Smith E F, Egan J W, Bugelski P J, Hillegass L M, Hill D E, Griswold D E
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania 19406.
Am J Physiol. 1988 Nov;255(5 Pt 2):H1060-8. doi: 10.1152/ajpheart.1988.255.5.H1060.
Infiltration of polymorphonuclear leukocytes (PMN) is associated with the progression of myocardial infarction and reperfusion injury. However, little is known about the time course of cellular infiltration. To investigate this issue, rats were subjected to 30 min of coronary artery occlusion followed by reperfusion for less than or equal to 96 h. Myocardial injury was determined by measuring the depletion of myocardial creatine phosphokinase activity, and PMN infiltration was assessed by measuring myeloperoxidase (MPO) activity. MPO activity increased from 0.7 U/g tissue in non-operated animals, to a peak of 6.7 +/- 0.8 and 6.4 +/- 1.4 U/g at 6 and 24 h after coronary artery reperfusion, respectively. MPO activity decreased to 3.3 +/- 0.8 U/g at 48 h and 1.1 +/- 0.4 U/g at 96 h, suggesting diminished PMN accumulation. Histological examination confirmed the accumulation and resolution of PMN over the 96-h period. At 24 h, there was a significant linear correlation between infarct size and MPO activity, whereas at 96 h no relationship was found. These data indicate that PMN infiltration occurs early in response to reperfusion injury and persists for only 24 h after initiation of reperfusion. These findings suggest that attempts to moderate inflammatory cell responses to myocardial injury should be administered early after coronary artery reperfusion to limit the accumulation of potentially deleterious inflammatory cells.
多形核白细胞(PMN)浸润与心肌梗死及再灌注损伤的进展相关。然而,关于细胞浸润的时间进程却知之甚少。为研究此问题,对大鼠进行30分钟冠状动脉闭塞,随后再灌注小于或等于96小时。通过测量心肌肌酸磷酸激酶活性的消耗来确定心肌损伤,通过测量髓过氧化物酶(MPO)活性来评估PMN浸润。MPO活性从未手术动物的0.7 U/g组织,分别在冠状动脉再灌注后6小时和24小时增加到峰值6.7±0.8和6.4±1.4 U/g。MPO活性在48小时降至3.3±0.8 U/g,在96小时降至1.1±0.4 U/g,提示PMN积累减少。组织学检查证实了96小时内PMN的积累和消退。在24小时时,梗死面积与MPO活性之间存在显著的线性相关性,而在96小时时未发现相关性。这些数据表明,PMN浸润在再灌注损伤后早期发生,且在再灌注开始后仅持续24小时。这些发现提示,为减轻炎症细胞对心肌损伤的反应,应在冠状动脉再灌注后尽早进行干预,以限制潜在有害炎症细胞的积累。