VASODILATING PROSTAGLANDIN-E1 DECREASES CRITICAL OXYGEN DELIVERY BY INCREASING CRITICAL OXYGEN EXTRACTION IN ANESTHETIZED PIGS

The abnormal dependence of O2 uptake (VO2) on O2 delivery (QO2) during severe sepsis, and the adult respiratory distress syndrome (ARDS) may be caused by impaired vascular reactivity, following release of vasod ilating prostaglandins. Infusion of these compounds, however, may impr ove tissue oxygenation. We studied the effect of vasodilating prostagl andin E1 (PGE1; 0.2 mug/kg/min) on the critical O2 extraction ratio (E RO2c) and the critical QO2 (QO2c) in a saline-controlled, crossover st udy in 12 barbiturate-anesthetized pigs. QO2, VO2 (independently from QO2), and blood lactate concentrations were measured during graded car diac output reductions by incremental positive end-expiratory pressure (0-20 cm H2O PEEP, raised by 5 cm H2O at 15 min intervals). At 0 cm H 2O PEEP, PGE1 decreased arterial blood pressure, mainly due to a fall in systemic vascular resistance. From 0 to 20 cm H2O PEEP, the fall in QO2 was greater in the PGE1 than in the saline series (P < 0.005), si nce ventricular filling and the rise in heart rate were less in the fo rmer. The decrease in VO2 (P < 0.005) did not differ between series. A s estimated from bilinear regression on paired VO2/QO2 data in individ ual pigs, the QO2c was 9.8 +/- 3.6 (mean +/- SD) during PGE1 and 14.6 +/- 3.8 ml/kg/min during saline infusion (P = 0.008), with ERO2c 68% /- 16% and 48% +/- 12%, respectively (P < 0.005). The QO2c, estimated from bilinear regression on paired lactate/QO2 data during the first t reatment period, was 7.1 +/- 1.2 for PGE, and 12.8 +/- 4.5 ml/kg/min f or saline (P < 0.05), at similar lactate concentrations (2.0 +/- 0.5 a nd 1.7 +/- 0.5 mmol/liter, respectively). PGE1-induced vasodilation th us decreases QO2c, because of increased ERO2c, probably resulting from capillary recruitment, an increased surface area available for O2 exc hange, and decreased O2 diffusion distances. Hence, a reduced ERO2 and abnormal supply dependence of VO2 during severe sepsis and ARDS are n ot caused by release of vasodilating prostaglandins. In contrast, our results partly explain improved tissue oxygenation with these compound s during abnormal VO2 supply dependence, following sepsis and ARDS.