Maulik N, Engelman R M, Wei Z, Liu X, Rousou J A, Flack J E, Deaton D W, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington 06030-1110, USA.
Circulation. 1995 Nov 1;92(9 Suppl):II381-8. doi: 10.1161/01.cir.92.9.381.
Heat-stress preconditioning of mammalian heart has been found to confer protection against ischemic reperfusion injury. Heat shock is generally provided by warming the animal by mechanical means, which is often impractical in a clinical setting. Amphetamine, a sympathomimetic drug, can elevate the body temperature as a result of enhanced endogenous lipolysis. In this study, we examined the effects of heat shock induced by amphetamine on postischemic myocardial recovery in a setting of coronary revascularization for acute myocardial infarction.
Adult Yorkshire swine were injected with amphetamine (3 mg/kg IM) (n = 12), and body temperature was continuously monitored. For control studies, the pigs were injected with saline (n = 12). Five swine in each group were killed after 3 hours to obtain biopsies of vital organs to measure heat-shock protein (HSP) mRNAs. After 40 hours, the remaining 7 pigs in each group were placed on cardiopulmonary bypass, and the isolated, in situ heart preparations were subjected to 1 hour of occlusion of the left anterior descending coronary artery followed by 1 hour of global hypothermic cardioplegic arrest and 1 hour of reperfusion. Postischemic myocardial performance was monitored by measuring left ventricular (LV) pressure, its dP/dt, myocardial segment shortening, and coronary blood flow. Cellular injury was examined by measurement of creatine kinase release. The antioxidant enzymes superoxide dismutase and catalase were also assayed. Amphetamine treatment was associated with the induction of mRNAs for HSP 27, HSP 70, and HSP 89 in all the vital organs, including heart, lung, liver, kidney, and brain. Amphetamine also enhanced superoxide dismutase and catalase activities in the heart. Significantly greater recovery of LV contractile functions was noticed, as demonstrated by improved recovery of LV developed pressure (61% versus 52%), LV dP/dtmax (52% versus 44%), and segment shortening (46.2% versus 10%) and reduced creatine kinase release in the amphetamine group.
The results demonstrate that amphetamine can induce whole-body heat shock that can precondition the heart, enhancing cellular tolerance to ischemia-reperfusion injury. Amphetamine is a sympathomimetic drug that may be used for preconditioning.
已发现对哺乳动物心脏进行热应激预处理可使其免受缺血再灌注损伤。热休克通常通过机械方式使动物升温来实现，这在临床环境中往往不切实际。苯丙胺是一种拟交感神经药物，可因内源性脂肪分解增强而使体温升高。在本研究中，我们在急性心肌梗死冠状动脉血运重建的背景下，研究了苯丙胺诱导的热休克对缺血后心肌恢复的影响。
给成年约克夏猪注射苯丙胺（3mg/kg，肌肉注射）（n = 12），并持续监测体温。作为对照研究，给猪注射生理盐水（n = 12）。每组5头猪在3小时后处死，获取重要器官活检组织以测量热休克蛋白（HSP）mRNA。40小时后，每组剩余的7头猪进行体外循环，对离体原位心脏标本进行1小时左前降支冠状动脉闭塞，随后1小时全身低温心脏停搏和1小时再灌注。通过测量左心室（LV）压力、其dP/dt、心肌节段缩短和冠状动脉血流来监测缺血后心肌功能。通过测量肌酸激酶释放来检查细胞损伤。还测定了抗氧化酶超氧化物歧化酶和过氧化氢酶。苯丙胺治疗与包括心脏、肺、肝、肾和脑在内的所有重要器官中HSP 27、HSP 70和HSP 89的mRNA诱导有关。苯丙胺还增强了心脏中超氧化物歧化酶和过氧化氢酶的活性。苯丙胺组的左心室收缩功能恢复明显更好，表现为左心室舒张末压恢复改善（61%对52%）、左心室dP/dtmax恢复改善（52%对44%）、节段缩短恢复改善（46.2%对10%）以及肌酸激酶释放减少。
结果表明，苯丙胺可诱导全身热休克，从而对心脏进行预处理，增强细胞对缺血再灌注损伤的耐受性。苯丙胺是一种拟交感神经药物，可用于预处理。
