Therapeutic Effects of Shenfu Injection in Shock.

Shock is the clinical manifestation of acute circulatory failure, which results in inadequate utilization of cellular oxygen. It is a common condition with high mortality rates in intensive care units. The intravenous administration of Shenfu Injection (SFI) may attenuate inflammation, regulate hemodynamics and oxygen metabolism; inhibit ischemia-reperfusion responses; and have adaptogenic and antiapoptotic effects. In this review, we have discussed the clinical applications and antishock pharmacological effects of SFI. Further in-depth and large-scale multicenter clinical studies are warranted to determine the therapeutic effects of SFI on shock.

Protective Effect of Shenfu Injection on Vascular Endothelial Damage in a Porcine Model of Hemorrhagic Shock.

OBJECTIVE: To investigate the effects of Shenfu Injection (, SFI) on endothelial damage in a porcine model of hemorrhagic shock (HS). METHODS: After being bled to a mean arterial pressure of 40±3 mm Hg and held for 60 min, 32 pigs were treated with a venous injection of either shed blood (transfusion group), shed blood and saline (saline group), shed blood and SFI (SFI group) or without resuscitation (sham group). Venous blood samples were collected and analyzed at baseline and 0, 1, 2, 4, and 6 h after HS. Tumor necrosis factor-α (TNF-α), serum interleuking (IL)-6, and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM -1), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and Bcl-2, Bax, and caspase-3 proteins were determined by Western blot. RESULTS: The serum level of TNF-α in the SFI group was significantly lower than in the other groups at 0, 1, and 2 h after HS, while the level of IL-6 was lower at 4 and 6 h compared with the saline group (P<0.01 or P<0.05). The concentration of serum IL-10 was significantly higher in the SFI group than in the other groups at 0, 1, 4, and 6 h after HS (P<0.01). Western blot and immunohistochemistry of vascular tissue showed that the expression of caspase-3 was downregulated, and that of Bcl-2 and Bax was upregulated in the SFI group compared to other groups (P<0.05). CONCLUSION: SFI attenuated endothelial injury in the porcine model of HS by inhibiting cell apoptosis, suppressing the formation of proinflammatory cytokines, and reducing endothelial activation.

Shen-fu injection alleviates acute renal injury by reducing cytokine levels and modulating apoptosis in a porcine hemorrhagic shock model.

PURPOSE: Shen-fu injection (SFI) was used to intervene in the resuscitation of porcine hemorrhagic shock (HS) model to study its protective effects on acute kidney injury. METHODS: After 60 min of HS, 28 animals were randomly assigned into four groups. The groups were as follows: hemorrhagic shock group (HS); HS resuscitation with shed-blood group (HSR); HS resuscitation with shed-blood and SFI (1 mL·kg-1) group (HSR-SFI); and the sham operation group (Sham). The bloods were analyzed for serum creatinine (sCr), cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL). BAX, Bcl-2, and caspase-3 protein expressions by Western blot analysis and immunohistochemical staining. The renal tissues were removed and pathologic changes were observed. RESULTS: Mean aortic pressure (MAP) in HSR-SFI groups were higher than that in HSR groups after shock. At the 6th hour after shock, the urine volume per hour in the HSR-SFI groups was more than that in the HSR groups. The sCr, NGAL, CysC and cytokine levels of HSR-SFI groups were lower. The Bcl-2 expression was increased in the HSR-SFI groups. The BAX and caspase-3 expressions were reduced. The histopathologic score in the HSR-SFI was lower. CONCLUSIONS: SFI may reduce the risk of acute kidney injury (AKI) following hemorrhagic shock by attenuating systemic inflammatory responses, and regulating the expression of apoptosis-related proteins.

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

OBJECTIVE: To investigate whether Shenfu Injection (SFI, ) 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) mRNAs 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.

