Cerebrovascular response to continuous cold perfusion and hypothermic circulatory arrest

Clinical and laboratory studies have documented changes in cerebrovascular resistance after hypothermic circulatory arrest, both with and without adjunctive cerebral perfusion modalities. This study was designed to clarify whether these changes are due to cerebral edema, resistance vessel abnormalities, or alterations in the cerebral microcirculation.

Four mature swine underwent hypothermic circulatory arrest for 60 minutes, and 7 mature swine underwent cold cerebral perfusion for 60 minutes to simulate antegrade selective perfusion. All were rewarmed and weaned from cardiopulmonary bypass. Pial vascular diameter and reactivity were measured in vivo through a cranial window and ex vivo in an organ chamber; cerebral microvascular endothelium was studied in culture for release of vasoactive mediators. Cerebral water content was recorded.

Cold perfusion caused pial arteriole and venule constriction, whereas hypothermic circulatory arrest alone caused pial arteriole and venule dilatation. Cold perfusion caused a temporal loss of endothelium-dependent vasodilatation, most notably to bradykinin. Hypothermic circulatory arrest caused a loss of nitric oxide-mediated endothelium-dependent vasodilatation. Endothelium-independent vasoreactivity remained intact in both groups. Endothelial cells from the cold group had a vasoconstrictive secretory phenotype, whereas endothelial cells from the hypothermic circulatory arrest group had a vasodilatory phenotype. Cerebral water content was the same in both groups.

The increase in cerebrovascular resistance observed after cold cerebral perfusion is caused by resistance vessel constriction and may be promoted by an altered microcirculation. Hypothermic circulatory arrest alone is associated with endothelium-dependent vasoparesis. Both could contribute to cerebral injury in the early hours after operation.