Cardiopulmonary Dysfunction And Changes In Production Of TXA2 And PGI2 Induced By Intracoronary Injection With Arachidonic Acid

Abstract

A 4 Wedge-Pressure catheter was inserted to 1 cm above aortic valve in ascending aorta through right common carotid artery of 16 rabbits. 1.5 mg/kg of sodium arachidonate (AA) was injected into the proximal portion of ascending aorta after inflation of balloon which obstructed the ascending aorta. Inflation remained for 5 sec, the solution was perfused into coronary arteries. ECG, respiratory movement and blood pressure were recorded. Before, 3 and 60 min after AA, 10 ml of heparinized blood was collected, added with 0.1 ml of Tris-HCl buffer (pH 8.0) containing indomethacin (10 μM in final concentration) and centrifuged to collect PPP for measurement of TXB2 and 6-Keto PGF1α using radio immunoassay. 8 rabbits were injected with 10 mg/kg of (E)-3-[4-(3- pyridylmethyl)phenyl]-2-methyl-2-propenoic acid (OKY-1580, a specific inhibitor on TXA2 synthetase) 3 min before AA injection. In control, arrhythmia and marked ST depression appeared in all cases after AA. Apnea was seen in 4 and 1 case died 7 min after AA. In OKY group, arrhythmia and apnea were not seen. 2 cases showed ST depression. Blood pressure decreased in both the groups similarly. TXB2 values were 1.091+0.498 ng/ml (mean+SD) before, 3.037±0.927 3 min after and 1.014±0.426 60 min after in control. In OKY group those were 1.3154±). 926, 0.830±0.334 and 0.764±0.343. There was a significant difference in the values 3 min after between both the groups. In control, 6-Keto PGF1α values were 3.337± 2.279 ng/ml before, 26.668±16.353 3 min after and 3.975± 3.548 60 min after. In OKY group, those were 2.151±0.528, 61.064±21.420 and 4.264±2.530. There was also a significant difference in the values 3 min after. Histologic findings of heart showed more remarkable ischemic changes in control than in OKY group. These findings suggest that the intracoronary injection with AA induced ischemic changes in heart through TXA2 synthesis at least partially and the changes were able to be prevented by OKY 1580.