title: Hemodynamic homeostasis during acute hypoxia in septic and nonseptic piglets: differential role of prostaglandins and nitric oxide.
abstract: We studied the hemodynamic responses of 29 anesthetized and mechanically ventilated piglets to acute hypoxia [reduction of Pao2 from 130 to 38 mm Hg induced by inhalation of 7% fraction of inspired oxygen (Fio2) for 7.5 min] before and during group B beta-hemolytic streptococci (GBS) sepsis. During hypoxia, nonseptic piglets maintained stable systemic blood pressure [105+/-9 (SD) to 97+/-14 mm Hg] and cardiac output (CO) (667+/-72 to 685+/-113 mL/min). However, during GBS/hypoxia, systemic blood pressure fell from 94+/-17 to 49+/-25 mm Hg, CO fell from 397+/-146 to 223+/-142 mL/min (both p < 0.001 versus pre-GBS), and cardiac arrest often ensued. We tested three hypotheses that might underlie GBS-induced intolerance to systemic hypoxia: 1) GBS-induced reduction of systemic CO/systemic oxygen delivery (QO2) below a critical QO2 beyond which the superimposition of hypoxia becomes intolerable; this mechanism is unlikely as nonseptic piglets with comparable reductions in CO/QO2 (induced by inflation of a left atrial balloon) tolerated hypoxia well; 2) GBS-induced inhibition of nitric oxide (NO) synthesis that is vital to tolerance of hypoxia; this mechanism is unlikely as infusion of the NO substrate L-arginine did not restore tolerance to hypoxia during GBS infusion (as it did after inhibition of NO synthesis during infusion of N-nitro-L-arginine in nonseptic piglets); and 3) GBS-induced production of pathologic prostaglandins that impaired the piglet's capacity to tolerate hypoxia; this mechanism finds support in the observation that inhibition of prostaglandins with the cyclooxygenase inhibitor indomethacin completely restored the ability of septic piglets to tolerate hypoxia. Further evaluation of GBS-induced intolerance to systemic hypoxia may provide insight into the incompletely understood mechanisms by which sepsis induces circulatory collapse in experimental animals and in humans.
authors.affiliation: Department of Pediatrics, Rush Medical Center, Chicago, Illinois, USA.
authors.forename: B
authors.initials: B
authors.lastname: Rudinsky
authors.forename: R
authors.initials: R
authors.lastname: Hipps
authors.forename: A
authors.initials: A
authors.lastname: Bell
authors.forename: M
authors.initials: M
authors.lastname: Lozon
authors.forename: W
authors.initials: W
authors.lastname: Meadow
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D006439:Hemodynamics; D006706:Homeostasis; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D018805:Sepsis / Q000503:physiopathology*; D013290:Streptococcal Infections / Q000503:physiopathology*; D013552:Swine
chemical_list: D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin