iloprost and Hypotension

High rate of complications has been reported following revascularization for acute limb ischemia (ALI). No adjuvant pharmacologic treatment, apart from anticoagulation and standard perioperative care, has been shown clinically effective.. Aim of this study was to evaluate the effects of the prostacyclin analog iloprost as adjuvant to surgery for ALI.. A total of 300 patients were randomly assigned to receive perioperative iloprost (intra-arterial, intraoperative bolus of 3000 ng, plus intravenous infusion of 0.5-2.0 ng/kg/min for 6 hours/day for 4-7 days following surgery), or placebo. The primary endpoint was the combined incidence of death and amputation at 3-month follow-up. Secondary endpoints were the incidence of each single major complication, total event rate, symptomatology, and tolerability.. The combined incidence of death and amputation was 19.9% in the placebo and 14.1% in the iloprost group (relative risk, 1.56; 95% confidence interval, 0.89-2.75, P = 0.12, Cox regression analysis). A statistically significant lower mortality (4.7%) was reported in patients receiving iloprost, compared with controls (10.6%; relative risk, 2.61; 95% confidence interval, 1.07-6.37, P = 0.03). The overall incidence of fatal plus major cardiovascular events was 33.1% and 22.8% in placebo and iloprost groups, respectively (relative risk, 1.61; 95% confidence interval, 1.04-2.49, P = 0.03). No serious adverse reactions occurred after iloprost administration, nor differences in the incidence of bleeding or hypotension between treatment groups.. Although at lower levels than previously reported, our results confirm the severity of ALI. Iloprost as adjuvant to surgery significantly reduced mortality and overall major event rate. Further data are needed to support this finding, and to face a still open medical issue.

Topics: Aged; Amputation, Surgical; Anticoagulants; Cause of Death; Chemotherapy, Adjuvant; Double-Blind Method; Female; Follow-Up Studies; Heparin; Humans; Hypotension; Iloprost; Infusions, Intravenous; Injections, Intra-Arterial; Ischemia; Lower Extremity; Male; Placebos; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Risk Factors; Treatment Outcome; Vasodilator Agents

Topics: Cardiovascular Agents; Epoprostenol; Humans; Hypotension; Iloprost; Male; Middle Aged; Platelet Aggregation

The authors report one case of persistent pulmonary hypertension that had hypoxia although receiving treatment with high frequency oscillation, inotropic drugs, blood transfusion, and oral sildenafil for pulmonary vasodilatation. The patient developed hypotension after two doses of oral sildenafil and no response to high dose of inotropic drugs. So aerosolized iloprost was given via endotracheal tube and oxygen saturation improved within 10 minutes. Oxygen was weaned at 36 hours after treatment with this drug and no any side effect was found.

Topics: Female; High-Frequency Ventilation; Humans; Hypotension; Iloprost; Infant, Newborn; Intubation, Intratracheal; Persistent Fetal Circulation Syndrome; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Failure; Vasodilator Agents

