The effect of cyclosporine A dissolved in chremofore or in ethanol and of cortisone on the arterial release of prostacyclin.
Cyclosporine A has been suggested to increase thromboembolic complications after renal transplantation. Therefore, the effect of cyclosporine A (at the clinically used dose of 10 mg/kg) dissolved in either chremofore or ethanol on rabbit vascular prostacyclin release was investigated in an ex vivo perfusion system. The animals received the drugs intravenously either as a single injection the day before operation or daily for 1 month prior to operation. Rabbits given cyclosporine A dissolved in chremofore released less prostacyclin than controls, both after a single injection and after 1 month of daily injections. The vehicle chremofore also gave a significantly lower release of prostacyclin than the control. The response to arachidonic acid with increased release was equal in all groups. Cyclosporine A dissolved in ethanol did not alter the initial release, and ethanol alone did not influence the prostacyclin release. Cortisone depressed the vascular prostacyclin release after daily injections for 1 month, but did not after only one injection. Cyclosporine A dissolved in chremofore and cortisone given in combination did not result in an additive reduction. These findings indicate that the intravenous administration of cyclosporine A dissolved in chremofore, but not that dissolved in ethanol, as well as cortisone, might decrease the vascular defense against thrombus formation. The action of these substances is higher up in the arachidonic acid cascade than the cyclooxygenase level.
Brunkwall
J
J
Department of Surgery and Experimental Research, Lund University, Malmö General Hospital, Sweden.
Bergqvist
D
D
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D003348:Cortisone / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism*; D000431:Ethanol; D005260:Female; D008297:Male; D011092:Polyethylene Glycols; D011817:Rabbits; D012996:Solutions
D012996:Solutions; C022131:cremophor; D000431:Ethanol; D011092:Polyethylene Glycols; D015121:6-Ketoprostaglandin F1 alpha; D016572:Cyclosporine; D003404:Creatinine; D011464:Epoprostenol; D003348:Cortisone