Effect of Shenfu on inflammatory cytokine release and brain edema after prolonged cardiac arrest in the swine

Hou, Xiaomin; Li, Chunsheng; Gu, Wei; Guo, Zhijun; Yin, Wang; Zhou, Da

doi:10.1016/j.ajem.2013.03.020

Cited by 27 publications

(18 citation statements)

References 32 publications

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“…The main active ingredients of Shen-Fu injection are ginsenoside and aconitine ( 114 ). Previous studies have reported that Shen-Fu injection can minimize PCAS-associated brain edema ( 115 ), myocardial dysfunction ( 116 ), and lung injury ( 117 ). Shen-Fu injection was also found to inhibit the coagulofibrinolytic changes associated with PCAS, which might be involved in attenuating endothelial dysfunction and improving the systemic metabolism ( 114 ).…”

Section: Coagulofibrynolitic System As a Therapeutic Target For Pcasmentioning

confidence: 99%

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Wada

2017

Front. Med.

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Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which consists of four syndromes including systemic ischemia/reperfusion responses and post-cardiac arrest brain injury. The major pathophysiologies underlying systemic ischemia/reperfusion responses are systemic inflammatory response syndrome and increased coagulation, leading to disseminated intravascular coagulation (DIC), which clinically manifests as obstruction of microcirculation and multiple organ dysfunction. In particular, thrombotic occlusion in the brain due to DIC, referred to as the “no-reflow phenomenon,” may be deeply involved in post-cardiac arrest brain injury, which is the leading cause of mortality in patients with PCAS. Coagulofibrinolytic changes in patients with PCAS are characterized by tissue factor-dependent coagulation, which is accelerated by impaired anticoagulant mechanisms, including antithrombin, protein C, thrombomodulin, and tissue factor pathway inhibitor. Damage-associated molecular patterns (DAMPs) accelerate not only tissue factor-dependent coagulation but also the factor XII- and factor XI-dependent activation of coagulation. Inflammatory cytokines are also involved in these changes via the expression of tissue factor on endothelial cells and monocytes, the inhibition of anticoagulant systems, and the release of neutrophil elastase from neutrophils activated by inflammatory cytokines. Hyperfibrinolysis in the early phase of PCAS is followed by inadequate endogenous fibrinolysis and fibrinolytic shutdown by plasminogen activator inhibitor-1. Moreover, cell-free DNA, which is also a DAMP, plays a pivotal role in the inhibition of fibrinolysis. DIC diagnosis criteria or fibrinolysis markers, including d-dimer and fibrin/fibrinogen degradation products, which are commonly tested in patients and easily accessible, can be used to predict the mortality or neurological outcome of PCAS patients with high accuracy. A number of studies have explored therapy for this unique pathophysiology since the first report on “no-reflow phenomenon” was published roughly 50 years ago. However, the optimum therapeutic strategy focusing on the coagulofibrinolytic changes in cardiac arrest or PCAS patients has not yet been established. The elucidation of more precise pathomechanisms of coagulofibrinolytic changes in PCAS may aid in the development of novel therapeutic targets, leading to an improvement in the outcomes of PCAS patients.

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Section: Coagulofibrynolitic System As a Therapeutic Target For Pcasmentioning

confidence: 99%

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Wada

2017

Front. Med.

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“…In addition, Shenfu can improve the immune function in the lungs [ 31 ]. Shenfu can decrease the expression of TNF- α , block malignant inflammation, improve the microcirculation, and extend the time of tissue and cellular viability without oxygen [ 32 ]. In addition, Shenfu may improve recovery of immunologic function by balancing cytokine secretion [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open‐Label Trial

Zhang

Lin

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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The effect of Shenfu on biochemical parameters and survival during resuscitation in patients with septic shock was examined. This was a multicenter, controlled, randomized, open-label trial carried out in 210 patients with septic shock from seven medical centers in China. They were randomized to Shenfu or saline. The primary outcome was lactate clearance. The secondary outcomes were shock index normalization, dose of vasopressors, ICU stay, hospital stay, and mortality. A total of 199 patients completed the trial. Blood pressure, heart rate, and other routine lab tests showed no difference between the groups. Lactate levels and lactate clearance were similar between the two groups. Hospital and ICU stay were similar between the two groups. When considering all patients, the 7- and 28-day mortality were similar between the two groups, but when considering only patients with lactate levels ≥4.5 mmol/L, the Shenfu group showed a better 7-day survival than the control group (7 days: 83.3% versus 54.5%, P = 0.034; 28 days: 72.7% versus 47.6%, P = 0.092). Shenfu may improve the 7-day survival in patients with impaired lactate clearance (≥4.5 mmol/L), but the mechanism for this effect is unclear. Additional studies are necessary to characterize the hemodynamic changes after Shenfu infusion. This trial is registered with ChiCTR-TRC-11001369.

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“…Shen-Fu injection is a typical form of SFI decoction for intravenous medication. The effects of SFI are based on aconitine properties, supplemented by ginsenoside, which can reduce local inflammation and brain edema after cerebral ischemia [ 15 ]. The protective mechanisms of SFI against cerebral ischemia/reperfusion injury include reduced excitatory amino acid toxicity, blockade of Ca 2+ overload, and improved antioxidant capacity [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Shen‐Fu Injection on Neuronal Mitochondrial Function in a Porcine Model of Prolonged Cardiac Arrest

Hou

Zhou

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Background. Shen-Fu injection (SFI) following cardiac arrest exhibits neurological effects, but its effect on neurological dysfunction is unclear. This study sought to investigate the protective effect of SFI on nerve cells in a porcine model of cardiac arrest. Methods. After eight minutes of untreated ventricular fibrillation (VF) and 2 minutes of basic life support, 24 pigs were randomized and divided into three cardiopulmonary resuscitation groups, which received central venous injection of either Shen-Fu (SFI group; 1.0 ml/kg), epinephrine (EP group; 0.02 mg/kg), or saline (SA group). Surviving pigs were sacrificed at 24 h after ROSC and brains were removed for analysis for morphologic changes of mitochondria by electron microscopy, for mitochondrial transmembrane potential (MTP) by flow cytometry, and for opening of the mitochondrial permeability transition pore (MPTP) by mitochondrial light scattering. Results. Compared with the EP and SA groups, SFI treatment reduced opening of MPTP, showing higher MMP. In addition, animals treated with SFI showed slight cerebral ultrastructure damage under the electron microscopy. Conclusion. Shen-Fu injection alleviated brain injury, improved neurological ultrastructure, stabilized membrane potential, and inhibited opening of MPTP. Therefore, SFI could significantly attenuate postresuscitation cerebral ischemia and reperfusion injury by modulating mitochondrial dysfunction of nerve cells.

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Effect of Shenfu on inflammatory cytokine release and brain edema after prolonged cardiac arrest in the swine

Cited by 27 publications

References 32 publications

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Effects of Shenfu Injection in the Treatment of Septic Shock Patients: A Multicenter, Controlled, Randomized, Open‐Label Trial

Protective Effect of Shen‐Fu Injection on Neuronal Mitochondrial Function in a Porcine Model of Prolonged Cardiac Arrest

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