iloprost and Pulmonary-Edema

Although inhaled NO (iNO) has been shown to lower pulmonary pressures and edema accumulation in experimental acute lung injury, its clinical use has been questioned because of a lack of improvement in outcome, rebound phenomena, and potential toxicity. We investigated the effects of aerosolized iloprost, a stable prostacyclin analogue, compared with iNO on pulmonary pressures and lung edema in 20 female sheep with oleic acid lung injury. The most effective dose of iloprost was determined in healthy animals before the experiment. Anesthetized and ventilated sheep received a central venous oleic acid infusion and were continuously infused with Ringer lactate to achieve a positive fluid balance (5 mL.kg(-1).h(-1)). In the iNO group (n = 6), iNO (20 ppm) was administered continuously for 8 h. Animals in the iloprost group (n = 6) received aerosolized iloprost (40 microg 2 h(-1)). Animals in the control group (n = 6) had no further intervention. Oleic acid infusion was associated with impaired oxygenation, pulmonary hypertension, and lung edema in all groups. Although iNO significantly decreased pulmonary vascular resistance index, effective pulmonary capillary pressure, and extravascular lung water index, these parameters were unaffected by iloprost. Oxygenation index (Pao2/Fio2) increased significantly both during NO and iloprost inhalation but also tended to improve in the control group over time. In contrast to iNO, the investigated dose of iloprost was ineffective to attenuate acute lung injury-induced changes in pulmonary hemodynamics and lung edema in this experimental model.

Topics: Administration, Inhalation; Aerosols; Animals; Female; Iloprost; Lung Injury; Nitric Oxide; Oleic Acid; Pulmonary Circulation; Pulmonary Edema; Sheep

This case report describes the treatment of reperfusion lung oedema after pulmonary thromboendarterectomy using intravenous iloprost infusion in a 52-year-old woman diagnosed with chronic thromboembolic pulmonary hypertension.

Topics: Endarterectomy; Female; Humans; Hypertension, Pulmonary; Iloprost; Infusions, Intravenous; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Pulmonary Edema; Pulmonary Embolism; Reperfusion Injury

The objectives of this study were to compare the protective effects of ascorbic acid and iloprost on lung injury caused by ischemia reperfusion (I/R) of the lower extremities of rats. Wistar albino rats (n = 34) were divided into five groups. In the I/R group (n = 6), the aorta was cross-clamped for 3 hr, followed by 1 hr of reperfusion. In the vitamin C group (n = 8), animals were pretreated with 100 mg/kg ascorbic acid via the left jugular vein before aortic cross-clamping. In the iloprost group (n = 8), animals were pretreated with 20 ng/(kg x min) iloprost by constant intravenous infusion via the left jugular venous cannula. In the sham group (n = 6), the abdomen was left open at the same period and a juguler venous line was established. In the control group (n = 6), lungs were removed and blood samples taken immediately after sternotomy. No treatment was given in this group. After both lungs were removed, biochemical parameters were measured and histopathological evaluation was made. Although the arterial blood pO2 and HCO3 levels were statistically significantly high in both the vitamin C and iloprost groups compared to the I/R group, plasma malondialdehyde (MDA) levels were significantly low. Meanwhile, the MDA levels in the lung tissue were significantly low in the vitamin C group compared to the I/R group. The MDA level in the lung tissue in the iloprost group was also low compared to the I/R group, but it was not statistically significant. The lungs of the I/R group displayed intense interstitial leukocytic infiltration in histopathological examination compared to the other groups. Pretreatment of animals with iloprost and vitamin C significantly decreased the pulmonary injury characterized by decreased plasma leukocyte sequestration. The results suggest that both vitamin C and iloprost are useful agents for attenuating the lung injury caused by increased oxidative stress and neutrophil accumulation after a period of I/R of the lower extremities.

