title: Cardioprotective effect of nicorandil against myocardial injury following cardiac arrest in swine.
abstract: BACKGROUND
  Nicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia-reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation.
  
  
  METHODS
  Ventricular fibrillation was induced electrically for 4min in anesthetized domestic swine, followed by cardiopulmonary resuscitation. Sixteen successfully resuscitated animals were randomized to saline control (n=8) or nicorandil (n=8) groups. Nicorandil (150μg/kg) was administered by central intravenous injection at onset of restoration of spontaneous circulation (ROSC), followed by 3μg/kg/min infusion until reperfusion end. Sham-operated animals received surgery only (n=4). Hemodynamic parameters were monitored continuously. Blood samples were taken at baseline, 5, 30, 180, and 360min after ROSC. Left ventricular ejection fraction was assessed by echocardiography at baseline and 6h after ROSC. The animals were euthanized 6h after ROSC, and the cardiac tissue was removed for analysis.
  
  
  RESULTS
  6 h after ROSC, nicorandil had significantly improved all hemodynamic variables (all P<0.05) except the maximum rate of left ventricular pressure decline and heart rate (P>0.05) compared with the control group. Control animals showed elevated cardiac troponin I and lactate levels compared with sham animals, which were significantly decreased following nicorandil treatment (P<0.05). In the saline control group, the adenosine triphosphate (ATP) content was largely reduced but subsequently rescued by nicorandil (P<0.05). Histopathologic injury was reduced with nicorandil treatment. Nicorandil reduced cardiomyocyte apoptosis as evidenced by reduced terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, decreased Bax and caspase-3 expression, and increased Bcl-2 expression in the myocardium (all P<0.05).
  
  
  CONCLUSIONS
  Nicorandil exhibited cardioprotective effects on myocardial injury following cardiac arrest via improvement in post-resuscitation myocardial dysfunction and energy metabolism, reduction in myocardial histopathologic injury, and antiapoptotic effects.
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Li-Ning
authors.initials: LN
authors.lastname: Liang
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Hou
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Hao-Ran
authors.initials: HR
authors.lastname: Hu
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Zhu
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China.
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Chen
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China. Electronic address: Sdslyyjxf123@163.com.
authors.forename: Xian-Fei
authors.initials: XF
authors.lastname: Ji
authors.affiliation: Department of Emergency, Shandong Provincial Hospital affiliated to Shandong University, No. 324, Jingwu Road, Jinan 250021, Shandong, China. Electronic address: Sdslyysdy123@163.com.
authors.forename: De-Ya
authors.initials: DY
authors.lastname: Shang
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000473:pathology*; D007275:Injections, Intravenous; D008297:Male; D020108:Nicorandil / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014693:Ventricular Fibrillation / Q000473:pathology*
chemical_list: D002316:Cardiotonic Agents; D020108:Nicorandil
keywords: Cardiac arrest; Myocardial injury; Nicorandil; Swine