Endothelial activation through brain death?

Background: Brain death induces myocardial dysfunction and multifocal microscopic myocardial necrosis in dogs; however, the pathogenetic pathways between brain death and cardiac damage remain incompletely understood. We hypothesized that brain death might induce a propensity toward coronary vasospasms, possibly by endothelial dysfunction. We therefore studied the effect of serotonin and acetylcholine on tension generated by isolated coronary artery segments from control and brain dead dogs Methods: Coronary segments were isolated I hour after brain death that was induced by the inflation (15 ml saline) of an extradurally placed balloon or from sham-operated time-matched controls. Studied were the effect of serotonin on isometric tension, with and without pre-constriction with prostaglandin F-2alpha (PGF(2alpha)), and the effect of acetylcholine after pre-constriction. Results: Coronary segments from brain dead dogs exhibited severe vasoconstriction when serotonin (10(-7), 10(-6), and 10(-5) mol/liter) was administered, a reaction that was barely detectable in control segments. After pre-construction with PGF(2alpha), serotonin caused only significant vasodilation in a concentration of 10(-5) mol/liter, unlike in control segments where 10(-6) mol/liter had already induced a highly significant vasodilation. The reaction on acetylcholine was identical in both groups. Conclusion: Brain death induces changes in coronary vasoreactivity in dogs, with a highly increased sensitivity for the vasospastic effects of serotonin. It is, however, not merely caused by aspecific endothelial dysfunction, as evidenced by the normal reaction on acetylcholine. These alterations in coronary artery properties might contribute to the myocardial damage seen after brain death.