iloprost and Escherichia-coli-Infections

To compare the effects of a 12 h continuous infusion of iloprost, a stable prostacyclin analogue, on hepatic blood flow (Qliv), O2 exchange, and energy metabolism during a 24 h hyperdynamic, porcine endotoxemia with volume resuscitation alone.. Prospective, randomized, experimental study with repeated measures.. Investigational animal laboratory.. Twenty-eight domestic pigs: 16 animals during endotoxemia with volume resuscitation alone (ETX), 12 with endotoxemia, volume resuscitation, and treatment with iloprost (ILO).. Endotoxemia was initiated by continuous infusion of E. coli lipopolysaccharide. Animals were resuscitated with hetastarch, aimed at maintaining a MAP of > 60 mmHg. After 12 h of endotoxemia, iloprost was administered for 12 h in the treatment group, titrated to avoid pharmacologically induced hypotension (MAP < 60 mmHg).. Iloprost significantly increased Qliv, with no effect on hepatic O2 delivery. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface, as well as HbScO2 frequency distributions--a measure of microcirculatory O2 availability--remained unchanged. Treatment with iloprost, however, significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased endogenous glucose production (EGP) rate, iloprost restored EGP to normal at the end of the experiment.. Thus, in a clinically relevant model of human sepsis, iloprost did not produce potential adverse effects but rather ameliorated hepatic metabolic disturbances and, thereby, hepatic energy balance.

Topics: Animals; Blood Gas Analysis; Disease Models, Animal; Drug Evaluation, Preclinical; Endotoxemia; Energy Metabolism; Escherichia coli; Escherichia coli Infections; Female; Fluid Therapy; Hemodynamics; Hemoglobins; Iloprost; Lactic Acid; Lipopolysaccharides; Liver; Male; Microcirculation; Oxygen Consumption; Prospective Studies; Pyruvic Acid; Random Allocation; Resuscitation; Swine; Time Factors; Vasodilator Agents

Septic shock was induced by intravenous infusion of live Escherichia coli in pigs to investigate the influences on central hemodynamic, coagulation, and fibrinolytic reactions by a thromboxane A2 (TxA2)-receptor blocker (BM 13.177; n = 6) and a prostacyclin analogue (iloprost or ZK 36,374; n = 7). The early pulmonary vasoconstriction following E coli infusion was attenuated, but not abolished, by BM 13.177. Only minor effects were seen after pretreatment with iloprost. Neither drug had any major effect on the coagulation and fibrinolytic activation. These results confirm that TxA2 is an important, but not the only, mediator of early pulmonary vascular response in porcine septicemia and that neither TxA2 nor prostacyclin is of major importance for the hemostatic reactions in this shock model.

Topics: Animals; Blood Pressure; Epoprostenol; Escherichia coli Infections; Female; Hemodynamics; Hemostasis; Iloprost; Male; Platelet Aggregation; Pulmonary Circulation; Receptors, Prostaglandin; Receptors, Thromboxane; Shock, Septic; Sulfonamides; Vascular Resistance