ataprost and Ischemia

Topics: Animals; Antioxidants; Bilirubin; Epoprostenol; Graft Survival; Hepatectomy; Hypertonic Solutions; Ischemia; Liver Transplantation; Organ Preservation; Organ Preservation Solutions; Platelet Aggregation Inhibitors; Reperfusion Injury; Superoxides; Swine; Thiazoles; Time Factors; Tissue and Organ Harvesting

Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drug-related side effects. This study investigated whether misoprostol, prostaglandin E1 analogue, and OP-41483, prostaglandin I2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage.. Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 microg/kg/min) and for 3 hours after reperfusion (0.5 microg/kg/min). Animals were divided into five groups: untreated control group (n=10); high-dose misoprostol (total 100 microg/kg) group (MP-H, n=5); middle-dose misoprostol (50 microg/kg) group (MP-M, n=5); low-dose misoprostol (25 microg/kg) group (MP-L, n=5); and OP-41483 group (OP, n=5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed.. Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBF, and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP-M, MP-L, and OP animals experienced only transient hypotension.. These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects.

Topics: Analysis of Variance; Animals; Dogs; Dose-Response Relationship, Drug; Epoprostenol; Female; Ischemia; Liver; Liver Function Tests; Misoprostol; Platelet Aggregation Inhibitors; Prostaglandins, Synthetic; Reperfusion Injury

Topics: Animals; Epoprostenol; Graft Survival; Ischemia; Liver; Liver Transplantation; Organ Preservation; Prostaglandins, Synthetic; Swine; Thrombomodulin; Transplantation, Homologous

The purpose of this study was to estimate the effect of OP-41483 (Prostaglandin I2 analog) on normothermic liver ischemia by measuring the systemic and hepatic hemodynamics, oxygen metabolism, hematological and biochemical data. Sixty minutes of normothermic ischemia was induced by cross-clamping the hepatic artery and the portal vein with the bypass. The animals, weighing 10 to 15 kg, were divided into three groups: animals (n = 7) given no drugs (group I), those (n = 7) given OP-41483 (0.4 microgram/kg/min) for 30 minutes prior to the initiation of ischemia and after the beginning of reperfusion (group II), and those (n = 7) given OP-41483 (0.4 microgram/kg/min) for 30 minutes before ischemia and 3 hours after reperfusion (group III). The total hepatic blood flow was significantly higher 30 minutes after reperfusion in groups II and III than in group I (p < 0.05). The oxygen delivery to the liver and oxygen consumption in the liver decreased after reperfusion in group I, but there were no significant differences in these values before and after hepatic ischemia in groups II and III. The hepatic tissue blood flow was significantly higher in groups II and III than in group I after reperfusion. In group III, oxygen consumption in the liver was significantly higher 2 to 3 hours after reperfusion than in groups I and II. The systemic oxygen consumption after reperfusion recovered more rapidly in groups II and III than in group I. These results indicate that OP-41483 has a beneficial effect on the recovery of the hepatic microcirculation affected by ischemia.

Topics: Animals; Dogs; Epoprostenol; Hemodynamics; Ischemia; Liver; Liver Circulation; Oxygen; Oxygen Consumption

To estimate the effects of the prostacyclin analog (OP-41483) on normothermic liver ischemia and reperfusion injury, saline (Group 1, N = 8), heparin (group 2, N = 8, 100 u/kg) or OP-41483 (group 3, N = 8, 400 ng/kg/min) was infused intravenously for 30 min before and after liver ischemia in rats. There were no significant differences in survival, or transaminase at 30 min after reperfusion among the three groups. Hepatic vessel flow and tissue flow were measured for the first 30 min after reperfusion. Hepatic tissue flow increased for the first 30 min after reperfusion in the group 3 rats, but not in the groups 2 and 3 rats. There were significant differences in hepatic tissue flow between the groups 1 and 3 rats at 20 min (p < 0.05), as well as significant differences between the groups 1 and 3 rats (p < 0.01) and the groups 1 and 2 rats (p < 0.05) at 30 min after reperfusion. There were no significant differences in total hepatic inflow among the three groups. Our data suggest that OP-41483 exerts beneficial effects by improving the microcirculation and increasing the effective hepatic blood flow in the ischemically injured liver after reperfusion.

