Lagente V, Simonetti M P, Fortes Z B, Braquet P
Department of Pharmacology, University of Sao Paulo, Brazil.
Pharmacol Res. 1989 Sep-Oct;21(5):577-85. doi: 10.1016/1043-6618(89)90199-0.
Administration of the local anaesthetic bupivacaine (1.5 or 2 mg/kg, i.v.) to rats elicited a marked decrease of mean arterial blood pressure (MBP) and heart rate (HR) leading to death (in 67% or 90% of animals respectively). Intravenous injection of the specific platelet-activating factor (PAF) antagonist BN 52021 (10 mg/kg), 30 min before bupivacaine administration (2 mg/kg i.v.) suppressed both the decrease of MBP and HR. In contrast, doses of 1 mg/kg BN 52021 given 30 min before or 10 mg/kg administered 5 min before i.v. injection of bupivacaine were ineffective. When BN 52021 (20 mg/kg i.v.) was injected immediately after bupivacaine (2 mg/kg), a partial reversion of the decrease of MBP and HR was observed, whereas the dose of 10 mg/kg was ineffective. A partial recovery of bupivacaine-induced ECG alterations was observed after pretreatment of the rats with BN 52021. Since the administration of BN 52021, at all doses studied, did not alter MBP and HR at the doses used, the bulk of these results clearly demonstrate a protective action of BN 52021, a specific antagonist of PAF, against bupivacaine-induced cardiovascular toxicity. Thus, consistent with its direct effect on heart, PAF appears to be implicated in bupivacaine-induced cardiovascular alterations.
给大鼠静脉注射局部麻醉药布比卡因（1.5或2毫克/千克）会导致平均动脉血压（MBP）和心率（HR）显著下降，最终导致死亡（分别在67%或90%的动物中出现）。在注射布比卡因（2毫克/千克，静脉注射）前30分钟静脉注射特异性血小板活化因子（PAF）拮抗剂BN 52021（10毫克/千克），可抑制MBP和HR的下降。相比之下，在静脉注射布比卡因前30分钟给予1毫克/千克的BN 52021或在注射前5分钟给予10毫克/千克均无效。当在布比卡因（2毫克/千克）后立即静脉注射BN 52021（20毫克/千克）时，可观察到MBP和HR下降的部分逆转，而10毫克/千克的剂量则无效。在用BN 52021预处理大鼠后，观察到布比卡因诱导的心电图改变有部分恢复。由于在所研究的所有剂量下，BN 52021的给药均未改变所用剂量下的MBP和HR，这些结果清楚地表明PAF的特异性拮抗剂BN 52021对布比卡因诱导的心血管毒性具有保护作用。因此，与PAF对心脏的直接作用一致，PAF似乎与布比卡因诱导的心血管改变有关。
