iloprost and Brain-Ischemia

The effects of ZK-118.182, a stable analogue of PGD2, were evaluated in an endothelin-1-induced cerebral ischemia rabbit model. Ischemia was induced by endothelin-1 injection (0.25 ng bolus) into subcavian artery and ischemic changes were assessed histologically by the number of ischemic neurons in the brain stem. ZK-118.182 (2 micrograms/kg, bolus into subclavian artery) reduced the number of ischemic neurons when injected 20 min after endothelin-1 injection, Iloprost, a stable analogue of PGI2, was also effective in reducing the number of ischemic neurons in a dose of 0.5 microgram/kg (bolus into subclavian artery). The results suggested that ZK-118.182 has a potent antiischemic effect which is comparable to that of iloprost in rabbits.

Topics: Animals; Brain Ischemia; Dinoprost; Disease Models, Animal; Endothelin-1; Iloprost; Neurons; Platelet Aggregation Inhibitors; Rabbits

Indirect evidence from studies in which calcitonin gene-related peptide was used indicates that anoxic stress suppresses functioning of cerebral vascular ATP-sensitive K+ channels. The purpose of this study was to directly examine effects of total global ischemia on cerebral arteriolar dilator responses to activators of ATP-sensitive K+ channels.. We measured pial arteriolar diameters in anesthetized piglets using a closed cranial window and intravital microscopy. Baseline diameters were approximately 100 microns. Arteriolar responses to aprikalim (10(-8) and 10(-6) mol/L), a pharmacological activator of ATP-sensitive K+ channels, and iloprost (0.1 and 1 microgram/mL), a physiological activator of these channels, were determined before and 1, 2, and 4 hours after a 10-minute period of total global ischemia. Ischemia was caused by increasing intracranial pressure.. Before ischemia, aprikalim dilated cerebral arterioles by 7 +/- 2% at 10(-8) mol/L and by 25 +/- 4% at 10(-6) mol/L (n = 5). At 1 hour after ischemia, aprikalim did not cause significant dilation at either dose (3 +/- 2% at 10(-8) mol/L and 7 +/- 4% at 10(-6) mol/L; P < .05 compared with corresponding preischemic response). Arteriolar dilation returned toward normal values at 2 and 4 hours. Similar results were found with iloprost. Furthermore, prior treatment with indomethacin (5 mg/kg) preserved normal arteriolar dilation to aprikalim and iloprost after ischemia. In contrast, arteriolar dilator responses to prostaglandin E2 were intact after ischemia.. Ischemia transiently eliminates cerebral arteriolar dilation to activation of ATP-sensitive K+ channels; arteriolar responses are suppressed at 1 hour and return toward normal over 2 to 4 hours. In addition, reduced responsiveness can be prevented by prior treatment with indomethacin.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Arterioles; Blood Pressure; Brain; Brain Ischemia; Cerebrovascular Circulation; Dinoprostone; Female; Humans; Iloprost; Infant; Male; Picolines; Potassium Channels; Pyrans; Swine; Vasodilator Agents

This investigation was undertaken to study the effect of iloprost, a stable analogue of prostacyclin, on infarct size after permanent focal cerebral ischemia in the rabbit. Forty-two adult rabbits were subjected to left middle cerebral artery occlusion via the transorbital route. Fourteen rabbits received an intravenous (i.v.) infusion of 30 micrograms/kg iloprost, 7 rabbits received an i.v. infusion of 10 micrograms/ kg, and 9 rabbits received an i.v. infusion of 20 micrograms/kg iloprost. Twelve rabbits received an intravenous infusion of saline. Treatment with iloprost started immediately after middle cerebral artery occlusion and continued for 1 h. After killing the animals, brains were removed and five coronal slices were incubated in a 2,3,5-triphenyltetrazolium chloride solution to determine the infarct size. Treatment with 30 micrograms/kg iloprost significantly reduced the infarct size compared with treatment with saline (3.49 +/- 2.79% vs. 9.03 +/- 4.26%, P < 0.001), but the lower doses of iloprost did not have a beneficial effect on the size of the infarct. These results suggest that intravenous iloprost treatment after occlusion has a highly protective effect without any side effects such as hypotension.

Topics: Animals; Brain; Brain Ischemia; Cerebral Infarction; Hemodynamics; Iloprost; Rabbits; Respiratory Mechanics; Vasodilator Agents