Effects of Shenfu Injection(参附注射液)on Inflammatory Response during Post-Resuscitation Myocardial Dysfunction after Cardiac Arrest in Swine

Objective:To investigate whether Shenfu Injection(SFI,参附注射液)can alleviate post-resuscitation myocardial dysfunction by inhibiting the inflammatory response.Methods:After 8 min of ventricular fibrillation and 2 min of basic life support,24 pigs were randomly divided into 3 groups(n=8),which were given intravenous bolus injections of SFI(1.0 mL/kg),epinephrine(EP,0.02 mg/kg)and normal saline(SA),respectively.The animals were sacrificed at 24 h after restoration of spontaneous circulation(ROSC),and serum interleuking-6(IL-6)and tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay(ELISA);expressions of Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)m RNAs and proteins were determined by RT-PCR and Western blot,respectively.Results:Compared with the EP and the SA groups,the ultrastructure of myocardial cells were slightly damaged and the systolic function of the left ventricle was markedly improved in the SFI group at 24 h after ROSC(P<0.05).In addition,compared with the EP and SA groups,the SFI group also showed significantly reduced levels of serum IL-6 and TNF-α,protein and mRNA levels of myocardial NF-κB and TLR4(P<0.05).Conclusions:Activation of TLR4/NF-κB signaling pathway may be involved in the pathological mechanisms of post-resuscitation myocardial dysfunction.SFI may block NF-κB-mediated inflammatory response by reducing the activity of NF-κB and the level of TNF-α,thus playing a protective role in post-resuscitation myocardial dysfunction.

Effects of Shen-Fu Injection (参附注射液) on Apoptosis of Regulatory T Lymphocytes in Spleen during Post-Resuscitation Immune Dysfunction in A Porcine Model of Cardiac Arrest

Objective： To investigate whether Shen-Fu Injection（参附注射液, SFI） reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes（Treg） in the spleen. Methods： After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs were divided into 3 groups with a random number table, i.e. SFI group, epinephrine（EP） group, and saline（SA） group（8 in each group）, which received central venous injection of SFI（1.0 m L/kg）, EP（0.02 mg/kg） and SA, respectively. The same procedure without CA initiation was achieved in the sham-operated（sham） group（n=6）. After successful return of spontaneous circulation（ROSC）, apoptosis rate of splenic Treg was detected by flow cytometry; and the m RNA expression of forkhead/winged helix transcription factor（Foxp3） of splenic Treg was detected by real time-polymerase chain reaction; and the levels of interleukin-4（IL-4） and interferon-γ（IFN-γ） in porcine splenic Treg were detected by using enzyme-linked immunosorbent assay（ELISA）. Results： Compared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 m RNA expression, IFN-γ, IL-4 and IFN-γ/IL-4 were increased in the SA group（P〈0.05 or P〈0.01）. Compared with the EP and SA groups, SFI treatment increased the apoptosis rate of Treg and reduced the levels of Foxp3 m RNA expression, IFN-γ and IFN-γ/IL-4（P〈0.05）. Conclusions： SFI has significant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.

Cardiac arrest, stony heart, and cardiopulmonary resuscitation: An updated revisit

The post-resuscitation period is recognized as the main predictor of cardiopul-monary resuscitation(CPR)outcomes.The first description of post-resuscitation syndrome and stony heart was published over 50 years ago.Major manifestations may include but are not limited to,persistent precipitating pathology,systemic ischemia/reperfusion response,post-cardiac arrest brain injury,and finally,post-cardiac arrest myocardial dysfunction(PAMD)after successful resuscitation.Why do some patients initially survive successful resuscitation,and others do not?Also,why does the myocardium response vary after resuscitation?These ques-tions have kept scientists busy for several decades since the first successful resuscitation was described.By modifying the conventional modalities of resu-scitation together with new promising agents,rescuers will be able to salvage the jeopardized post-resuscitation myocardium and prevent its progression to a dismal,stony heart.Community awareness and staff education are crucial for shortening the resuscitation time and improving short-and long-term outcomes.Awareness of these components before and early after the restoration of circulation will enhance the resuscitation outcomes.This review extensively addresses the underlying pathophysiology,management,and outcomes of post-resuscitation syndrome.The pattern,management,and outcome of PAMD and post-cardiac arrest shock are different based on many factors,including in-hospital cardiac arrest vs out-of-hospital cardiac arrest(OHCA),witnessed vs unwitnessed cardiac arrest,the underlying cause of arrest,the duration,and protocol used for CPR.Although restoring spontaneous circulation is a vital sign,it should not be the end of the game or lone primary outcome;it calls for better understanding and aggressive multi-disciplinary interventions and care.The development of stony heart post-CPR and OHCA remain the main challenges in emergency and critical care medicine.

Effect of Shenfu Injection(参附注射液)on Lactate and Lactate Clearance in Patients with Post-cardiac Arrest Syndrome:A Post Hoc Analysis of a Multicenter Randomized Controlled Trial

Objective: To assess the effects of Shenfu Injection(参附注射液, SFI) on blood lactate, and secondarily its effect on the lactate clearance(LC) in patients with post cardiac arrest syndrome(PCAS). Methods: The present study is a post hoc study of a randomized, assessor-blinded, controlled trial. Patients experienced in-hospital cardiac arrest between 2012 and 2015 were included in the predefined post hoc analyses. Of 1,022 patients enrolled, a total of 978 patients were allocated to the control group(486 cases) and SFI(492 cases) group, receiving standardized post-resuscitation care bundle(PRCB) treatment or PRCB combined with SFI(100 mL/d), respectively. Patients’ serum lactate was measured simutaneously with artery blood gas, lactate clearance(LC) was calculated on days 1, 3, and 7 after admission and compared between groups. Lactate and LC were also compared between the survivors and non-survivors according to the 28-d mortality, as well as the survivors and non-survivors subgroups both in the SFI and control groups. Results: In both groups, compared with pre-treatment levels, mean arterial pressure(MAP) and PaOwere significantly improved on 1, 3, 7 d after treatment(P<0.05), while heart rate(HR) and blood glucose levels were significantly decreased on 1, 3 and 7 d after treatment(P<0.05). compared with control group, SFI treatment improved the values of MAP and PaO(P<0.05), and significantly decreased the levels of HR and the blood glucose level on 3 and 7 d after treatment(P<0.05). Compared with the control group, lactate levels decreased faster in the SFI group versus the control group on 3 and 7 d(P<0.05). From initiation of treatment and the following 3 and 7 d, SFI treatment greatly increased the LC compared with that in the control group(P<0.05). Compared with survivors, non-survivors had higher admission lactate levels(7.3±1.1 mmol/L vs. 5.5±2.3 mmol/L;P <0.01), higher lactate levels on days 1, 3 and 7(P <0.05), and LC were decreased significantly on 3 and 7 d after treatment(P<0.05). Similar results were also found both in the SFI and control groups between survivors and non-survivors subgroups. Conclusion: SFI in combination with PRCB treatment is effective at lowering lactate level and resulted in increasing LC in a targeted population of PCAS patients.