Compromised microvascular integrity in ischemic myocardium
West, P.N.; Connors, J.P.; Clark, R.E.; Weldon, C.S.; Ramsey, D.L.; Roberts, R.; Sobel, B.E.; Williamson, J.R.
Laboratory Investigation; a Journal of Technical Methods and Pathology 38(6): 677-684
1978
ISSN/ISBN: 0023-6837 PMID: 661224 Document Number: 125656
The time-dependent effects of ischemia on the structural and functional integrity of the coronary vasculature were evaluated in open chest anesthetized dogs. Occlusion of the left anterior descending coronary artery was produced in 49 animals for selected intervals from 30 min to 6 h. Dogs were then sacrificed after i.v. injection of 100 mg/kg of colloidal C. Hearts were sectioned and mural deposition of C in vessels (vascular labeling), indicative of compromised endothelial integrity and pathologically increased permeability, was evaluated by light microscopy and EM. C deposition was most conspicuous in capillaries and venules up to 150 .mu.m in diameter and was demonstrable after only approximately 15 s of exposure to circulating C. The extent of mural deposition was proportional to the duration of ischemia; after 4, or more, h of occlusion, labeled vessels were demonstrable in all hearts. Ultrastructural changes, including degeneration and fragmentation of endothelial cells and packing of C particles against basement membrane denuded of endothelium, were observed in capillaries as well as in venules. At the later intervals of ischemia, i.e., 4 to 6 h, mural deposition of C as well as intramural hemorrhage were also observed in arterioles up to 150 .mu.m in diameter; no changes were evident in larger arteries or veins. Functional as well as structural integrity of the microvasculature apparently is markedly compromised relatively early (within 4 h) after coronary occlusion.