Effect Of Potassium Chloride On Cardiac Ischemia Reperfusion Injury After Cardiopulmonary Resuscitation In A Rat Cardiac Arrest Model

ObjectiveThe protective effect of potassium chloride on cardiac ischemia reperfusion injury was Confirmed in researches of organ level.However,it was not clear wether the administration of potassium chloride was also benefit to the heart after Cardiac arrest/Cardiopulmonary resuscitation（CA/CPR）.The Objective of our researches was to investigate the effect of potassium chloride on myocardial ischemia reperfusion injury during CA/CPR in a rat CA model.Methods1.To investigate the effect of potassium chloride on the changes of electrocardiogram（ECG）and Cardiopulmonary resuscitation（CPR）in a CA model.Sprague-Dawley（SD）rats with sustained Ventricular Fibrillation（VF）by electrical induction were randomly divided into two groups according to the method of random sampling:the potassium chloride solution group（KCL group,n=9）and the normal saline group（NS group,n=9）.While traditional CPR was started at 5 min after onset of electeical induction,the KCL group and the NS group were injected with 2.5%potassium chloride solution at a dose of 0.8mL/kg or equivalent normal saline via femoral vein followed by traditional CPR.The changes of electrocardiogram（ECG）,the spontaneous cardioversion rate,the calculative defibrillation energy,the defibrillation success rate,the time of Restoration of spontaneous circulation（ROSC）,the survival rate and the neurological deficit scores were compared between the two groups in ROSC 24h.2.To investigate the effects of potassium chloride on cardiomyocyte injury after CA/CPR from histology and molecular biology:The animals of CA group with sustained Pulseless Electrical Activity（PEA）by electrical induction were randomized into three groups according to method of random sampling:the saline group（NS group,n=16）,the low dose of potassium chloride group（LK group,n=16）,and the high dose of potassium chloride group（HK group,n=16）.Five min after onset of electeical induction,the LK group,the HK group and the NS group were injected with 1.25%potassium chloride solution at a dose of3.2mL/kg,2.5%potassium chloride solution at a dose of 3.2mL/kg or equivalent normal saline via femoral vein followed by traditional CPR.Anesthetization and intubation without CA/CPR were performed in 16 normal rats,which served as the sham group（SH group,n=16）.The concentration of basic serum potassium,the concentration of serum potassium after ROSC,and the serum Cardiac Tropin I（cTNI）,the myocardial histologic calmodulin（Ca M）content,Adenosine triphosphate（ATP）content,Ca²⁺-ATP enzyme activity and the Morphology of myocardial cells were compared between the four groups in Post ROSC 24 h.Results1.The results the first part researchAt the bebinning of CPR in the VF model,all animals of 2 groups show sustained VF with low amplitude（fine VF means amplitude<0.5mV）,VF amplitude were increased gradually to all animals in the 2 groups after CPR.The VF amplitude were significantly higher in the KCL group compared with the NS group at CPR 3min（P<0.05）.The VF amplitude decreased gradually in the two group with the extension of CPR time,however,the VF amplitude decreased more significantly in the NS group,the number of animal with fine VF in the KCL group was less than those of the NS group at CPR 7min（0 vs 5）.During CPR,the proportion of the VF spontaneous terminationin in the KCL group were increased,and the total proportion of successful cardioversion with electrical defilation were higher in the KCL group compared with the NS group（P<0.05）.The cumulative defibrillation energy was decreaed in the KCL group compared with the NS group（P=0.068）.the proportation of spontaneous circulation restoration（ROSC）time was shorter in the KCL group（P=0.096）,the mean arterial pressure were increased in the KCL group compared with the NS group during Post ROSC 1min and Post ROSC10min,and the survival rate in the in the KCL group increased（P<0.05）.2.The results the second part research2.1.Compared with the SH group at Post ROSC 2min,the concentration of serum potassium in NS、LK and HK group showed significantly increased（P<0.01）.Compared with the sham groups at Post ROSC 10 min,significant higher concentration of serum potassium were achived only in LK（P<0.01）and HK group（P<0.05）,while there was no statistice difference in the NS group.Compared with the NS group,the concentration of serum potassium in the LK showed significantly higher at Post ROSC 2min（P<0.01）and Post ROSC 10min respectively（P<0.05）.Compared with the NS group,the concentration of serum potassium in the HK also showed significantly higher at all observation time point after ROSC respectively（P<0.01）.The concentration of serum potassium in HK group was significantly higher at Post ROSC 2min compared with the LK group（P<0.01）.Although no stistical difference was observed between HK and LK group in concentration of serum potassium at Post ROSC 10min,the HK group still showed a mild increase compared with the LK group.2.2 The plasma cTNI The plasma cTNI significantly increased in the NS group,the LK group,and the HK group in Post ROSC 24h Compared with the SH group（P<0.01）;The plasma cTNI significantly decreased in the LK group and the HK group in Post ROSC 24h compared with the NS group（P<0.05）.2.3 The myocardial histologic CaM contentThe Ca M content were increased significantly in the NS group and the LK group compared with SH group in Post ROSC 24h（P<0.01）;The CaM content was significantly decreased in the HK group compared with NS group in Post ROSC 24h（P<0.01）;The CaM content was significantly decreased in the HK group compared with LK group in Post ROSC 24h（P<0.05）.2.4 The Myocardial histologic ATP contentThe Myocardial histologic ATP content were decreased significantly in the LK group and the NS group compared with the SH group in Post ROSC 24h（P<0.01）;The Myocardial histologic ATP content decreased significantly in the HK group compared with the NS group in Post ROSC 24h（P<0.01）;The Myocardial histologic ATP content decreased significantly in the HK group compared with the LK group in Post ROSC 24h（P<0.01）2.5 The Myocardial histologic Ca²⁺-ATP enzyme activity The Myocardial histologic Ca²⁺-ATP enzyme activity significantly decreased in the NS group,the LK group,and the HK group compared with the SH group in Post ROSC 24h（P<0.01）;The Myocardial histologic Ca²⁺-ATP enzyme activity were significantly increased in the LK group and the HK group compared with the NS group in Post ROSC 24h（P<0.05）2.6 Myocardial histologic cell morphologyMyocardial histologic were stained by hematoxylin and eosin in Post ROSC 24h,cytoplasmic staining was uneven,and the number of swelling nuclear was enlarge in the NS group.The cytoplasm was more even,the number of swelling nuclear was significantly reduced in LK group and the HK group,and the cell morphology was more close to the SH group in the HK group.ConclusionIncreasing serum potassium concentration may reduce the myocardial ischemia reperfusion injury by the following mechanisms in a rat CA/CPR model:Facilitates the VF amplitude enlargement,promotes the spontaneous conversion,reduce the cumulative defibrillation energy,increases the successful cardioversion with electrical defibrillation,creasing serum potassium concentration facilitaie the shorten ROSC time;correct abnormal calcium channel to anti calcium overload possibly through down-regulation CaM;Improve the nenergy metabolism of myocardial cells after ROSC.