The Change Of Cardiac Rhethm During Asphyxial Cardiac Arrest And The Correlation Between Resuscitation And Stress Hormone

Background:Asphyxial cardiac arrest (CA) are caused by a diversity of pathophysiological processes leading to asphyxia, which preclude movement of gas from the upper airway to the alveoli and ultimately to the tissues, the cell, and then to the mitochondria, thereby sustaining oxidative metabolism in vital organ, including drowning, drug-induced apnea, allergic disease of the airways, et al. In comparison with the sudden cardiac death caused by ventricular fibrillation(VF), the process from asphyxia developing into CA is longer and more aggressive. The severity and persistence of hypoxemia and hypercarbia characterized by asphyxial CA completely destroy the function of important organs and make the successful resuscitation difficult.The outcomes of resuscitation are different according to the specific etiologies of CA. It's necessary for the increasing rate of return of spontaneous circulation (ROSC) to understand the process of pathophysiology characterized by asphyxial CA. The timing and spectrum of change of cardiac rhythm from the onset of asphyxial CA to the initiation of CPR is important information, based on which we can decide the optimal strategy of the subsequent CPR and proper vasopressors. It's crucial of the application of vasopressors during CPR to improve the rate of ROSC. The application of epinephrine or vasopressin in different animal models of asphyxial CA demonstrated varying outcomes of resuscitation, which implied that there is no confirmed conclusion about which one of epinephrine and vasopressin would bring better effect to the asphyxial CA. The combination of epinephrine and vasopressin showed significantly higher rate of ROSC in a pediatric pig model of VF than epinephrine or vasopressin alone, which inspired us that whether epinephrine administrated with vasopressin in asphyxial CA would bring out better outcome of resuscitation just as in the VF model, and therefore would it be a new pharmacologic strategy of asphyxial CA? It's necessary to verify it in adult pig model of asphyxial CA. CA could evoke the severest stress response of human, in which large amount of stress hormones involved, and affected the outcome of resuscitation. The concentrations of adrenocorticotropic hormone (ACTH), cortisol and angiotensinⅡ(AngⅡ)are positively correlative with the rate of ROSC in the sudden cardiac death and the animal model of VF. However, in the asphyxial CA, how the concentration of the above three stress hormones changes, what effect they have on the outcomes of resuscitation, and how they response to the vosopressors remain unclear.The research consists of three parts. Firstly, to observe the cardiac rhythms of rats,rabbits and pigs during the asphyxial CA; Secondly, to explore the effect of combination of vasopressors and vasopressor alone in the asphyxial CA; finally, to determine what effect of different vasopressors have on ACTH, cortisol and AngⅡduring the asphyxial CA.Part one: The change of cardiac rhythms in the asphyxial CA Objective: to observe the change of cardiac rhythms during the asphyxial CA in different species of animals via establishing the asphyxial CA model of rats,rabbits and pigs.Method: 30 rats,30 rabbits and 20 pigs were acutely asphyxiated by endotracheal tube clamping until 5min after coming to the criterion of CA. CPR was then provided. Epinephrine was administrated to the three species of animals after 3min of CPR and repeated intravenously every other 5min. Record the time from the initiation of clamping endotracheal tube to the onset of CA (TCA), the time from the start of CPR to the ROSC(TROSC) and the rate of ROSC in three groups; the cardiac rhythms in rats,rabbits and pigs were recorded at the onset of CA and prior to CPR, including VF/pulseless ventricular tachycardia( Pulseless VT), pulseless electrical activity(PEA) and asystole. Result: TCA,TROSC and the rate of ROSC were 4.48±0.38min,2.44±0.98min and 33.3% in rats, 6±1min,5.95±0.75min and 30% in rabbits, 13.46±2.7min,16.14±1.2min and 15% in pigs.Cardiac rhythms of three groups of animals at the different time point: The moment of onset of CA: 29 rats showed PEA and the rest one present VF; 29 rabbits demonstrated PEA and the rest one showed VF; 12 pigs indicated PEA, VF in 4 and asystole in 4.Prior to CPR: there are PEA of 6 and asystole of 24 in 30 rats. 25 rabbits showed PEA and the rest 5 present aystole. 13 pigs demonstrated VF, PEA in 3 and aystole in the rest 4. The incidence of asystole in rats was significantly highe -r than the rabbits and the pigs (P<0.05). The rate of PEA in rabbits was sign -ificantly higher than the rats and the pigs. The rate of VF in pigs was highest among three groups of animals.Conclusion: the different species of animals demonstrated different cardiac rhythms during the asphyxial CA. At the onset of CA, most of rats,rabbits and pigs showed PEA, however, as the asphyxia prolonged, the obvious changes happened in three groups of animals: most of pigs converted to VF,most of rats altered to asystole and most of rabbits still in PEA.Part two: The effect of epinephrine combined with vasopressin in adult pig model of asphyxial CAObjective: to observe the effect of combination of epinephrine and vasopressin in the asphyxial CA, and decide what difference between the combination of vasopressors and the vasopressor alone in resuscition via producing the adult pig model of asphyxial CA.Method: Clamping of the endotracheal tube was applied on 24 adult male pigs to establish the model of asphxial CA. After 3 minutes of CPR, 24 animals were randomly assigned to receive either epinephrine (epinephrine group, 45μg/kg, n=8), vasopressin (vasopressin group, 0.4U/kg, n=8), or epinephrine combined with vasopressin (vasopressin/epinephrine combination group;μg/kg and U/kg: 45 and 0.4, n=8). All drugs were diluted to 10 ml with normal saline and injected separately intravenously at 5-minute intervals. Record the TCA, the TROSC and the rate of