Cerebral blood flow regulation following hypoxic attacks and seizures in the newborn piglet

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Abstract in foreign language

Asphyxia affects approximately 5-10 % of the newborn infants and may have life-long adverse consequences, such as mental retardation and epileptiform seizures. Both hypoxic attacks, including asphyxia and cerebral ischemia, and seizures disrupt the coupling between cerebral metabolic needs and blood supply thereby lead to neuronal damage and impaired cerebrovascular reactivity and function. Although hypoxia is reversed the fastest by ventilation with 100% oxygen (O2) upon resuscitation, hyperoxygenation may cause additional damage. We tested if reventilation with room air (RA, 21% O2) or 100% O2 after asphyxia would differentially affect haemodynamic events and neuronal damage in different brain areas of newborn pigs. We found O2 toxicity after asphyxia in the hippocampus and cerebellum, but not in the cerebral cortex or basal ganglia. The observed regional differences may be associated with local haemodynamic factors, since reactive hyperemia was significantly higher in the cerebellum than in the cerebral cortex. Carbon dioxide (CO2) is a powerful dilator of the cerebral vessels by a mechanism involving cyclooxygenase (COX) metabolites in the newborn. This responsiveness to CO2/hypercapnia is sensitive to hypoxia/ischemia and is used as a measure of the cerebrovascular function. Acetazolamide (AZD), a carbonic anhydrase inhibitor, produces cerebral vasodilation presumably due to CO2 retention and acidosis. We examined if cerebrovascular effects of AZD were similar to hypercapnia in the newborn pig. The mechanism of AZD-induced cerebral vasodilation appears to be similar/identical to hypercapnia, since both reactions were abolished by the non-selective COX-inhibitor indomethacin, unaltered by ibuprofen and L-NAME and were significantly attenuated after ischemia/reperfusion. Cerebrovascular function is protected against seizure-induced damage by enhanced endogenous carbon monoxide (CO) production by heme oxygenase. We hypothesized that exogenous CO derived from the CO releasing molecule-A1 (CORM-A1) exerts protective effects on the cerebral microvasculature. Seizures reduced postictal cerebrovascular responsiveness to physiologically relevant vasodilators (bradykinin, hemin, and isoproterenol), which was prevented by CORM-A1-pretreatment. We provided novel data on the cerebrovascular regulation in the hypoxic and epileptic newborn.

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