Oeltgen Peter R, Govindaswami Meera, Witzke Donald B
Department of Pathology and Laboratory Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Acad Emerg Med. 2006 Feb;13(2):127-33. doi: 10.1197/j.aem.2005.08.012.
Delta opioids have been shown to confer ischemic preconditioning and pharmacologic ischemic preconditioning to the myocardium. However, their role in providing extended pharmacologic ischemic preconditioning in hemorrhagic shock has not been explored. The authors examined the effects of 24-hour preinfusions of a selective delta opioid receptor agonist, Deltorphin-Dvariant (Delt-Dvar), on hemodynamic stability and duration of survival in a rat model of severe hemorrhagic shock.
Conscious Sprague-Dawley rats with indwelling catheters were hemorrhaged at a rate of 3.18 mL/l00 g over 20 minutes. Twenty-four hours before hemorrhage, the control group (n = 14) was infused with 1.0 mL lactated Ringer's solution, and the Delt-Dvar-treated group (n = 22) was infused with 5.0 mg/kg Delt-Dvar in 1.0 mL lactated Ringer's solution. Rats were continuously monitored for heart rate (HR), mean arterial pressure, and four-hour survival rates. Plasma lactate levels were determined at the beginning of hemorrhage and the end of hemorrhage.
At 240 minutes, only one of 14 controls (7.1%) survived, while 16 (72.7%) of the 22 experimental rats survived. No significant differences in heart rate between controls and Delt-Dvar-treated rats were noted. Increases in mean arterial pressure of Delt-Dvar-treated rats at the beginning of hemorrhage and at the end of hemorrhage were found to be significant (p < 0.05). At 240 minutes, heart rate and mean arterial pressure were not different between the single surviving control and the Delt-Dvar group. At the end of hemorrhage, lactate levels in the Delt-Dvar-treated group were 8.5 (+/- 0.5) mmol/L versus 10.8 (+/- 0.6) mmol/L (p < 0.05) in the control group.
Twenty-four-hour pretreatment with Delt-Dvar decreases plasma lactate levels and improves hemodynamic stability and survival during hemorrhagic shock. The use of delta-specific opioids may improve survival from hemorrhagic shock and have clinical utility in providing ischemic protection in scenarios of planned ischemia.
已证明δ阿片类药物可赋予心肌缺血预处理和药理学缺血预处理作用。然而，其在出血性休克中提供延长的药理学缺血预处理方面的作用尚未得到探索。作者研究了选择性δ阿片受体激动剂Deltorphin-D变体（Delt-Dvar）24小时预输注对严重出血性休克大鼠模型血流动力学稳定性和存活时间的影响。
对留置导管的清醒斯普拉格-道利大鼠，在20分钟内以3.18 mL/100 g的速率进行出血。在出血前24小时，对照组（n = 14）输注1.0 mL乳酸林格氏液，Delt-Dvar治疗组（n = 22）输注含5.0 mg/kg Delt-Dvar的1.0 mL乳酸林格氏液。持续监测大鼠的心率（HR）、平均动脉压和4小时存活率。在出血开始时和出血结束时测定血浆乳酸水平。
在240分钟时，14只对照组大鼠中只有1只（7.1%）存活，而22只实验大鼠中有16只（72.7%）存活。对照组和Delt-Dvar治疗组大鼠的心率无显著差异。发现Delt-Dvar治疗组大鼠在出血开始时和出血结束时的平均动脉压升高显著（p < 0.05）。在240分钟时，唯一存活的对照组大鼠和Delt-Dvar组之间的心率和平均动脉压无差异。在出血结束时，Delt-Dvar治疗组的乳酸水平为8.5（±0.5）mmol/L，而对照组为10.8（±0.6）mmol/L（p < 0.05）。
Delt-Dvar 24小时预处理可降低出血性休克期间的血浆乳酸水平，改善血流动力学稳定性和存活率。使用δ特异性阿片类药物可能提高出血性休克的存活率，并在计划缺血情况下提供缺血保护方面具有临床应用价值。