Topics: Animals; Epoprostenol; Female; Ischemia; Liver; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Regional Blood Flow; Reperfusion Injury; Survival Rate

The effects of TCV-309, a specific platelet-activating factor (PAF) antagonist, and OP-41483, a prostaglandin I2 analogue, on warm ischemia/reperfusion injury of the rat liver were studied. Rats were divided into five groups by the duration of warm ischemia and the treatment used. The NS1 group (normal saline pretreatment) had 60 min of warm ischemia, while the NS2 group (normal saline pretreatment), the PGI2 group (OP-41483, 500 ng/kg/min pretreatment), the TCV group (TCV-309, 3 micrograms/kg), and the PGI2+TCV group (both the above dosages) underwent 120 min of warm ischemia. Postoperative survival after 30 days, bile secretion, serum endotoxin levels, and tissue glutathione levels after 60 min of reperfusion were compared between the groups. The survival rates for the NS1, NS2, PGI2, TCV, and PGI2+TCV groups were 80%, 0%, 50%, 80%, and 86.7%, respectively. Bile secretion, which has a strong correlationship with hepatic cellular ATP level, was strongly correlated with survival. The NS2 group had a high serum endotoxin level--however, the PGI2 and PGI2+TCV groups had normal levels. Although there were some discrepancies between survival and the tissue glutathione level, combined treatment with the PGI2 analogue and TCV-309 was most effective in inhibited oxidative stress. In conclusion, TCV-309 increased the survival rate after 120 min of warm hepatic ischemia without endotoxemia by the PGI2 analogue. This finding suggest that warm ischemia/reperfusion injury is related to the generation of PAF. Combined pretreatment with TCV-309 and a PGI2 analogue may be useful in liver transplantation.

Topics: Animals; Bile; Endotoxins; Epoprostenol; Glutathione; Ischemia; Isoquinolines; Liver; Male; Platelet Activating Factor; Pyridinium Compounds; Rats; Rats, Wistar; Reperfusion Injury; Tetrahydroisoquinolines

The purpose of this study is to evaluate the effect of PGI2 analogue on the warm ischemic injury in the reimplantation model of the lung. Twenty-five mongrel dogs were subjected to this experiment in which the left thoracotomy and complete left hilar stripping were performed. The dogs were divided into 4 groups. The control group (8 dogs) did not have any medical treatment. I2 1 microgram group (7 dogs) received PGI2 analogue in the amount of 1 microgram/kg/min for 30 min during hilar dissection. I2 50 ng group (5 dogs) received PGI2 analogue in the amount of 50 ng/kg/min for 30 minutes. Heparin group (5 dogs) received 100 U/kg of heparin after hilar stripping. Then left, PA, PV, and Bronchus were clamped for 1 hour to make the left lung a warm ischemic state. To evaluate the function of the left lung subjected for a warm ischemia, right pulmonary artery was occluded for 10 minutes and PaO2, PaCO2, Qs/Qt, pulmonary artery pressure, pulmonary vascular resistance, thromboxane B2, and 6-keto-PGF1 alpha were measured. Two hours after reperfusion, pulmonary microangiography and histological investigation were performed. As a result of warm ischemia, PaO2 was 158 mmHg with 70% FiO2 1 hour after reperfusion in control group, whereas it was maintained at as high as 299 mmHg in I2 1 microgram group. PaCO2, Qs/Qt, pulmonary artery pressure, as well as the pulmonary vascular resistance were almost normal throughout the experiment in I2 1 microgram group, but they gradually elevated in control group during the experiments. In the other two groups these parameter are not so satisfactory as in I2 1 microgram group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Dogs; Epoprostenol; Ischemia; Lung; Lung Transplantation; Pulmonary Circulation; Temperature

The effect of OP-41483, a stable prostacyclin (PGI2) analog, on ischemic acute renal failure (ARF) was investigated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creatinine levels remained relatively low during postoperative days 1-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histologic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed extensive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical setting.

Topics: Acute Kidney Injury; Animals; Creatinine; Dogs; Epoprostenol; Female; Ischemia; Kidney; Male; Renal Circulation

The effect of a new prostacyclin analogue OP-41483 on ischemic colonic anastomosis was investigated in dogs. Colonic ischemia was produced by devascularization of the marginal vessels in the left colon and graded into three degrees by measuring colonic blood flow with a hydrogen gas clearance method. The agent was administered intravenously after devascularization using a continuous infusion pump. The parameters studied were colonic blood flow in the submucosal layer, rate of anastomotic leakage, beta-glucuronidase activity and protein content of the colonic mucosa, and histologic changes. After administration of the agent, blood flow increased significantly and beta-glucuronidase activity at the anastomotic site was well preserved at a relatively high level in spite of ischemic change. The anastomotic leakage rate was significantly decreased. The present study proved that administration of this new prostacyclin analogue minimizes ischemic damage, and may be of considerable importance in ischemic colonic anastomoses.

Topics: Anastomosis, Surgical; Animals; Colon; Dogs; Epoprostenol; Female; Glucuronidase; Ischemia; Male; Microcirculation; Platelet Aggregation Inhibitors; Proteins; Regional Blood Flow; Surgical Wound Dehiscence

Topics: Animals; Epoprostenol; Ischemia; Kidney; Prostaglandins, Synthetic; Rabbits; Renal Artery