Topics: Animals; Aorta, Abdominal; Ascorbic Acid; Constriction; Disease Models, Animal; Free Radical Scavengers; Iloprost; Lipid Peroxidation; Lung; Neutrophils; Platelet Aggregation Inhibitors; Pulmonary Edema; Rats; Rats, Wistar; Reperfusion Injury

The local ischemia-reperfusion (I/R) process gains a systemic nature and affects distal organs. The remote effects of I/R are most frequently observed in the lungs and pulmonary damage may vary from acute lung injury with mild dysfunction to severe respiratory failure or the acute respiratory distress syndrome. In this hind limb I/R induced experimental lung injury model two groups of rats as IR and ILO were determined. Both groups underwent 60 min of ischemia and 120 min of reperfusion. While ILO group received iloprost in saline, IR group received only saline before reperfusion period intravenously. Serum myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels and total antioxidant capacity (TAC) and lung tissue MPO activity, MDA levels and Na+-K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The MPO activities in serum and lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01). The MDA levels in lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01), but the decreases were not significant in serum MDA levels (P=0.052). Serum TAC and lung tissue Na+-K+ ATPase activity levels were found to be increased in ILO group compared to IR group (P < or = 0.01). Lung histology showed marked improvement by iloprost compared to the IR group in this study. Iloprost has been found to be effective in attenuating ischemia reperfusion-induced remote organ damage, in this case, lung injury, in rats.

Topics: Acute Disease; Adenosine Triphosphatases; Animals; Antioxidants; Cation Transport Proteins; Hindlimb; Iloprost; Male; Malondialdehyde; Neutrophil Infiltration; Peroxidase; Pulmonary Alveoli; Pulmonary Edema; Rats; Rats, Wistar; Reperfusion Injury; Respiratory Insufficiency; Sodium-Potassium-Exchanging ATPase; Vasodilator Agents

Lung transplantation is effective for end-stage pulmonary disease, but its successful application is still limited by organ shortage and sub-optimal preservation techniques. Therefore, optimal allograft protection is essential to reduce organ dysfunction, especially in the early post-operative period. Intravenous prostanoids are routinely used to ameliorate reperfusion injury. However, the latest evidence suggests similar efficacy using inhaled prostacyclin. Thus, we evaluated the impact of donor pre-treatment using the prostacyclin analog, iloprost, on post-ischemic function of Perfadex-protected allografts.. In Group 1, 5 pig lungs were preserved with Perfadex (PER group) solution and stored for 27 hours. In Group 2, 100 microg of iloprost was aerosolized over 30 minutes using a novel mobile ultrasonic nebulizer (Optineb) before identical organ harvest (PER-ILO group). After left lung transplantation and contralateral lung exclusion, hemodynamic variables, Po2/Fio2 and dynamic compliance were monitored for 6 hours and compared with sham-operated controls. Pulmonary edema was determined stereologically and by wet-to-dry (W/D) weight ratio. Statistical assessment included analysis of variance (ANOVA) with repeated measures.. Dynamic compliance and pulmonary vascular resistance (PVR) were superior in iloprost-treated compared with untreated organs (p < 0.05), whereas oxygenation was comparable between groups. W/D ratio revealed a significantly smaller amount of lung water in PER-ILO organs (p = 0.048), whereas stereologic data showed a trend toward less intra-alveolar edema.. Endobronchial application of iloprost in donor lungs before Perfadex preservation decreases post-ischemic edema and significantly improves lung compliance and vascular resistance. This innovative approach is easily applicable in the clinical setting and offers a new strategy for improvement of pulmonary allograft preservation.

Topics: Administration, Inhalation; Animals; Female; Iloprost; Lung Compliance; Lung Diseases; Lung Transplantation; Models, Animal; Nebulizers and Vaporizers; Organ Preservation; Preoperative Care; Pulmonary Edema; Reperfusion Injury; Swine; Tissue Donors; Vascular Resistance; Vasodilator Agents

Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance.. In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-).. Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group.. We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

Topics: Animals; Body Weight; Disease Models, Animal; Endothelin-1; Iloprost; Lung; Male; Models, Cardiovascular; Oxygen; Pulmonary Circulation; Pulmonary Edema; Pulmonary Gas Exchange; Pulmonary Wedge Pressure; Rats; Rats, Inbred Lew; Reperfusion Injury; Respiratory Distress Syndrome; Severity of Illness Index; Statistics as Topic; Vascular Resistance; Vasodilator Agents

