Hoque A N, Hoque N, Hashizume H, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Jpn J Pharmacol. 1995 Mar;67(3):233-41. doi: 10.1254/jjp.67.233.
The effects of dilazep, d-propranolol and lidocaine on the mechanical and metabolic changes induced by lysophosphatidylcholine (LPC) were studied in isolated, perfused working rat heart. After a stabilization period, the heart was perfused for 5 min with LPC (10 microM) alone, LPC plus dilazep (5, 10 or 20 microM), LPC plus d-propranolol (30 or 50 microM) or LPC plus lidocaine (30 or 100 microM) and then perfused with normal Krebs-Henseleit bicarbonate (KHB) buffer for a further 20 min. Perfusion with LPC for 5 min followed by KHB for 20 min irreversibly decreased cardiac mechanical function, decreased the tissue levels of adenosine triphosphate and creatine phosphate significantly, and increased the tissue levels of lactate and free fatty acids including arachidonic acid. Dilazep or d-propranolol significantly attenuated the mechanical and metabolic changes induced by LPC, but lidocaine did not. These results indicate that the exogenous LPC causes ischemia-like changes, suggesting that LPC is one of the important factors in producing ischemia-reperfusion derangements in terms of mechanical and metabolic functions, and that both dilazep and d-propranolol can prevent the LPC-induced myocardial damage.
在离体灌注的大鼠工作心脏中，研究了地拉卓、d-普萘洛尔和利多卡因对溶血磷脂酰胆碱（LPC）诱导的机械和代谢变化的影响。在稳定期后，心脏先单独用LPC（10微摩尔）、LPC加地拉卓（5、10或20微摩尔）、LPC加d-普萘洛尔（30或50微摩尔）或LPC加利多卡因（30或100微摩尔）灌注5分钟，然后再用正常的克雷布斯-亨塞尔特碳酸氢盐（KHB）缓冲液灌注20分钟。用LPC灌注5分钟后再用KHB灌注20分钟，会不可逆地降低心脏机械功能，显著降低三磷酸腺苷和磷酸肌酸的组织水平，并增加乳酸和包括花生四烯酸在内的游离脂肪酸的组织水平。地拉卓或d-普萘洛尔能显著减轻LPC诱导的机械和代谢变化，但利多卡因则不能。这些结果表明，外源性LPC会引起类似缺血的变化，提示LPC在产生缺血-再灌注紊乱的机械和代谢功能方面是重要因素之一，并且地拉卓和d-普萘洛尔都能预防LPC诱导的心肌损伤。
