Effect of mild hypothermia on inositol requiring enzyme 1 signaling pathway during myocardial injury after cardiac arrest and resuscitation in swine / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of mild hypothermia on inositol-requiring enzyme 1 (IRE1) signaling pathway during myocardial injury after cardiac arrest and resuscitation in swine.Methods Twenty-one healthy male white swine,weighing 33-41 kg,were divided into 3 groups using a random number table method:sham operation group (group S,n =5),cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR,n=8),and mild hypothermia group (group MH,n=8).The model of cardiac arrest and resuscitation was established based on the previously reported method.The catheters placed in the left femoral artery and right internal jugular vein were connected to the PiCCO Monitor system,and another pacing catheter was advanced from the right external jugular vein into the right ventricle.Ventricular fibrillation was induced by using a 1 mA alternating current through the pacing catheter.Once ventricular fibrillation was successfully induced,mechanical ventilation was discontinued for 8 min,and then cardiopulmonary resuscitation was initiated.Epinephrine 20 μg/kg was administered at 2.5 min of resuscitation followed by repetition every 3 min.Defibrillation was delivered at 5 min of resuscitation,and then spontaneous circulation was evaluated.If return of spontaneous circulation was not achieved,cardiopulmonary resuscitation was immediately resumed for 2 min and then defibrillation was delivered again.Mechanical ventilation was continued for 30 h after successful resuscitation.Animals in group S only underwent surgical preparation without experiencing cardiac arrest and resuscitation.At 5 min after successful resuscitation,body temperature was cooled down to 33 ℃ by using a cooling blanket,and then maintained at this level until 24 h after resuscitation,followed by 5 h of re-warming at a rate of 1 ℃/h in group MH.The temperature was maintained at 37.5-38.5 ℃ with the aid of surface cooling blanket in the other two groups.At 1,6,12,24 and 30 h after resuscitation (T1-5),the values of stroke volume (SV) and global ejection fraction (GEF) were recorded,and meanwhile 2 ml of blood samples was obtained via the femoral vein to measure the concentration of serum cardiac troponin Ⅰ (cTnI) (by enzyme-linked immunosorbent assay) and activity of serum creatine kinase-MB (CK-MB) (by immunosuppression).The swine were sacrificed at 30 h after resuscitation,and then myocardial specimens from the left ventricle were obtained for determination of the expression of caspase-3 (by immunohistochemistry),cell apoptosis (by TUNEL),and expression of IRE1 and casepase-12 (by Western blot).Apoptosis index was calculated.Results Compared with group S,SV and GEF were significantly decreased and the serum CK-MB activity was increased at T1-5,the concentration of serum cTnI was increased at T2-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was up-regulated,and apoptosis index was increased in CA-CPR and MH groups (P＜0.05).Compared with group CA-CPR,the SV and GEF were significantly increased and the concentration of serum cTnI was decreased at T2-5,the activity of serum CK-MB was decreased at T3-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was down-regulated,and apoptosis index was decreased in group MH (P＜0.05).Conclusion The mechanism by which mild hypothermia mitigates myocardial injury after cardiac arrest and resuscitation may be related to inhibiting IRE1 signaling pathway in swine.