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 Pao2from 130 to 38 mm Hg induced by inhalation of 7% fraction of inspired oxygen (Fio2) for 7.5 min) before and during group B -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 (bothp“ 0.001versuspre-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 QO2beyond 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 ofN-nitro-l-arginine in nonseptic piglets); and3) 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.© International Pediatrics Research Foundation, Inc. 2000. All Rights Reserved.