OBJECTIVE: To assess the effects of Shenfu Injection (, 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 simultaneously 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 PaO₂ were 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 PaO₂ (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.
Blood Glucose ; Drugs, Chinese Herbal/therapeutic use* ; Heart Arrest/drug therapy* ; Humans ; Lactic Acid ; Post-Cardiac Arrest Syndrome

We described two patients who were successfully resuscitated from out-of-hospital cardiac arrest. Their ECGs showed ST elevations in V1 and aVR, as well as diffuse ST depression. Their ST elevation in V1 was noted to be greater than in aVR. While one patient was found to have an occlusion of the right ventricular (RV) branch of the right coronary artery, the other was found to have an occlusion of a proximal non-dominant right coronary artery supplying the RV branch. Successful primary percutaneous coronary intervention was performed for each patient with angioplasty and implantation of a drug-eluting stent. Both patients made good physical and neurological recovery.
Adult ; Angioplasty ; Angioplasty, Balloon, Coronary ; Cardiopulmonary Resuscitation ; Coronary Vessels ; physiopathology ; Defibrillators ; Drug-Eluting Stents ; Electrocardiography ; Heart Ventricles ; physiopathology ; Hepatitis B ; complications ; Humans ; Male ; Myocardial Infarction ; diagnosis ; physiopathology ; Out-of-Hospital Cardiac Arrest ; therapy ; Percutaneous Coronary Intervention ; Resuscitation ; Singapore

With the popularization of cardiopulmonary resuscitation (CPR) technology, the success rate of restoration of spontaneous circulation (ROSC) is gradually improved, and the survival rate and neurological outcome of patients with cardiac arrest are improved. Currently, therapeutic methods for cerebral resuscitation after cardiac arrest are limited. In addition to mild hypothermia for clinical application, the majority of drugs remain in the animal experimental stage. Finding effective brain protection drugs has become a hot spot in the field of brain resuscitation research. This article will review the pharmaceutical progress of research for cerebral resuscitation after cardiac arrest, so that we can study the brain protection mechanism of these drugs better and more targeted.
Cerebrovascular Circulation/drug effects* ; Heart Arrest/drug therapy* ; Humans ; Pharmaceutical Research/trends* ; Resuscitation/methods*

OBJECTIVETo investigate the effects of Shenfu Injection (, SFI) on cerebral metabolism in a porcine model of cardiac arrest (CA).

METHODSThirty Wuzhishan minipigs were randomly assigned to the control group (n=6), epinephrine group (EP group, n=12) and Sfigroup (n=12). After 8 min of untreated ventricular fifibrillation (VF), pigs in the EP group or Sfigroup were administered with either EP (0.02 mg/kg) or Sfi(1.0 mL/kg), respectively. After successful resuscitation, cerebrospinal fluid (CSF) levels of glucose, pyruvate, lactate, glutamate and glycerol were measured at 1, 6, 12 and 24 h after recover from spontaneous circulation (ROSC). In addition, neurologic defificit score (NDS) was calculated at 24 h after ROSC. Surviving pigs were killed at 24 h after ROSC, and the brain tissue was obtained for ultra-microstructure examination.

RESULTSCompared with the EP group, CSF glucose and pyruvate levels were higher (all P<0.01), and lactate levels were lower in the Sfigroup (P<0.01). Meanwhile, CSF glutamate and glycerol levels in the Sfigroup were lower in comparison to the EP group (all P<0.05). In addition, Sfidecreased NDS at 24 h after ROSC (P<0.01), and alleviated the histopathological damage of the brain.

CONCLUSIONSSficould alleviate brain injury after CA, which may be associated with improving cerebral metabolism.

Animals ; Blood Circulation ; Blood Gas Analysis ; Brain ; drug effects ; metabolism ; ultrastructure ; Cardiopulmonary Resuscitation ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Heart Arrest ; cerebrospinal fluid ; drug therapy ; physiopathology ; Injections ; Jugular Veins ; drug effects ; metabolism ; Perfusion ; Sus scrofa

OBJECTIVETo compare the effects of Shenfu Injection (SFI) and epinephrine (EPI) on catecholamine levels in a porcine model of prolonged cardiac arrest (CA).

METHODSAfter 8 min of untreated ventricular fibrillation, 24 Wuzhishan miniature pigs were randomly assigned to one of the three groups (n=8 per group) and received central venous injection, respectively: SFI group (1 mL/kg), EPI group (20 μg/kg EPI), and normal saline (NS) group. Cardiac output (CO), maximum rate of increase/decrease in left ventricular pressure (±dp/dt), serum levels of EPI, norepinephrine (NE), and dopamine (DA) were determined at baseline and at 0.5, 1, 2, and 4 h after restoration of spontaneous circulation.

RESULTSThe duration of cardiopulmonary resuscitation was shorter in the EPI and SFI groups than in the NS group (P<0.05). The EPI level increased significantly after restoration of spontaneous circulation (ROSC) in all three groups, and was significantly different between the EPI group and the other two groups immediately after ROSC (both P<0.01), but these differences gradually disappeared over time. There were no significant differences in NE or DA levels among the three groups, and there were no correlations between catecholamine levels and CO or dp/dt (P>0.05).

CONCLUSIONSSFI did not significantly affect endogenous catecholamine levels during cardiopulmonary resuscitation after prolonged ventricular fibrillation. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with EPI. SFI might be a potentially vasopressor drug for the treatment of CA.

Animals ; Cardiac Output ; drug effects ; Cardiopulmonary Resuscitation ; Catecholamines ; blood ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Epinephrine ; pharmacology ; therapeutic use ; Heart Arrest ; blood ; drug therapy ; Heart Ventricles ; physiopathology ; Injections ; Lactic Acid ; blood ; Sus scrofa

OBJECTIVETo investigate whether Shen-Fu Injection (, SFI) reduces post-resuscitation immune dysfunction in a porcine model of cardiac arrest by modulating apoptosis of regulatory T lymphocytes (Treg) in the spleen.

