Abstract 357: Cerebral Arterial Endothelial Dysfunction in the Post-Cardiac Arrest Period

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Introduction: Cardiac arrest (CA) has a poor prognosis due to brain injury that progresses over time. Endothelial dysfunction may play an important role in the impairment of the cerebral circulation after CA. Aims: To investigate 1) whether endothelial dysfunction is present in cerebral arteries, and 2) if the altered endothelial function is caused by increased activity of calcium-activated potassium (K ca ) channels. Methods: Male Sprague-Dawley rats (403g±24g) were anaesthetized, intubated and ventilated. Four groups were examined; two CA groups observed for either 2 hours (2h-CA, n=10) or 4 hours (4h-CA, n=10) and two corresponding sham groups (2h-sham, n=10; 4h-sham, n=10). Following 7 minutes of asphyxial CA, the rats were resuscitated using adrenaline, ventilation, and chest compressions. Middle cerebral arteries were isolated and examined in wire-myographs. Results: Cerebral vasodilation was significantly enhanced in response to bradykinin in arteries from 4h-CA rats when compared to 4h-sham rats (4h-sham: E max 58% (5.57 of 9.69) ± 6% vs 4h-CA: E max 84% (6.16 of 7.32) ± 4%, p=0.007). Likewise, vasodilation induced by NS309 (K Ca -channel activator) was increased in CA rats when compared to sham rats. In the presence of L-NAME (NO synthase inhibitor), bradykinin induced vasodilation was significantly augmented in 4h-CA rats when compared to 4h-sham rats, whereas SNP (NO donor) induced vasodilation was similar between groups. In the presence of L-NAME and K Ca -channel blockers (UCL1684 and ICA-17043), bradykinin induced vasodilation was abolished in cerebral arteries in all four groups. Conclusion: Our findings demonstrate an enhanced endothelial-dependent vasodilation in cerebral arteries in the post-cardiac arrest period. The increased vasodilatory response may be explained by increased endothelial K Ca -channel activity and bioavailability of NO, and may contribute to dysregulation of cerebral blood flow after CA.