iloprost and Endotoxemia

To investigate that exogenous prostacyclin would counterbalance an endotoxemia-induced intrarenal vasoconstriction and would therefore have beneficial effects on kidney function.. Prospective, randomized, controlled study.. University medical center research laboratory.. Eighteen male Wistar rats.. In anesthetized and ventilated animals, arterial blood pressure (mean arterial blood pressure [MAP]) and renal blood flow (RBF) were recorded. Renal microvascular Po2 (muPo2) and renal venous Po2 were continuously measured by phosphorescence lifetime technique. All animals received a 30-minute infusion of lipopolysaccharide (LPS) (2.5 mg/kg) to induce endotoxemia. One group of rats was not resuscitated. A second group received fluid resuscitation 90 minutes after stop of LPS infusion. In a third group of rats, the prostacyclin analogue iloprost (100 ng/kg/min) was continuously infused in addition to fluid resuscitation. Furthermore, in all the animals, plasma NOx levels, renal inducible nitric-oxide synthase (iNOS) messenger RNA (mRNA) expression, and creatinine clearance were determined.. During LPS infusion, MAP and RBF progressively dropped to 50% of baseline at 120 minutes. After an initial increase in MAP and RBF, start of fluid resuscitation with iloprost resulted in the stabilization of both parameters. All animals became anuric during endotoxemia. Only in animals receiving iloprost was creatinine clearance totally restored at the end of the experiment. Iloprost had no significant effects on average muPo2, but prevented the occurrence of cortical microcirculatory hypoxic areas. NOx levels and iNOS mRNA expression were significantly increased in all animals receiving LPS after 5 hours. There was no difference in NOx concentration between the different groups. In animals receiving iloprost, iNOS mRNA expression was significantly suppressed in the inner medulla.. Iloprost significantly restored kidney function of endotoxemic rats to baseline values. This beneficial effect of iloprost on renal function might be addressed to an improvement in intrarenal oxygenation.

Topics: Acute Kidney Injury; Animals; Endotoxemia; Iloprost; Kidney; Male; Oxygen; Rats; Rats, Wistar; Recovery of Function; Vasodilator Agents

To investigate the effects of iloprost, a stable prostacyclin analog, on leukocyte adherence in intestinal venules and intestinal microvascular blood flow in experimental endotoxemia.. Prospective, randomized, controlled animal study.. Experimental laboratory.. Twenty-one male Wistar rats weighing 190 +/- 40 g.. The rats were divided equally into three groups: the first was a control group; the second received endotoxin (20 mg/kg lipopolysaccharide from Escherichia coli O55:B5 intravenously); and the third received endotoxin and intravenous iloprost infusion (2 ng.kg-1.min-1).. The distal small intestine of the animals was examined by using intravital fluorescence videomicroscopy 2 hrs after endotoxin challenge. Leukocytes were stained in vivo by means of rhodamine 6G. Intestinal microvascular blood flow was measured by laser Doppler flowmetry in the terminal ileum. Iloprost treatment significantly attenuated the count of adherent leukocytes in collecting venules (control, 61 +/- 10 n/mm2; lipopolysaccharide, 364 +/- 60 n/mm2; iloprost, 232 +/- 29 n/mm2; p <.05) and in postcapillary venules (control, 96 +/- 14 n/mm2; lipopolysaccharide, 470 +/- 21 n/mm2; iloprost 390 +/- 41 n/mm2; p <.05). Intestinal microvascular blood flow was decreased significantly in the lipopolysaccharide group (-49%), whereas iloprost-treated animals showed no significant difference compared with the control group.. The study demonstrated that administration of iloprost attenuated leukocyte adherence in postcapillary and collecting intestinal venules and improved intestinal microvascular blood flow. Thus, iloprost treatment may impact endotoxin-induced intestinal injury.

Topics: Analysis of Variance; Animals; Blood Flow Velocity; Cell Adhesion; Endotoxemia; Hemodynamics; Iloprost; Intestine, Small; Laser-Doppler Flowmetry; Leukocytes; Male; Microcirculation; Microscopy, Fluorescence; Microscopy, Video; Platelet Aggregation Inhibitors; Prospective Studies; Rats; Rats, Wistar

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

To determine the effects of the stable prostacyclin analog, iloprost, in a porcine model of endotoxin-induced mesenteric ischemia.. Prospective, experimental, randomized, controlled study.. Animal research laboratory at a university medical center.. Pigs were randomized to receive a constant infusion of iloprost (0.18 microg/kg/min) or an equivalent amount of carrier solution (normal saline) 30 mins before being infused with endotoxin (100 microg/kg over 1 hr). The infusion with iloprost or carrier solution was continued for the duration of the experiment.. Twelve pigs (six per group), weighing between 20 and 22 kg, underwent laparotomy during which a magnetic flowprobe was placed around the superior mesenteric artery and an ileal tonometer was inserted. Thirty minutes before they were infused with endotoxin, the animals were randomized to receive intravenous iloprost or normal saline. Endotoxin was infused centrally over a 60-min period. Animals received normal saline at a rate of 1.2 mL/kg/min which was begun at the start of the endotoxin infusion. Data were measured at the end of the endotoxin infusion (E60) and 1 hr later (E120). Mean arterial pressure was not affected by the dosage of iloprost used in this experiment. After resuscitation, the cardiac output returned to baseline in the iloprost-treated group but remained decreased in the control group (2.6 +/- 0.5 vs. 1.6 +/- 0.4 L/min). Superior mesenteric blood flow increased 34% above baseline levels in animals pretreated with iloprost (from 363 +/- 85 to 485 +/- 81 mL/min). The superior mesenteric PCO2 was significantly higher (53 +/- 9 vs. 40 +/- 5 torr; 7.1 +/- 1.2 vs. 5.3 +/- 0.7 kPa) and the ileal intramucosal pH was significantly lower (7.07 +/- .28 vs. 7.44 +/- .23) in the control group than in the iloprost-treated group.. Pretreatment with intravenous iloprost effectively increased intestinal blood flow in this model of endotoxin-induced mesenteric ischemia. This action of the drug resulted in an attenuation of ileal intracellular acidosis. Since low-dose iloprost had no effect on mean arterial pressure, it may be a useful adjunct in the treatment of sepsis and septic shock.

Topics: Acidosis; Animals; Endotoxemia; Evaluation Studies as Topic; Hemodynamics; Iloprost; Intestines; Ischemia; Prospective Studies; Random Allocation; Splanchnic Circulation; Swine; Vasodilator Agents