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 ha ve 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 de livery (DO2) during an acute reduction in blood flow induced by cardia c tamponade in endotoxic dogs. Thirty anesthetized, ventilated dogs we re divided into three groups. A first group (N = 10) served as a contr ol 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 infusi on. 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 ther apy, Escherichia coli endotoxin (2 mg/kg) was injected in each dog. In each group, the administration of PGE(1), fluids, or both was continu ed throughout the study. Tamponade was then induced by repeated bolus injections of warm saline into the pericardial space. Steady-state mea surements 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 volu me 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 identic al. 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 (b oth P < 0.05). Critical oxygen extraction ratio (O(2)ER(crit)) which w as 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 (bo th P < 0.05). To investigate whether PGE(1) also improves oxygen extra ction capabilities in the absence of endotoxin, a second series of exp eriments 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 th e control group (NS). O(2)ER(crit) tended to be higher in the PGE(1) g roup than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.0 54). In conclusion, PGE(1) could almost entirely restore tissue oxygen extraction capabilities after endotoxin challenge on this dog model i n which cardiac index was acutely reduced. The effects on oxygen extra ction were present with or without concurrent saline administration, b ut the combination of PGE(1) with fluids improved global hemodynamics. Under control conditions, the influence of PGE(1) on the tissue oxyge n extraction capabilities was not significant. (C) 1994 Academic Press , Inc.