op-41483-alpha-cyclodextrin and Ischemia

To quantify the morphologic protection of PGE1 on renal glomerulus following normothermic acute renal ischemia.. This experimental study was carried out in 48 adult male Wistar rats. A simple right nephrectomy was performed in all rats. The rats were divided into two groups: one group was perfused with PGE1 and the other group with saline solution immediately after acute renal ischemia, which was produced by non-traumatic vascular clamping. The ischemia times were 15 and 60 minutes. The recovery period ranged from 24 hours to 7 days. After this period the animals were anesthetized and sacrificed. Histological and morphometric analyses of the right kidneys of the control group and the left kidneys of the study group were performed.. The mortality was 31% (18.5% for the group perfused with PGE1 and 11.4% for the group perfused with saline solution). Kidneys of rats perfused with saline solution weighed more than the kidneys of rats perfused with PGE1 (1.771 +/- 0.455 and 1.55 +/- 0.34, respectively). Acute tubular necrosis was observed after 60 minutes' ischemia and was more evident in the saline than in the PGE1 group. The morphometric study showed no significant differences between the control (normal) and the PGE1 group for glomerular diameter (p < or = 0.101), sphericity factor (p < or = 0.239), glomerular perimeter (p < or = 0.092) and glomerular volume (p < or = 0.059). However, significant differences were found between the control and the saline perfusion group for area (p < or = 0.000), diameter (p < or = 0.000), perimeter (p < or = 0.000) and volume (p < or = 0.000).. Kidney weight after ischemia increased more in the saline than in the PGE1-treated group since the edema in the renal parenchyma is attenuated by the anti-inflammatory and cytoprotective effects of PGE1. The morphometric study showed that in comparison to saline, PGE1 exerts a cytoprotective effect, although it is not considerable.

Topics: Acute Disease; alpha-Cyclodextrins; Alprostadil; Animals; Cyclodextrins; Epoprostenol; Ischemia; Kidney; Kidney Glomerulus; Male; Rats; Rats, Wistar

The purpose of the experimental study was to investigate the beneficial effects of aPGI2 analogue (OP-41483-alpha-CD; aPGI2) on hepatic dysfunction after warm ischemia and reperfusion. Hepatic warm ischemia was produced by temporary clamping of the portal vein and hepatic artery. Experimental groups were divided into three groups: Group I; 60-minutes ischemia, Group II; 90-minutes ischemia, Group III; 90-minutes ischemia with intravenous aPGI2 (0.25 microgram/kg/min) infusion. The results were as follows: 1; In groups I and III, hepatic tissue flow showed a marked increase after reperfusion when compared to Group II. 2; Arterial ketone body ratio in Groups I and III recovered significantly faster than those of Group II. 3; The tissue total adenine-nucleotide levels in Groups I and III were significantly higher than those of Group II. 4; In the comparison of the radical intensity which was measured by ESR spectroscopy, the free radical of the hepatic venous blood was markedly generalized after reperfusion in Group II. However, production of free radical has significantly suppressed in Group III when compared to Group II. These results suggest that aPGI2-treatment might improved the ischemic damaged liver and might improve the prognosis of the transplanted patient.

Topics: Alanine Transaminase; alpha-Cyclodextrins; Animals; Aspartate Aminotransferases; Cyclodextrins; Dogs; Epoprostenol; Fibrinolytic Agents; Ischemia; Liver Diseases; Reperfusion Injury

The effect of a chemically stable prostacyclin analog, OP-41483 alpha-cyclodextrin clathrate (OP-41483.alpha-CD), on vascular lesions, platelet aggregation and blood pressure were examined and compared with those of prostaglandin E1 alpha-cyclodextrin clathrate (PGE1.CD) in in vivo rat models. 1) In the laurate (1 mg/leg, i.a.)-induced arterial thrombotic model, OP-41483.alpha-CD (1 microgram/kg/min, i.v.) prevented the progression of femoral arterial vascular lesions and enhanced the development of collaterals in the femoral artery. PGE1.CD did not inhibit the progression of vascular damages. 2) In the model of vasoconstriction induced by epinephrine (0.05 mg/tail, s.c.) and ergotamine (2 mg/kg, s.c.), OP-41483.alpha-CD and PGE1.CD, at 1 microgram/kg/min, inhibited the progress of of tail gangrene and lessened the decrease in tail cutaneous blood flow. 3) OP-41483.alpha-CD (1 microgram/kg/min) suppressed the ADP (0.1 mg/kg/min, i.v.)-induced decrease in the number of circulating platelets without affecting the change in blood pressure. In contrast, PGE1.CD (3 micrograms/kg/min) inhibited ADP-induced thrombocytopenia with a decrease in blood pressure. These results indicate that OP-41483.alpha-CD has antiplatelet and cutaneous blood flow improving activities that are greater than its hypotensive effect and may be of therapeutic potential in peripheral vascular diseases.

Topics: alpha-Cyclodextrins; Alprostadil; Analysis of Variance; Animals; Blood Pressure; Cyclodextrins; Epinephrine; Epoprostenol; Ergotamine; Femoral Artery; Ischemia; Laurates; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Rats, Inbred Strains; Thrombosis; Vasoconstriction