We attempted to determine whether activation of the sensory neuron contributes to reduction of endotoxin-induced hypotension by inhibiting tumor necrosis factor (TNF)-alpha production via calcitonin gene-related peptide (CGRP) release in rats.. Prospective, randomized, controlled study.. Research laboratory at a university medical center.. Wistar rats weighing 220-280 g.. Mean arterial blood pressure was measured in rats administered endotoxin intravenously. Animals were pretreated with capsazepine (a vanilloid receptor antagonist), CGRP(8-37) (a CGRP receptor antagonist), and indomethacin before endotoxin administration. Levels of CGRP, 6-keto-prostaglandin F1alpha, TNF-alpha, and cytokine-induced neutrophil chemoattractant (CINC) were measured by enzyme immunoassay methods. The concentration of NO2/NO3 was measured using the Griess reagent. Tissue levels of messenger RNA of the inducible form of nitric oxide synthase (iNOS) and TNF-alpha were determined by reverse transcription polymerase chain reaction.. Both lung levels of CGRP and plasma levels of 6-keto-prostaglandin F1alpha were increased after intravenous administration of endotoxin (5 mg/kg), peaking at 90 mins after endotoxin administration. Increases in plasma levels of 6-keto-prostaglandin F1alpha at 90 mins after endotoxin administration (766 +/- 134 pg/mL) were inhibited by pretreatment with capsazepine (373 +/- 44 pg/mL, p < .05), CGRP(8-37) (406 +/- 64 pg/mL, p < .05), and indomethacin (154 +/- 40 pg/mL, p < .05). Although none of the pretreatments affected a series of endotoxin-induced responses, including increases in lung tissue levels of TNF-alpha, CINC, and iNOS and the resultant hypotension in animals given 5 mg/kg endotoxin, such pretreatments enhanced these pathologic responses in animals given a smaller dose of endotoxin (1 mg/kg) to the same extent as those induced by 5 mg/kg of endotoxin, suggesting that shock responses induced by 5 mg/kg endotoxin are maximum responses and activation of sensory neurons in endotoxin-treated rats is essentially a reparative response.. Activation of sensory neurons might contribute to reduction of endotoxin-induced hypotension by releasing CGRP, which is capable of promoting endothelial production of prostacyclin.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Calcitonin Gene-Related Peptide; Capsaicin; Cyclooxygenase Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxins; Hypotension; Iloprost; Indomethacin; Interleukin-16; Lung; Neurons, Afferent; Nitric Oxide Synthase; Prospective Studies; Rats; Rats, Wistar; Reference Values; Tumor Necrosis Factor-alpha; Vasodilator Agents

The principal effects of prostaglandin I(2) are vasodilation and inhibition of platelet aggregation induced by a rise in the intracellular second messenger cAMP. In the heart a rise in intracellular myocardial cAMP increases contractility. We examined whether prostaglandin I(2) increases left ventricular contractility in vivo. The effects of epoprostenol and iloprost on left ventricular contractility were assessed in vivo and compared to the effects of adenosine and sodium nitroprusside, which exerts vasodilatory properties independently of cAMP.. Prospective, randomized, cross-over in a university laboratory.. Eleven pigs (25.9+/-2.8 kg, balanced anesthesia).. Each animal was exposed to intravenous sodium nitroprusside, adenosine, and epoprostenol in randomized order. Iloprost was administered at the end due to its longer half-life. The dose was titrated to achieve a 25% reduction in diastolic aortic pressure.. Left ventricular contractility was assessed before, during, and after each intervention by determination of the endsystolic elastance with the conductance method. While there was no change in endsystolic elastance upon the infusion of adenosine and sodium nitroprusside; endsystolic elastance increased in the case of epoprostenol (57%) and iloprost (71%).. Left ventricular contractility is increased in vivo by epoprostenol and iloprost but not by adenosine or sodium nitroprusside at equipotent hypotensive dose. A contribution of sympathetic reflex activation of cardiac nerves on the increase in left ventricular contractility cannot be completely ruled out.

Topics: Adenosine; Animals; Antihypertensive Agents; Epoprostenol; Hemodynamics; Hypotension; Iloprost; Myocardial Contraction; Nitroprusside; Random Allocation; Stroke Volume; Swine; Vasodilator Agents; Ventricular Function, Left; Water-Electrolyte Balance

Both aerosolized and intravenous infusion of iloprost caused a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance. Although intravenous infusion caused a large decrease in mean systemic arterial pressure, this was only slightly affected by aerosolized iloprost. Aerosolized iloprost caused a significant decrease in the pulmonary-to-systemic vascular resistance ratio; however, intravenous infusion did not cause a prominent decrease in this ratio.

Topics: Administration, Inhalation; Adolescent; Aerosols; Child; Child, Preschool; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Hypotension; Iloprost; Infant; Infusions, Intravenous; Pulmonary Wedge Pressure; Vascular Resistance; Vasodilator Agents