Changes in cerebral vascular reactivity occur early during cardiopulmonary bypass in the rat.
BACKGROUND: Cardiopulmonary bypass (CPB) is known to cause cerebrovascular dysfunction. The etiology of these complications is complex, but disruption of normal cerebral endothelial function as a consequence of inflammatory or hypoperfusion phenomena have been implicated. The aim of this study was to investigate the effect of CPB time on cerebrovascular reactivity and to investigate the correlation of these findings with measured inflammatory markers. METHODS: Cardiopulmonary bypass was carried out for 30 or 60 minutes on two groups of rats. Sham groups underwent the same surgical procedure without CPB. The middle cerebral artery was harvested and prepared for assessment of induced endothelial and vascular smooth muscle cell responses. Systemic inflammation was evaluated by measuring tumor necrosis factor-alpha and immunohistochemical staining for intercellular adhesion molecule-1. RESULTS: Acetylcholine caused a dose-dependent vasodilation in the control groups that was absent in animals undergoing CPB (21.3% +/- 1.3% increase in diameter at 30 minutes in the sham group compared with 5.4% +/- 1.1% in the corresponding CPB group, p < 0.001). Significantly, this was apparent after only 30 minutes of CPB. Cardiopulmonary bypass did not alter the response to sodium nitroprusside (45.3% +/- 8.6% after 30 minutes in the sham group compared with 57.8% +/- 8.0% in the corresponding CPB group, p < 0.2). Furthermore, the contractile response to serotonin remained intact in all groups (32.9 +/- 4.6 and 27.6 +/- 2.6 at 30 and 60 minutes, respectively, in the sham groups compared with 23.1 +/- 1.6 and 28.0 +/- 4.4 in the corresponding CPB groups, p < 0.2). Cardiopulmonary bypass also led to an early and marked increase in tumor necrosis factor-alpha and overexpression of intercellular adhesion molecule-1. CONCLUSIONS: Cerebrovascular impairment appears early after the onset of CPB. The specific loss of acetylcholine-induced vasodilation suggests endothelial cell dysfunction rather than impaired vascular smooth muscle response to nitric oxide. This loss of endothelium-dependent regulatory factors after CPB may enhance vasoconstriction, impair cerebrovascular function, and contribute to neurologic injury after CPB.