental approach to study xenograft rejection in vivo. IVM is a proper means to study coronary microcirculatory dysfunction in reperfused rodent xenografts.