预先给予 δ-阿片受体激动剂对布比卡因致大鼠心肌毒性的影响。

Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats.

机构信息

Department of Anesthesia, Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China.

Division of Epidemiology, Biostatistics and Environmental Health, Scholl of Health, University of Memphis, Memphis, USA.

出版信息

BMC Anesthesiol. 2022 Jan 12;22(1):19. doi: 10.1186/s12871-022-01568-x.

DOI:10.1186/s12871-022-01568-x

PMID:35021986

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8753886/

Abstract

BACKGROUND

Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics.

METHODS

Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg·min normal saline, group LE received 2 ml·kg·min 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg·min until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated.

RESULTS

All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4-20.7] versus 7.2 [5.9-8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0-29.1] versus 11.3 [10.7-13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9-11.7] versus 5.6 [4.5-7.0], p = 0.060).

CONCLUSIONS

Our data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.

摘要

背景

δ-阿片受体广泛表达于人和啮齿动物的心脏中，已被证明可保护心肌免受缺血/再灌注和心力衰竭的损伤。δ-阿片受体拮抗剂可阻断脂肪乳剂对局部麻醉药心脏毒性的挽救作用。然而，尚无证据表明 δ-阿片受体激动剂直接影响局部麻醉药的心脏毒性。

方法

麻醉的 Sprague Dawley 大鼠分为五组。NS 组给予 2 ml·kg·min 生理盐水，LE 组给予 2 ml·kg·min 30%脂肪乳，BW 组给予 0.1、1.0 或 5.0 mg/kg BW373U86（一种 δ-阿片受体激动剂），持续 5 min。然后以 3.0 mg·kg·min 的速度静脉输注 0.5%布比卡因，直至心搏停止。记录心律失常、50%平均动脉压降低、50%心率降低和心搏停止的时间，并计算每个时间点的布比卡因剂量。

结果

与 NS 组相比，BW373U86 的三种不同剂量均未影响心律失常、50%平均动脉压降低、50%心率降低和布比卡因心搏停止剂量。30%的 LE 显著增加了布比卡因引起 50%平均动脉压降低的阈值（17.9 [15.4-20.7] 与 7.2 [5.9-8.7]，p=0.018）、50%心率降低（18.7±4.2 与 8.8±1.7，p<0.001）和心搏停止（26.5 [21.0-29.1] 与 11.3 [10.7-13.4]，p=0.008）。与 NS 组相比，LE 组和 NS 组在布比卡因引起心律失常的剂量上无差异（9.9 [8.9-11.7] 与 5.6 [4.5-7.0]，p=0.060）。