Greenfield D T, Greenfield L J, Hess M L
Department of Medicine (Division of Cardiology), Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J Thorac Cardiovasc Surg. 1988 May;95(5):799-813.
Oxygen-derived free radicals and intracellular calcium overload have been implicated as mediators of myocardial ischemia/reperfusion injury. We hypothesized that free radical scavengers or calcium channel blockers could enhance the protection afforded the isolated, working rat heart by crystalloid cardioplegia against this type of injury at 37 degrees C. Hearts from 42 male rats in seven groups (n = 6) were studied in an isolated, working heart preparation measuring aortic flow (ml/min/gm dry wt), peak systolic pressure (mm Hg), coronary artery flow (ml/min/gm dry wt), and calculated coronary vascular resistance (dyne.sec.cm-5/gm dry wt). Creatine kinase and lactate dehydrogenase release were measured before ischemia and at various times during the postischemic reperfusion period. Time-matched control hearts (group 1) were perfused for 2 hours. After finding that 30 minutes of ischemia and 10 minutes of reperfusion (group 2) produced significant (p less than 0.01) functional impairment that was completely protected (group 3) by a preischemic bolus of St. Thomas' Hospital cardioplegic solution, we again found significant (p less than 0.01) functional impairment after 40 minutes of ischemia and 10 minutes (group 4) or 20 minutes (group 5) of reperfusion despite a preischemic bolus of St. Thomas' Hospital cardioplegic solution. Diltiazem (10 mg/L) plus St. Thomas' Hospital cardioplegic solution (group 6) did not significantly (p less than 0.01) enhance functional recovery. Addition of superoxide dismutase plus catalase (200 microns/ml) (group 7) produced marked improvement in functional recovery that did not differ significantly (p less than 0.01) from control results (group 1). The creatine kinase and lactate dehydrogenase data strongly supported the preceding functional data. Coronary flow and vascular resistance were not significantly (p less than 0.01) changed from control values in any group. We conclude that the addition of superoxide dismutase and catalase but not diltiazem to St. Thomas' Hospital cardioplegic solution can significantly enhance myocardial protection against normothermic ischemia/reperfusion injury. This implicates oxygen-derived free radicals as mediators of this type of injury.
氧衍生自由基和细胞内钙超载被认为是心肌缺血/再灌注损伤的介质。我们假设自由基清除剂或钙通道阻滞剂可以增强晶体心脏停搏液对37℃下离体工作大鼠心脏这种类型损伤的保护作用。对七组（n = 6）共42只雄性大鼠的心脏进行研究，采用离体工作心脏制备方法，测量主动脉流量（ml/分钟/克干重）、收缩压峰值（mmHg）、冠状动脉流量（ml/分钟/克干重），并计算冠状动脉血管阻力（达因·秒·厘米⁻⁵/克干重）。在缺血前以及缺血后再灌注期的不同时间测量肌酸激酶和乳酸脱氢酶的释放。时间匹配的对照心脏（第1组）灌注2小时。在发现30分钟缺血和10分钟再灌注（第2组）产生显著（p < 0.01）的功能损害，而缺血前推注圣托马斯医院心脏停搏液可完全保护（第3组）后，我们再次发现，尽管有缺血前推注圣托马斯医院心脏停搏液，40分钟缺血和10分钟（第4组）或20分钟（第5组）再灌注后仍有显著（p < 0.01）的功能损害。地尔硫䓬（10mg/L）加圣托马斯医院心脏停搏液（第6组）并未显著（p < 0.01）增强功能恢复。添加超氧化物歧化酶加过氧化氢酶（200微克/毫升）（第7组）使功能恢复有显著改善，与对照结果（第1组）相比无显著差异（p < 0.01）。肌酸激酶和乳酸脱氢酶数据有力地支持了上述功能数据。任何组的冠状动脉流量和血管阻力与对照值相比均无显著（p < 0.01）变化。我们得出结论，在圣托马斯医院心脏停搏液中添加超氧化物歧化酶和过氧化氢酶而非地尔硫䓬可显著增强对常温缺血/再灌注损伤的心肌保护作用。这表明氧衍生自由基是这种类型损伤的介质。