METHODSAfter 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 mL/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 mRNA 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).

RESULTSCompared with the sham group, the apoptosis rate of Treg was significantly decreased, and the levels of Foxp3 mRNA 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 mRNA expression, IFN-γ and IFN-γ/IL-4 (P<0.05).

CONCLUSIONSSFI has signifificant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.

Animals ; Apoptosis ; drug effects ; Cardiopulmonary Resuscitation ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Forkhead Transcription Factors ; genetics ; metabolism ; Heart Arrest ; drug therapy ; immunology ; pathology ; physiopathology ; Hemodynamics ; drug effects ; Injections ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Lymphocyte Subsets ; drug effects ; metabolism ; Male ; Oxygen ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Spleen ; immunology ; Survival Analysis ; Swine ; Swine, Miniature ; T-Lymphocytes, Regulatory ; drug effects ; immunology

Female ; Heart Arrest ; drug therapy ; etiology ; Humans ; Pulmonary Embolism ; complications ; Thrombolytic Therapy ; methods ; Young Adult

OBJECTIVETo test whether Shenfu Injection (, SFI) might attenuate the impact of cerebral energy dysfunction after resuscitation in a pig model of cardiac arrest (CA).

METHODSThirty-four Wuzhishan miniature inbred pigs were randomly divided into three groups: the SFI group (n=12), the saline group (SA group, n=12), and the sham-operated group (sham group, n=10). Following successful return of spontaneous circulation (ROSC) from 8-min untreated ventricular fibrillation, animals received a continuous infusion of either SFI (0.2 mL/min) or saline for 6 h. Cerebral performance category score was evaluated at 24 and 48 h after ROSC, followed by positron emission tomography and computed tomography scans of cerebral glucose uptake. Surviving pigs were euthanized 48 h after ROSC, and the brains were removed for detecting mitochondrial function.

RESULTSCompared with the SA group, SFI treatment produced a better neurologic outcome 48 h after ROSC (P<0.05). However, there was no significant difference of survival rate between the SA and SFI groups (83.3% vs. 81.8%, P>0.05). After ROSC, the SA group showed a decrease in the maximum standardized uptake value of different regions in the brain tissue, where SFI treatment can ameliorate these decreases (P<0.01 or P<0.05). Improved mitochondrial respiratory properties and higher mitochondrial membrane potential were also found following SFI treatment compared with the SA group at 48 h after ROSC (P<0.05 or P<0.01).

CONCLUSIONSFI treatment after resuscitation has significant neuroprotective effects against disruption of cerebral energy metabolism from CA by improving glucose uptake and by normalizing mitochondrial function.

Animals ; Brain ; diagnostic imaging ; metabolism ; Cardiopulmonary Resuscitation ; Drugs, Chinese Herbal ; therapeutic use ; Heart Arrest ; drug therapy ; Male ; Mitochondria ; physiology ; Neuroprotective Agents ; therapeutic use ; Positron-Emission Tomography ; Swine ; Swine, Miniature ; Tomography, X-Ray Computed

BACKGROUNDEpinephrine has been used as a first-choice vasopressor drug for cardiac arrest (CA) since 1974. However, the administration of epinephrine is controversial. This study aims to compare the effects of Shen-Fu injection (SFI) and epinephrine on resuscitation outcomes in a porcine model of prolonged CA.

METHODSVentricular fibrillation (VF) was electrically induced. After 8 minutes of untreated VF and 2 minutes of chest compressions, 24 pigs were randomly divided into 3 groups (n = 8 per group): central venous injection of SFI (SFI group), epinephrine (EPI group), or saline solution (SA group). The haemodynamic status and oxygen metabolism parameters, including cardiac output, mean arterial pressure, left ventricular dp/dtmax and negative dp/dtmax, oxygen delivery (DO2), and oxygen consumption (VO2), were calculated.

RESULTSSFI shortened the time to restoration of spontaneous circulation (ROSC) and decreased the number of shocks, similar to epinephrine. However, the mean arterial pressure, cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the EPI group at 4 and 6 hours after ROSC. VO2 and ERO2 decreased after ROSC and then increased. VO2 and ERO2 were significantly higher in the SFI group than in the EPI and SA groups after ROSC, while those were lowest in the EPI group among all groups.

CONCLUSIONSSFI shortened the time to ROSC and decreased the number of shocks, similar to epinephrine. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with epinephrine. SFI might be a potentially vasopressor drug for the treatment of CA.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Epinephrine ; administration & dosage ; pharmacology ; Heart Arrest ; drug therapy ; Injections, Intravenous ; Male ; Resuscitation ; methods ; Swine ; Treatment Outcome

Survival rates after cardiac arrest have not changed substantially over the past 5 decades. Postcardiac arrest (CA) syndrome (PCAS) is the primary reason for the high mortality rate after successful restoration of spontaneous circulation (ROSC). Intravenous administration of Shenfu Injection (, SFI) may attenuate post-CA myocardial dysfunction and cerebral injury, inhibit systemic ischemia/reperfusion responses, and treat underlying diseases. In this article, we reviewed the therapeutic effects of SFI in PCAS. SFI might be useful in the treatment of PCAS, incorporating the multi-link and multi-target advantages of Chinese medicine into PCAS management. Further experimental and clinical research to verify the therapeutic effects of SFI in PCAS is required.
Cardiotonic Agents ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Heart Arrest ; drug therapy ; physiopathology ; Humans ; Injections ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Syndrome