Endothelial cell damage and thrombus formation after partial arterial constriction: relevance to the role of coronary artery spasm in the pathogenesis of myocardial infarction.

Abstract

SUMMARY The left anterior descending coronary artery of four dogs and the right common carotid artery of 15 rabbits were subjected to 40-60% reduction in transluminal diameter for 1 hour by partial ligation with suture thread. Scanning electron microscopic examination of the luminal surface of these vessels revealed endothelial craters and balloons, fragmentation and desquamation on the proximal slope of the constriction. Platelet attachment to exposed subendothelial tissues was clearly evident, and microthrombi were seen at the point of maximum constriction. Blood flow, as measured by electromagnetic flow probe, was virtually unchanged upon partial ligation. In control studies, where a second ligature was placed proximal to and before the first to reduce blood flow to the distal constriction site substantially or totally, endothelial desquamation was found in only one of 14 animals, and the number of craters and balloons was significantly reduced. We suggest that endothelial damage and thrombus formation may occur at the site of focal arterial constriction even when the reduction in transluminal diameter is insufficient to alter substantially the rate of flow.THE THREAT posed by coronary vasospasm for the initiation of myocardial ischemia or infarction is assumed to depend on the degree to which the reduction in transluminal diameter results in the interference with coronary blood flow. Further, it is thought that the thrombosis that may accompany vasospasm is a result of the grossly reduced blood flow secondary to a critical vascular constriction and that the interaction of platelets with a damaged vascular wall, with the ensuing release reaction, may further potentiate the coronary spasm." 2 In the present report we present evidence from scanning electron microscopic (SEM) studies that indicates that marked endothelial damage, extensive platelet deposition and thrombus formation may occur at the site of a focal arterial constriction even when the reduction in transluminal diameter is insufficient to alter flow substantially. MethodsFifteen New Zealand white rabbits (3.1 ± 0.4 kg, mean ± SD) were anesthetized with sodium pentobar- The RCCA of five rabbits and the LAD of two dogs were focally constricted 1 cm proximal to the probe by partial ligation with suture thread (0-cotton) to achieve a 50% reduction in transluminal diameter ( fig. 1). The desired degree of luminal constriction was achieved by the apposition of two points on the suture thread; the distance between these points was calculated from the vascular circumference, with the wall thickness (0.1 mm) considered negligible. The diameters were confirmed during SEM examination and varied from 40-60% luminal reduction. Group 2In a second group of five rabbits and two dogs, a second ligature was placed 1 cm proximal and immediately before the first ( fig. 1)

Aneurysm of the rabbit common carotid artery induced by periarterial application of calcium chloride in vivo.

“…These findings support the suggestion that the threat posed by aneurysm is not limited to the consequences of rupture or hemostatic thrombosis. Rather, aneurysm may result in a compromise of parenchymal (organ) perfusion also as a consequence of endothelial damage which is known to occur in areas of irregular luminal contour as a result of hemodynamic injury (1,20,21). Thrombus formation, regardless of the initiating mechanism, may result in partial or total arterial occlusion at the site ofthe aneurysm or result in occlusion ofsmaller vessels distally following platelet shower or embolization from these sites.…”

Cocaine and the Heart

“…18,19 Damaged endothelium at the site of Reviews continued focal arterial constriction may serve as a nidus for platelet adhesion and resultant coronary thrombosis. 20 Cocaine causes the release of norepinephrine from adrenergic nerve terminals which has been shown to cause diffuse coronary vasoconstriction of normal human epicardial coronaries both in vitro and in vivo. 21 Two studies have shown that administration of intranasal cocaine results in a significant reduction of coronary diameter as measured by quantitative coronary angiographic analysis.…”

“…38 However, the current AHA scientific statement on the management of cocaine-associated chest pain and MI recommends avoiding β-blockers in the acute setting. 34 Since cocaine may directly enhance platelet aggregation and potentiate platelet thromboxane production, and since damaged endothelium at a site of focal arterial constriction may serve as a nidus for platelet adhesion, 16,17,20 antithrombotic and antiplatelet agents are also recommended in managing cocaine-associated MIs. 34 In all causes of aortic dissection, blood pressure control to a target systolic pressure of 110 mm Hg may be achieved using morphine sulfate and intravenous β-blockers.…”

Caso 1/ 98 - Instituto do Coração do Hospital das Clínicas - FMUSP

“…No presente caso, encontramos evidências de trombos organizados na microcirculação coronária. Sabe-se que o espasmo coronário pode estar associado a trombose, mesmo em coronárias normais 11 . A cardiopatia isquêmica originou insuficiência cardíaca congestiva e na necropsia foram observados congestão passiva crônica hepática e pulmonar, infartos esplênicos cicatrizados e derrames cavitários.…”