Abstract 1615 Neonatal Infectious Disease Platform, Monday, 5/3

Introduction: Reduced cerebral blood flow (CBF) occurs in neonatal bacterial meningitis (BM) and is associated with increased intracranial pressure (McMenamin and Volpe, 1984). Reduced CBF in BM is probably multifactorial and has been shown in experimental BM in the adult rabbit to be associated with increased cerebrovascular resistance (ICVR) (Tureen, 1995). Endothelin, a vasoconstrictor peptide is a candidate mediator of ICVR in BM. Hypothesis: Inhibition of endothelin resulting in increased CBF would support ICVR as a mechanism of reduced CBF in BM. Materials and Methods: Twelve-day-old (P12) Sprague-Dawley rats were given meningitis by intracisternal injection of log10 4.0 colony-forming units of Streptococcus pneumoniae, type 3. Animals were randomly assigned to three groups - uninfected controls, infected, and infected plus bosantin (30 mg/kg/d sq), an endothelin receptor antagonist. CBF was measured at 18h of infection by a modification of the reference method for measurement of organ blood flow (Heymann, 1977) using 10μ fluorescent microspheres injected intracardiac. Cerebrospinal (CSF) fluid lactate and glucose were also measured at 18h. Results (Mean ± SD) are shown below (* p < .05 vs infected plus bosantin): (Table) Conclusions : Endothelin inhibition in P12 rats with experimental BM led to increased CBF and decreased CSF lactate, a marker for anaerobic metabolism. These findings suggest that ICVR plays a role in cerebral ischemia in BM which is mediated by endothelin.

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