Engler R, Covell J W
Circ Res. 1987 Jul;61(1):20-8. doi: 10.1161/01.res.61.1.20.
Regional ventricular dysfunction (the stunned myocardium) persists for several hours after 15 minutes of ischemia and reperfusion in the dog. Superoxide-radical-induced damage appears to be one of the mechanisms of this injury. We tested whether granulocytes were a direct source of injury in the stunned myocardium in the 15-minute ischemia dog model. Regional function during agranulocytic extracorporeal coronary perfusion (using Leukopak filters) with ischemia and reperfusion was compared with function during a second period of ischemia and reperfusion after removal of the filters (granulocytopenia). Flow reduction and reperfusion flow, preload, afterload, and inotropic stimulation were the same during agranulocytic and granulocytopenic perfusion. During agranulocytic perfusion, stunning did not occur (greater than 100% of preischemic function during reperfusion), but when the filters were removed and about 10% of the normal granulocyte count was present, stunning occurred with only 76% return of function at 60 minutes of reperfusion (p less than 0.01). A second series of studied animals with extracorporeal perfusion and granulocyte replete perfusion all had less than 75% return of regional function, indicating that the agranulocytic perfusion and not the extracorporeal aspects of the experiment prevented stunning. We conclude that granulocytes are the direct source of the injury in stunned myocardium and apparently the main source of superoxide in the 15-minute ischemia dog model. Other possible granulocyte-related mechanisms of reperfusion injury include capillary no-reflow, causing microvascular ischemia and degranulation leading to enzyme-induced damage.
在犬类动物中,局部心室功能障碍(心肌顿抑)在缺血15分钟并再灌注后会持续数小时。超氧阴离子自由基诱导的损伤似乎是这种损伤的机制之一。我们测试了在15分钟缺血犬模型中,粒细胞是否是心肌顿抑时损伤的直接来源。将使用白细胞过滤器进行无粒细胞体外冠状动脉灌注并缺血再灌注期间的局部功能,与去除过滤器后(粒细胞减少)第二次缺血再灌注期间的功能进行比较。无粒细胞灌注和粒细胞减少灌注期间的血流减少、再灌注血流、前负荷、后负荷和变力刺激相同。在无粒细胞灌注期间,未发生心肌顿抑(再灌注期间大于缺血前功能的100%),但当去除过滤器且存在约10%的正常粒细胞计数时,再灌注60分钟时出现心肌顿抑,功能仅恢复76%(p<0.01)。第二组进行体外灌注和粒细胞充足灌注的研究动物,局部功能恢复均小于75%,这表明无粒细胞灌注而非实验的体外方面可预防心肌顿抑。我们得出结论,在心肌顿抑中,粒细胞是损伤的直接来源,并且在15分钟缺血犬模型中显然是超氧阴离子的主要来源。再灌注损伤其他可能的与粒细胞相关的机制包括毛细血管无复流,导致微血管缺血,以及脱颗粒导致酶诱导的损伤。