Exposure to thrombus diminishes endothelial derived relaxation in the rabbit carotid artery

Purpose. Thrombus is believed to be deleterious to intimal function. Howeve r, few studies have directly examined this effect. This study examines the effect of thrombus on endothelial-dependent and -independent vasorelaxation in the rabbit carotid artery. Methods. Twelve male New Zealand white rabbits (3.5-4.5 kg) were divided in to two groups of six. Thrombosis was induced in group I by segmental right carotid artery ligation. Group II underwent segmental right carotid ligatio n immediately followed by removal of thrombus with normal saline flush thro ugh an arteriotomy. The left carotid arteries were exposed in both groups a nd served as internal controls. After 4 h, left and right carotid arteries were harvested, sectioned into 6-mm rings, and mounted on isometric force t ransducers in a physiologic bath. Thrombus was removed from the arteries in group I during the ring preparation process. Neither group I nor group II had thrombus in contact with endothelium during ex vivo testing. The arteri al rings were constricted with norepinephrine (1 x 10(-4) M). Endothelium-d ependent and -independent vasorelaxation to acetylcholine (Ach) and s-nitro soacetylpenicillamine, respectively, were measured in a dose-response manne r. Results were expressed as a percentage of vasorelaxation. Statistical analy sis was performed using an analysis of variance. Results. Endothelial-dependent vasorelaxation, which tests for endothelial cell function, was decreased in the thrombus and endothelial ischemia group (I) compared to control as noted by vasorelaxations of 22% vs 34% at 1 x 1 0(-4) molar concentration Ach, and 33% vs 48% at 1 x 10(-3) molar concentra tion Ach, respectively (P = 0.05). By comparison, there was no difference i n the endothelial-dependent vasorelaxation of the endothelial ischemia grou p (II) versus control. Endothelial-independent vasorelaxation, which tests for smooth muscle function, was not affected by either the thrombus and end othelial ischemia group (I) or the endothelial ischemia group (II) compared to the control group. The controls in group I and group II were slightly d ifferent. When this difference was removed, the resulting comparison of tre atments in group I and group II approached significance at molar concentrat ions of 1 x 10(-4), 1 x 10(-5), and 1 x 10(-6) (P = 0.07, 0.06, 0.06). Conclusions. The presence of thrombus within the rabbit carotid artery for a period of 4 h decreases endothelial-dependent relaxation. Four hours of e ndothelial ischemia without thrombus did not change endothelial-dependent v asorelaxation. Neither thrombus nor ischemia alone had any effect on the en dothelium-independent vasorelaxation. We conclude that thrombus is deleteri ous to endothelial function independent of smooth muscle function in the ac ute setting as measured by endothelial-dependent vasorelaxation. (C) 1999 A cademic Press.