PROSTAGLANDIN E(1) INCREASES OXYGEN EXTRACTION CAPABILITIES IN EXPERIMENTAL SEPSIS

By its microvascular and anti-inflammatory actions, prostaglandin E(1) (PGE(1)) has been suggested both in animal models and in humans to have a therapeutic value in sepsis. To investigate whether PGE(1) could improve the oxygen extraction capabilities in severe sepsis, our study focused on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow induced by cardiac tamponade in endotoxic dogs. Thirty anesthetized, ventilated dogs were divided into three groups. A first group (N = 10) served as a control receiving 20 ml/kg/hr of saline intravenously. A second group (N = 10) received PGE(1) at 100 ng/kg/min along with the same saline infusion. A third group (N = 10) received the same dose of PGE(1) with only 1 ml/kg/hr of saline. Thirty minutes after the initiation of this therapy, Escherichia coli endotoxin (2 mg/kg) was injected in each dog. In each group, the administration of PGE(1), fluids, or both was continued throughout the study. Tamponade was then induced by repeated bolus injections of warm saline into the pericardial space. Steady-state measurements of VO2 (derived from the expired gases) and DO2 (the product of cardiac index and oxygen content) were obtained sequentially after each saline injection. The administration of PGE(1) + fluids resulted in significant increases in stroke volume, cardiac index, and DO2 and reductions in systemic and pulmonary vascular resistance. Stroke volume and cardiac index were lower in the PGE(1) alone than in the PGE(1) + fluids group. The VO2 levels at critical DO2 (DO2crit) were identical. However, DO2crit, which was 12.2 +/- 2.8 ml/kg/min in the control group, was significantly decreased to 9.8 +/- 2.0 ml/kg/min in the PGE(1) + fluids and to 9.3 +/- 2.7 ml/kg/min in the PGE(1) alone group (both P < 0.05). Critical oxygen extraction ratio (O(2)ER(crit)) which was 47 +/- 14% in the control group, was increased to 63 +/- 16% in the PGE(1) + fluids group and to 61 +/- 17% in the PGE(1) alone group (both P < 0.05). To investigate whether PGE(1) also improves oxygen extraction capabilities in the absence of endotoxin, a second series of experiments was performed in 14 dogs, receiving saline alone (Control, N = 7) or plus PGE(1) at 100 ng/kg/min (PGE(1), N = 7). DO2crit was 10.7 +/- 2.9 ml/kg/min in the PGE(1) group vs 10.1 +/- 1.8 ml/kg/min in the control group (NS). O(2)ER(crit) tended to be higher in the PGE(1) group than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.054). In conclusion, PGE(1) could almost entirely restore tissue oxygen extraction capabilities after endotoxin challenge on this dog model in which cardiac index was acutely reduced. The effects on oxygen extraction were present with or without concurrent saline administration, but the combination of PGE(1) with fluids improved global hemodynamics. Under control conditions, the influence of PGE(1) on the tissue oxygen extraction capabilities was not significant. (C) 1994 Academic Press, Inc.