Kern Karl B, Berg Robert A, Hilwig Ronald W, Larson Douglas F, Gaballa Mohamed A
Sarver Heart Center, University of Arizona College of Medicine, 1501 N. Campbell, Tucson, AZ 85724, USA.
Resuscitation. 2008 Jun;77(3):401-9. doi: 10.1016/j.resuscitation.2008.01.026. Epub 2008 Mar 21.
Increases in serum cytokines have been reported after successful resuscitation from prolonged ventricular fibrillation (VF). Pro-inflammatory cytokines can stimulate inducible nitric oxide synthase (iNOS) to produce excessive levels of nitric oxide (NO). High levels of both myocardial inflammatory cytokines and nitric oxide levels can depress myocardial contractile function. We hypothesized that myocardial pro-inflammatory cytokines and iNOS activity would increase following successful resuscitation from prolonged ventricular fibrillation cardiac arrest, and that such increases would parallel the development of post-resuscitation myocardial dysfunction.
Ventricular fibrillation cardiac arrest was induced in seven domestic swine (25+/-5 kg). After 10 min of untreated VF, the animals were defibrillated and resuscitated. Left ventricular (LV) systolic and diastolic function measurements, serum samples (arterial and coronary sinus) for IL-8 cytokine quantification, and LV myocardial biopsies were collected before, during, and after resuscitation. Quantification of myocardial endothelial (eNOS) and inducible (iNOS) nitric oxide synthase protein levels were determined using immunoblot analyses and protein localization was examined using immunohistochemistry.
Post-resuscitation LV systolic and diastolic functions were depressed while increases in both coronary sinus IL-8 levels and myocardial iNOS activity were found. Compared to pre-arrest baseline, levels of iNOS protein increased during VF (p < or = 0.05) and continued to increase throughout the post-resuscitation study period of 6 h (p < or = 0.05).
Myocardial inflammatory cytokines and iNOS activity increase during and after prolonged cardiac arrest and successful resuscitation. These increases correspond to the well described decrease in LV function post-resuscitation.
据报道，长时间心室颤动（VF）成功复苏后血清细胞因子会增加。促炎细胞因子可刺激诱导型一氧化氮合酶（iNOS）产生过量的一氧化氮（NO）。心肌炎性细胞因子和一氧化氮水平升高均可抑制心肌收缩功能。我们推测，长时间心室颤动心脏骤停成功复苏后，心肌促炎细胞因子和iNOS活性会增加，且这种增加与复苏后心肌功能障碍的发展平行。
在7头家猪（25±5 kg）中诱发心室颤动心脏骤停。未经治疗的VF持续10分钟后，对动物进行除颤和复苏。在复苏前、复苏期间和复苏后采集左心室（LV）收缩和舒张功能测量值、用于定量IL-8细胞因子的血清样本（动脉和冠状窦）以及LV心肌活检样本。使用免疫印迹分析确定心肌内皮型（eNOS）和诱导型（iNOS）一氧化氮合酶蛋白水平的定量，并使用免疫组织化学检查蛋白定位。
复苏后LV收缩和舒张功能降低，同时冠状窦IL-8水平和心肌iNOS活性均升高。与心脏骤停前的基线相比，iNOS蛋白水平在VF期间增加（p≤0.05），并在复苏后6小时的研究期间持续增加（p≤0.05）。
长时间心脏骤停及成功复苏期间和之后，心肌炎性细胞因子和iNOS活性增加。这些增加与复苏后LV功能下降的情况相符。