ROSC in the three groups; Mean artery pressure(MAP),blood-gas analysis,Coronary perfusion pressure (CPP) and the pressure of end-tidal Carbon dioxide (PETCO2) were measured before induction of cardiac arrest, at 2 minutes of CPR, and at 90 seconds and 5 minutes after the first-dose drug administration.Result: TCA,TROSC and the rate of ROSC were 16.24±2.31min,17.14min and 12.5% (1 ROSC) in the epinephrine group; 15.75±1.45min,16.89min and 12.5%(1 ROSC) in the vasopressin group; 16.98±2.05min,13.56±2.14min and 100%(8 ROSC) in the epinephrine/vasopressin combination group.MAP and PaO2 after first-dose drug administration in the combination group were significantly higher than 2min after CPR (P<0.05), while PaCO2 was significantly lower than 2min after CPR (P<0.05). MAP and PaO2 at 90 sec and 5min after first dose drug administration were significantly higher than the epinephrine group (P<0.05) and the vasopressin group (P<0.05), while PaCO2 was significantly lower than the other two groups.Both CPP and PETCO2 of the three groups increased after administration of vasopressors, coming to the climax at the 90sec after drug administration. The combination group maintained the highest level of the above two parameters after the vasoprissors repeated during the rest of the resuscitation. CPP and PETCO2 of the vasopressin group were higher than the epinephrine group, but they couldn't maintain high level even after repeating the vasopressin. The epinephrine group remained the lowest level among the three groups during the whole process of CPR.Conclusion: the combination of epinephrine and vasopressin significantly incre- ased the rate of ROSC in the adult pig model of asphyxial CA, and improved obviously ventilation/perfusion and hypercarbia during the resuscition. The effect of epinephrine administrated with vasopressin is better than the vasopressor alone in the CPR.Part three: The correlation of the stress hormone and the outcome of asphyxial CAObjective: to observe what impact of epinephrine, vasopressin or both of them have on the concentration of ACTH, cortisol and AngⅡat the different time point during the resuscitation via establishing the adult pig model of asphyxial CA. Method: 24 adult male pigs were elected to produce the model of acute asphxial CA. The preparation of animal and the grouping were same to the part two. ACTH,cortisol and AngⅡmeasured for three groups of pigs( epinephrine group,vasopressin group and epinephrine/vasopressin combination group)were measured before inducing cardiac arrest, at 2 minutes of CPR, at 90 seconds and 5 minutes after the drug administration, and at 30minutes after ROSC. ACTH was measured by immunoradiometric assay (IRMA), cortisol by chemiluminesc -ence immunoassay(CIA), and AngⅡby radio immunoassay (RIMA).Result: TCA, TROSC and the rate of ROSC in the three groups can be found in the part two.The concentration of ACTH, cortisol and AngⅡof the three groups during CPR:ACTH: the concentrations of ACTH at 2min of CPR in the three groups resembled before the asphyxia. After the first-dose of drug administration, ACTH of the combination group and the vasopressin group increased, 90sec significantly higher than CPR2min (P<0.05). The combination group remained the highest level of ACTH until ROSC 30min. ACTH in the vasopressin group came up to the climax at 90 sec after the first-dose of drug administration, but fell after drug repeated. The epinephrine group remained the lowest level of ACTH among the three groups. The concentration of ACTH in the combination group at the different time points after drug were significantly higher than the orther two groups (P<0.05). The vasopressin group was significantly higher than the epinephrine group (P=0.027) at the 90sec after the first-dose drug.Cortisol: the concentrations of cortisol at 2min of CPR in the three groups were a little higher than before the asphyxia. After the first-dose of drug administration, cortisol of the combination group and the vasopressin group increased, 90sec significantly higher than CPR2min (P<0.05). The combination group remained high level of cortisol until ROSC 30min. Cortisol in the vasopressin group came up to the climax at 90 sec after the first-dose of drug administration, but fell after drug repeated. Cortisol in the epinephrine group after drug administration resembled CPR2min, and repeating administration can't increase the concentration of cortisol. The concentration of cortislo in the combination group at the different time points after drug were significantly higher than the other two groups (P<0.05). The vasopressin group was significantly higher than the epinephrine group (P=0.018) at the 90sec after the first-dose drug.AngⅡ: AngⅡof the three groups at CPR 2min was a little higher than before asphyxia. After the first-dose of drug, the three groups increased, 90sec significantly higher than CPR2min (P<0.05). Repetition of drug administration increased the concentration of AngⅡin the combination group, but descent in the epinephrine group and the vasopressin group. The concentration of AngⅡin the combination group at the different time points after drug were significantly higher than the orther two groups (P<0.05). The epinephrine group was significantly higher than the vasopressin group (P=0.018) since the 90sec after the second-dose drug (P<0.05).The concentration of ACTH, cortisol and AngⅡin the pigs with ROSC were significantly higher than the pigs without ROSC at the different time points after drug in the CPR (P<0.01).Conclusion: the concentrations of ACTH, cortisol and AngⅡduring the asphyxial CA were correlative with the rate of ROSC. The higher concentrations of hormores showed, the higher the rate of ROSC. The concentration of ACTH, cortisol and AngⅡin the combination group at the different time points after drug in the CPR were significantly higher than the epinephrine group and the vasopressin group, suggesting that increasing the concentrations of stress hormones may be one of mechanisms responsible for the better resuscitative effect of combined vasopressors.