Isolated lungs from male Wistar rats (250-350 g) were perfused at a constant flow rate (10 ml/min, non-recirculating) with Krebs-Ringer-bicarbonate buffer containing 4.5 % bovine serum albumin, and were ventilated at a positive pressure (60 breaths/min). Pulmonary arterial pressure and lung weight (as a measure of edema formation) were recorded continuously. After an equilibration period of 20 minutes the various test compounds were added to the perfusion fluid and experimental recording was continued for another 60 minutes. The effects of the stable PGI2-mimetic, iloprost, of PGE1, and of the biologically active PGE1-metabolite, 13,14-dihydro-PGE1, were evaluated in this model (n = 6). Iloprost showed slight, but not significant vasodilation; however, lung weight remained unchanged. PGE1 and 13, 14-dihydro-PGE1 also caused slight vasodilation, but in contrast to iloprost these compounds induced distinct pulmonary edema. The lung weight gain was discernible at concentrations of 2.8 x 10(-6) mol/l (significant at 2.8 x 10(-5) mol/l; p < or = 0.05) and was accompanied by increases in the wet-weight to dry-weight ratios. These findings were duplicated in a second set of experiments (n = 6) from which the same results were obtained. The results indicate that at high concentrations PGE1 (and 13,14-dihydro-PGE1), but not iloprost, can induce pulmonary edema in rats probably by increasing the permeability of the pulmonary vasculature.

Topics: Alprostadil; Animals; Blood Pressure; Disease Models, Animal; Iloprost; In Vitro Techniques; Male; Organ Size; Perfusion; Pulmonary Artery; Pulmonary Edema; Rats; Rats, Wistar; Reproducibility of Results; Vasodilator Agents

Accumulation of radioisotope labelled transferrin in the lungs of guinea pigs was determined with an external detection system. The method is based on the intravascular and extravascular distribution of indium-113m labelled transferrin compared with the intravascular distribution of technetium-99m labelled red blood cells. Guinea pigs were given iloprost, a prostacyclin analogue and potent pulmonary vasodilator, and noradrenaline, a pulmonary vasoconstrictor, in an attempt to increase and decrease respectively the blood volume in the lungs. Neither agent altered transferrin accumulation in the lung by comparison with a saline infusion. Iloprost infused before and after oleic acid infusion reduced macro-molecular leakage when compared with oleic acid alone. These data suggest that the double isotope method can distinguish between hydrostatic and injury induced pulmonary oedema.

Topics: Animals; Cardiovascular Agents; Erythrocytes; Guinea Pigs; Iloprost; Indium Radioisotopes; Lung; Male; Norepinephrine; Oleic Acid; Oleic Acids; Pulmonary Edema; Radionuclide Imaging; Technetium; Transferrin

The effect of thromboxane A2 inhibitors and iloprost, a stable analogue of prostacyclin, on angiotensin II-induced oedema was studied in the isolated perfused rat lung. Angiotensin II, infused into the pulmonary artery, produced oedema of the lung, as evidenced by the increase in lung weight and in perfusion pressure. UK 38485, a thromboxane A2-synthetase inhibitor, and BM 13177, a thromboxane A2 receptor blocker, attenuated the oedema producing and vasoconstrictor effects of angiotensin II. A similar effect was obtained with iloprost at very low concentrations. Other agonists such as noradrenaline, phenylephrine and high K+ in the medium produced increases in perfusion pressure, but failed to elicit an increase in lung weight. Only serotonin, at relatively higher concentrations again increased lung weight, which was prevented by prior addition of UK 38485, BM 13177 and iloprost into the medium. These results were taken as an evidence indicating thromboxane A2 and prostacyclin-mediated effects of angiotensin II in the isolated perfused rat lung and the possible role of these unstable metabolites of arachidonic acid in the production of lung oedema.

Topics: Angiotensin II; Animals; Anti-Arrhythmia Agents; Blood Pressure; Catecholamines; Epoprostenol; Female; Iloprost; Imidazoles; In Vitro Techniques; Lung; Male; Organ Size; Pulmonary Edema; Rats; Serotonin; Thromboxane A2; Thromboxane-A Synthase