Groban Leanne, Vernon Jason C, Butterworth John
From the Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina.
Anesth Analg. 2004 Apr;98(4):903-909. doi: 10.1213/01.ANE.0000105878.96434.05.
Systemically-administered morphine reduces infarct size in rat models of myocardial ischemia-reperfusion. We sought to determine whether much smaller doses of spinally-administered morphine offer a similar cardioprotective benefit. Barbiturate-anesthetized, open-chested, Wistar rats with chronic indwelling thoracic intrathecal catheters were instrumented for hemodynamic measurements and subjected to 30 min of coronary occlusion and 90 min of reperfusion. Myocardial infarct size was determined using triphenyl-tetrazolium staining. Rats were randomly assigned to receive intrathecal (IT) 0.9% saline (vehicle), IV morphine (0.3 mg/kg) plus IT saline, small-dose IT morphine (0.3 microg/kg), or large-dose IT morphine (3 microg/kg) 20 min before occlusion. IV and both doses of IT morphine reduced infarct size, defined as area of necrosis expressed as a percentage of area at risk (%AN/AAR), as compared with vehicle. The %AN/AAR group means were as follows: IV (n = 7), 30% +/- 6%; IT(small-dose) (n = 9), 30% +/- 5%; IT(large-dose) (n = 9), 18% +/- 4%; and vehicle (n = 10), 47% +/- 5%. There were no significant differences in infarct size among the morphine-pretreated rats. During ischemia-reperfusion, heart rate was unchanged from baseline in the IT(large-dose) group, whereas in the IT(small-dose), IV and vehicle groups, significant declines in heart rate occurred. Changes in arterial blood pressure were similar among groups. These results indicate that IT morphine reduces infarct size in rats, and this benefit is as great as that provided by IV morphine administration.
Our findings suggest that spinally-administered morphine provides a previously unrecognized cardioprotective benefit. In anesthetized rats subjected to ischemia-reperfusion injury, we show that very small doses of intrathecal morphine reduce infarct size in rats, and this benefit is as great as that provided by much larger doses of IV morphine.
全身给药的吗啡可减小大鼠心肌缺血再灌注模型中的梗死面积。我们试图确定小得多剂量的脊髓给药吗啡是否具有类似的心脏保护作用。用巴比妥类药物麻醉、开胸、带有慢性留置胸段鞘内导管的Wistar大鼠用于血流动力学测量，并经历30分钟的冠状动脉闭塞和90分钟的再灌注。使用三苯基四氮唑染色法测定心肌梗死面积。在闭塞前20分钟，将大鼠随机分配接受鞘内注射（IT）0.9%生理盐水（赋形剂）、静脉注射吗啡（0.3mg/kg）加鞘内注射生理盐水、小剂量鞘内注射吗啡（0.3μg/kg）或大剂量鞘内注射吗啡（3μg/kg）。与赋形剂相比，静脉注射和两种剂量的鞘内注射吗啡均减小了梗死面积，梗死面积定义为坏死面积占危险面积的百分比（%AN/AAR）。%AN/AAR组均值如下：静脉注射（n = 7），30%±6%；鞘内注射（小剂量）（n = 9），30%±5%；鞘内注射（大剂量）（n = 9），18%±4%；赋形剂（n = 10），47%±5%。吗啡预处理的大鼠之间梗死面积无显著差异。在缺血再灌注期间，鞘内注射（大剂量）组的心率与基线相比无变化，而在鞘内注射（小剂量）、静脉注射和赋形剂组中，心率出现显著下降。各组动脉血压变化相似。这些结果表明，鞘内注射吗啡可减小大鼠梗死面积，且这种益处与静脉注射吗啡相当。
我们的研究结果表明，脊髓给药的吗啡具有以前未被认识到的心脏保护作用。在经历缺血再灌注损伤的麻醉大鼠中，我们表明非常小剂量的鞘内吗啡可减小大鼠梗死面积，且这种益处与大得多剂量的静脉注射吗啡相当。
