DIFFERENTIAL CONTRACTILE RESPONSE OF MIDDLE CEREBRAL ARTERY(MCA) TO HYPOTHERMIA DURING PERINATAL DEVELOPMENT. • 467

Hypothermia is a major determinant of cerebrovascular resistance in infants during hypothermic cardiopulmonary bypass(HCPB). We recently reported a protein tyrosine kinase(PTK)-dependent pathway as a basis for cold-induced contraction (CIC) in newborn lamb MCA. Since cerebrovascular reactivity changes markedly during development, we examined, using tissue bath technique, CIC (bath temperature=21°C) of MCAs isolated from fetal sheep[fMCA](<110 days gestation, n=14) and adult sheep[aMCA] (n=4) for comparison to previously published data from newborn lambs[nMCA] (2-7 days, n=60). Compared to nMCA (KCl=2.79±0.14; CIC=1.38±0.12 g), aMCAs exhibited significantly greater contractile force in response to both KCl and cold stimulus (KCl=5.84±0.30;CIC=2.25±0.20 g) while fMCAs generated less contractile force in response to both KCl stimulus and cold stimulus(KCl=1.51±0.10;CIC-0.27±0.05 g). When normalized relative to the KCl-induced contraction, the fMCA CIC was significantly less than nMCA and aMCA (18±3%, 55±3%, and 39±4% of the maximal response to KCl, respectively; p<0.05). Interestingly, sodium orthovanadate (100μM), an inhibitor of protein tyrosine phosphatase(PTP), greatly potentiated the CIC of fMCA (>100%KCl). Since fMCAs contract more vigorously to norepinephrine than nMCA, the diminished CIC of fMCA is not due to the inability of fMCA to respond to contractile stimuli. The data suggest that factors regulating CIC of MCA during are age-dependent. We speculate that this may involve expression of PTK and/or PTP-associated pathways and may be relevant during HCPB procedures in very young infants and associated neurological sequelae.{Supported by American Heart Association national council, #95009270}

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Wagerle, L., Kim, S. & Russo, P. DIFFERENTIAL CONTRACTILE RESPONSE OF MIDDLE CEREBRAL ARTERY(MCA) TO HYPOTHERMIA DURING PERINATAL DEVELOPMENT. • 467. Pediatr Res 39, 80 (1996). https://doi.org/10.1203/00006450-199604001-00487

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