ozagrel and ataprost

In order to clarify the role of platelets as a factor aggravating cerebral ischemia, an experimental model of ischemia was investigated using thrombocytopenic rats. In addition, the prostacyclin derivative (OP-41483) and the thromboxane A2 synthetase inhibitor (OKY-046), both of which inhibit platelet aggregation, were tested for possible beneficial effects on cerebral ischemia. Cerebral ischemia was produced in spontaneously hypertensive male rats using bilateral common carotid artery ligation (BLCL). Thrombocytopenia was produced with an antiplatelet antiserum which reduced the platelet count to less than 6 x 10(4)/microliters by 24 h. OP-41483 was administered four times hourly (500 ng/kg x 4, i.p.), beginning 1 h prior to BLCL. Similarly, OKY-046 was injected four times hourly (10 mg/kg x 4, i.p.). Brain metabolites such as ATP, lactate and pyruvate and water content were determined after 3 h of cerebral ischemia. Brain levels of ATP in the ischemic rats with thrombocytopenia were higher than those of the ischemic rats without thrombocytopenia. In addition, thrombocytopenia reduced the increase of lactate and water content in the ischemic brain. Animals treated with OP-41483 also maintained higher levels of ATP and lower levels of lactate and water compared to animals given a vehicle. OKY-046 significantly reduced brain water content, but had no effect on the ischemic alteration of brain metabolite levels. These results indicate that platelets play an important role in the progression of metabolic change during ischemia.

Topics: Adenosine Triphosphate; Animals; Blood Platelets; Body Water; Brain; Brain Ischemia; Epoprostenol; Immune Sera; Lactates; Male; Methacrylates; Platelet Aggregation Inhibitors; Platelet Count; Pyruvates; Rats; Rats, Inbred SHR; Reference Values; Thrombocytopenia; Thromboxane-A Synthase

Topics: Acrylates; Adolescent; Adult; Aged; Child; Child, Preschool; Cyclosporins; Epoprostenol; Female; Graft Rejection; Graft Survival; Humans; Kidney; Kidney Transplantation; Male; Methacrylates; Middle Aged; Thromboxane-A Synthase; Ticlopidine

Topics: Acrylates; Chronic Disease; Epoprostenol; Graft Rejection; Humans; Kidney Transplantation; Methacrylates; Thromboxane-A Synthase; Ticlopidine; Time Factors; Vascular Diseases

A full skin thickness burn covering 35 per cent of the total body surface area was inflected on the back of rabbits. The animals were divided into seven groups and the effectiveness of OP-41483, aspirin (ASA), OKY-046 and CV-3988 was studied. All rabbits died between 8 and 24 h after injury in the no therapy group. Renal function tests in this group showed a decrease in Cler and an increase in FENa and CH2O. Such changes were improved slightly with infusion therapy. On the contrary, with OP-41483, OKY-046 and ASA, distinct improvements were observed (in order of extent of improvement), but with CV-3988 the improvements were rather small. As a result these drugs may also be effective in preventing organ failure after burn injury, but as such changes presumably occur immediately after the burn it is considered that a fast-acting agent such as OP-41483 is the most effective form of treatment.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Aspirin; Blood Coagulation; Blood Platelets; Burns; Epoprostenol; Fibrinolysis; Kidney; Methacrylates; Phospholipid Ethers; Platelet Activating Factor; Platelet Aggregation Inhibitors; Rabbits; Thromboxane-A Synthase