title: Prostaglandin E1 increases oxygen extraction capabilities in experimental sepsis.
abstract: By its microvascular and anti-inflammatory actions, prostaglandin E1 (PGE1) has been suggested both in animal models and in humans to have a therapeutic value in sepsis. To investigate whether PGE1 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 PGE1 at 100 ng/kg/min along with the same saline infusion. A third group (N = 10) received the same dose of PGE1 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 PGE1, 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 PGE1 + 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 PGE1 alone than in the PGE1 + 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 PGE1 + fluids and to 9.3 +/- 2.7 ml/kg/min in the PGE1 alone group (both P < 0.05). Critical oxygen extraction ratio (O2ERcrit) which was 47 +/- 14% in the control group, was increased to 63 +/- 16% in the PGE1 + fluids group and to 61 +/- 17% in the PGE1 alone group (both P < 0.05). To investigate whether PGE1 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 PGE1 at 100 ng/kg/min (PGE1, N = 7). DO2crit was 10.7 +/- 2.9 ml/kg/min in the PGE1 group vs 10.1 +/- 1.8 ml/kg/min in the control group (NS). O2ERcrit tended to be higher in the PGE1 group than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.054).(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Benlabed
authors.forename: H
authors.initials: H
authors.lastname: Spapen
authors.forename: D N
authors.initials: DN
authors.lastname: Nguyen
authors.forename: J L
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001427:Bacterial Toxins; D002305:Cardiac Tamponade / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D018805:Sepsis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli; D000527:Alprostadil; D010100:Oxygen