Adenoviral βARKct Cardiac Gene Transfer Ameliorates Post-resuscitation Myocardial Injury in a Porcine Model of Cardiac Arrest.
Adenoviral βARKct Cardiac Gene Transfer Ameliorates Post-resuscitation Myocardial Injury in a Porcine Model of Cardiac Arrest.
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DOI：
10.1097/shk.0000000000001320
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发表时间：
2019-01
期刊：
影响因子：
3.1
通讯作者：
De-ya Shang;Fangfang Zhu;Qi Tan;Bo Hu;Dong-Xing Liu;Mulin Cong;Jiantao Song;Tao Li;Xian-fei Ji
中科院分区：
文献类型：
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作者：
De-ya Shang;Fangfang Zhu;Qi Tan;Bo Hu;Dong-Xing Liu;Mulin Cong;Jiantao Song;Tao Li;Xian-fei Ji
目的观察腺病毒βARKct心脏基因转移抑制G蛋白偶联受体激酶2能否改善心脏骤停(CA)猪复苏后心肌损伤，探讨其心肌保护机制。方法雄性长白家猪随机分为假手术组(麻醉后用药，但不诱发室颤)(n=4)、对照组(室颤8min，n=8)和βARKct组(室颤8min，n=8)。连续监测血流动力学参数。分别于基础状态、自主循环恢复后30min、2 h、4 h、6 h采集血样。分别于术前和术后6h用超声心动图测定左心室射血分数。于ROSC后6h处死动物，取出心肌组织进行分析。结果与假手术组比较，恢复自主循环后6h，对照组和β组的左心室+dp/dtmax、-dp/dtmax、心输出量(CO)和射血分数(EF)均显著降低。而β组术后左心室+dp/dt_(Max)、-dp/dt_(Max)、CO和EF较对照组明显改善。βARKCT治疗后血清心肌肌钙蛋白I、CK-MB、乳酸水平也明显降低。此外，与对照组相比，腺病毒-βARKct治疗组动物的β-1肾上腺素能受体、SERCA2a、RyR2水平升高，GRK2水平下降。结论腺病毒βARKct心脏基因转移抑制GRK2对复苏后心肌损伤有一定的保护作用，其机制可能与恢复心肌细胞肌浆网钙调节蛋白的表达和上调β1肾上腺素能受体水平有关。
OBJECTIVE To determine whether the inhibition of the G protein-coupled receptor kinase 2 by adenoviral βARKct cardiac gene transfer can ameliorate post-resuscitation myocardial injury in pigs with cardiac arrest (CA) and explore the mechanism of myocardial protection. METHODS Male landrace domestic pigs were randomized into the sham group (Anesthetized and instrumented, but ventricular fibrillation was not induced) (n = 4), control group (ventricular fibrillation 8 min, n = 8) and βARKct group (ventricular fibrillation 8 min, n = 8). Hemodynamic parameters were monitored continuously. Blood samples were collected at baseline, 30 min, 2 h, 4 h, and 6 h after the return of spontaneous circulation (ROSC). Left ventricular ejection fraction was assessed by echocardiography at baseline and 6 h after ROSC. These animals were euthanized, and the cardiac tissue was removed for analysis at 6 h after ROSC. RESULTS Compared with those in the sham group, left ventricular +dp/dtmax, -dp/dtmax, cardiac output (CO), and ejection fraction (EF) in the control group and the βARKct group were significantly decreased at 6 h after the restoration of spontaneous circulation. However, the βARKct treatment produced better left ventricular +dp/dtmax, -dp/dtmax, CO and EF after ROSC. The βARKct treatment also produced lower serum cardiac troponin I, CK-MB, lactate after ROSC. Furthermore, in comparison with the control group, the adenoviral-βARKct treated animals showed increased levels of β1 adrenergic receptor, SERCA2a, RyR2 and decreased the level of GRK2. CONCLUSIONS The inhibition of GRK2 by adenoviral βARKct cardiac gene transfer can ameliorate post-resuscitation myocardial injury through beneficial effects on restoring the sarcoplasmic reticulum Ca-handling proteins expression and upregulating the β1- adrenergic receptor level after cardiac arrest.