Endothelial Dysfunction in Cerebral Microcirculation During Hypothermic Cardiopulmonary Bypass in Newborn Lambs † 1908

Inflammatory stimuli and/or mechanical stresses associated with hypothermic cardiopulmonary bypass (HCPB) could potentially impair cerebrovascular function resulting in inadequate cerebral perfusion. We hypothesize that HCPB is associated with endothelial and/or vascular smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore, we studied the cerebrovascular response to endothelium-dependent vasodilator, acetylcholine (ACh), endothelium-independent nitric oxide donor, sodium nitroprusside (SNP), and vasoactive amine, serotonin, in newborn lambs undergoing HCPB (nasopharygeal temperature = 18°C). Studies were performed on thirteen newborn lambs equipped with a closed cranial window allowing for direct visualization of surface pial arterioles. Six animals were studied while undergoing HCPB while seven served as nonbypass, warm (37°C) controls. Pial arteriolar caliber(range = 111 to 316 μm diameter) was monitored using video microscopy. Topical application of ACh caused dose-dependent increase in arteriolar diameter in the control group (18±6%; 163±22 μm to 190±18 μm) that was absent in animals undergoing HCPB. HCPB did not alter the vasodilation in response to SNP (19±7%; 173±26 μm to 202±21 μm). Furthermore, the contractile response to serotonin(26±4%; 172±14 μm to 124±9 μm) was fully expressed during HCPB. The specific loss of ACh-induced vasodilation suggests endothelial cell dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. It is speculated that loss of endothelium-dependent regulatory factors in the cerebral microcirculation during HCPB may enhance vasoconstriction and impaired cerebrovascular function may be a basis for associated neurological injury during or following HCPB.

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Supported by a grant from Allegheny Singer Research Institute

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Wagerle, L., Russo, P., Dahdah, N. et al. Endothelial Dysfunction in Cerebral Microcirculation During Hypothermic Cardiopulmonary Bypass in Newborn Lambs † 1908. Pediatr Res 43, 325 (1998). https://doi.org/10.1203/00006450-199804001-01931

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