title: Group B streptococcal sepsis impairs cerebral vascular reactivity to acute hypercarbia in piglets.
abstract: 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) approximately 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 x 10(7) org/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 approximately 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 (% delta ICBF = 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 % delta ICBF 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 % delta ICBF 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.
authors.affiliation: Department of Pediatrics, University of Chicago, Illinois 60637, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Rudinsky
authors.forename: M
authors.initials: M
authors.lastname: Lozon
authors.forename: A
authors.initials: A
authors.lastname: Bell
authors.forename: R
authors.initials: R
authors.lastname: Hipps
authors.forename: W L
authors.initials: WL
authors.lastname: Meadow
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D002248:Carbon Monoxide / Q000378:metabolism; D002343:Carotid Artery, Internal / Q000502:physiology; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology; D011652:Pulmonary Circulation; D018805:Sepsis / Q000503:physiopathology*; D013290:Streptococcal Infections / Q000503:physiopathology*; D013292:Streptococcus agalactiae / Q000378:metabolism*; D013552:Swine
chemical_list: D002248:Carbon Monoxide; D007213:Indomethacin