We investigated whether group B streptococcal (STREP) infusion impairs the cerebral blood flow (CBF) response to acute hypercarbia in piglets, and whether STREP-induced prostanoids or hemodynamic alterations could account for this impairment. Piglets, 2-3 wk old, were anesthetized, paralyzed, and mechanically ventilated (50% O2; partial pressure of arterial CO2(Paco2) ≈ 40 torr). CBF was assessed by internal carotid artery blood flow (ICBF). Group 1 (n= 5) received a continuous infusion of STREP for 4 h (2.0-8.0 × 107org/kg-min). Group 2(n= 5) was pretreated with indomethacin (5 mg/kg), then received the identical STREP infusion. Group 3 (n= 6) did not receive STREP, but cardiac output (CO) and systemic blood pressure (BP) were reduced to levels equal to that of group 1 by incremental inflation of a left atrial balloon (LAB) catheter. Cerebral vascular reactivity to acute hypercarbia(Paco2≈ 70 torr for 7.5 min) was assessed at baseline and after each hour of STREP infusion or LAB inflation. We found that 4 h of STREP infusion caused CO to fall significantly (634 ± 121 to 324 ± 172 mL/min, group 1; 600 ± 68 to 291 ± 80 mL/min, group 2) and BP to fall significantly (104 ± 20 to 57 ± 4 mm Hg, group 1; 91± 11 to 53 ± 16 mm Hg, group 2) By design, in group 3 LAB inflation caused CO (573 ± 181 to 375 ± 159 mL/min) and BP (104± 14 to 60 ± 9 mm Hg) to fall to values not significantly different from septic groups 1 and 2. At 4 h, unilateral ICBF decreased significantly during STREP infusion in group 1 (32.0 ± 10.8 to 21.0± 7.3 mL/min) and group 2 (22.9 ± 9.9 to 13.1 ± 4.3 mL/min), but not in nonseptic group 3 (23.1 ± 7.4 to 19.6 ± 6.3 mL/min). At baseline, hypercarbia induced an increase in ICBF (%ΔICBF = 68.7 ± 13.0% in group 1, 62.2 ± 15.6% in group 2, and 87.7± 34.0% in group 3). After 4 h of STREP, this response was completely ablated as ICBF fell during hypercarbia by -7.8 ± 23.2% (group 1). Indomethacin did not protect cerebral vascular reactivity after 4 h of STREP infusion, as%ΔICBF fell during hypercarbia by -10.9 ± 17.7%(group 2). In contrast, despite equivalent reductions in CO and BP after 4 h of LAB inflation in nonseptic group 3, ICBF rose during hypercarbia by 61.8± 23.2%, not significantly different from baseline, but significantly different from the decrease in%ΔICBF in groups 1 and 2. We conclude that STREP infusion reduces ICBF and cerebral vascular reactivity to acute hypercarbia in piglets. This phenomenon is not accounted for by STREP-induced reduction in CO or BP, and is not mediated by prostanoids.Abbreviations: STREP,group B Streptococcus;CBF,cerebral blood flow;LAB,left atrial ballon;ICBF,internal carotid artery blood flow;CO,cardiac output;PA,pulmonary artery;PAP,pulmonary artery pressure;BP,systemic blood pressure;EDRF,endothelium-derived relaxation factor;CVP,central venous pressure;SSP,sagittal sinus pressure;RMANOVA,repeated measures analysis of variance;Pao2,partial pressure of arterial O2;Paco2,partial pressure of arterial CO2