Shen-fu injection alleviates acute renal injury by reducing cytokine levels and modulating apoptosis in a porcine hemorrhagic shock model

ABSTRACT Purpose Shen-fu injection (SFI) was used to intervene in the resuscitation of porcine hemorrhagic shock (HS) model to study its protective effects on acute kidney injury. Methods After 60 min of HS, 28 animals were randomly assigned into four groups. The groups were as follows: hemorrhagic shock group (HS); HS resuscitation with shed-blood group (HSR); HS resuscitation with shed-blood and SFI (1 mL·kg-1) group (HSR-SFI); and the sham operation group (Sham). The bloods were analyzed for serum creatinine (sCr), cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL). BAX, Bcl-2, and caspase-3 protein expressions by Western blot analysis and immunohistochemical staining. The renal tissues were removed and pathologic changes were observed. Results Mean aortic pressure (MAP) in HSR-SFI groups were higher than that in HSR groups after shock. At the 6th hour after shock, the urine volume per hour in the HSR-SFI groups was more than that in the HSR groups. The sCr, NGAL, CysC and cytokine levels of HSR-SFI groups were lower. The Bcl-2 expression was increased in the HSR-SFI groups. The BAX and caspase-3 expressions were reduced. The histopathologic score in the HSR-SFI was lower. Conclusions SFI may reduce the risk of acute kidney injury (AKI) following hemorrhagic shock by attenuating systemic inflammatory responses, and regulating the expression of apoptosis-related proteins.

Effects of Shenfu Injection () on cerebral metabolism in a porcine model of cardiac arrest.

OBJECTIVE: To investigate the effects of Shenfu Injection (, SFI) on cerebral metabolism in a porcine model of cardiac arrest (CA). METHODS: Thirty 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. RESULTS: Compared 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. CONCLUSIONS: Sficould alleviate brain injury after CA, which may be associated with improving cerebral metabolism.

Effects of Shen-Fu Injection () 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 (, 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 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). RESULTS: Compared 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). CONCLUSIONS: SFI has signifificant effects in attenuating post-resuscitation immune dysfunction by modulating apoptosis of Treg in the spleen.

[Protective Effect of Shenfu Injection on Postresuscitation Lung Injury in a Porcine Model of As- physia-induced Cardiac Arrest].

Objective To observe the protective effect of Shenfu Injection ( SFI) on post-resusci- tation lung injury in a porcine model of asphyxia-induced cardiac arrest. Methods Thirty-four anaesthe- tized Wuzhi Mountain inbred miniature piglets of both sexes were subjected to asphyxia by intubation clip- ping, followed by standard cardiopulmonary resuscitation. Eighteen successfully resuscitated pigs [with recovery of return of spontaneous circulation ( ROSC) ] were divided into the SFI group and the normal saline (NS) group according to random digit table, 9 in each group. SFI at 0. 24 mg/min was intravenously pumped to piglets in the SFI group immediately from ROSC to 6 h after resuscitation, while NS at 0. 24 mg/min was intravenously pumped to piglets in the NS group immediately from ROSC to 6 h after resusci- tation. Oxygen metabolism, respiratory mechanics indices including oxygenation index (ΟI) , respiration index ( RI) , oxygen delivery ( DO2), oxygen consumption ( VO2), oxygen extraction ratio (Ο2 ER), PaCO2, lactic acid (LAC) were detected using blood gas analyzer at basic state, immediately after ROSC, 15 and 30 min, 1, 2, 4, and 6 h after ROSC. Dynamic lung compliance (Cdyn) , airway resistance (Raw), external vascular lung water index (EVLWI) , pulmonary vascular permeability index (PVPI) were monitored at each aforesaid time point. Activities of Na+-K +-ATPase and Ca² +-ATPase, contents of SOD and MDA, concentrations of TNF-α, IFN-γ, and IL-4 were determined using ELISA.IFN-γ/IL-4 ratio was calculated. Cell apoptosis was detected using TUNEL and apoptotic index (Al) calculated. Protein concentrations of Bcl-2 and Bax were detected using immunohistochemical assay, and Bax/Bcl-2 ratio calculated. Caspase-3 protein was quantitatively detected using Western blot. Results The survival rate was 88. 9% (8/9) in the SFI group and 66. 7% (6/9) in the NS group at 6 h after ROSC. The mean survival time was (5. 77 ±0. 71) h in the SFI group, longer than that in the NS group [ (4. 77 ±0. 59) h, P >0. 05]. Compared with the basic state, 01 and Cdyn obviously decreased immediately after ROSC (P <0. 05) ; RI, DO2, VΟ2, O2ER, Raw, EVLWI, PVPI, PaCO2, and LAC obviously increased immediately after ROSC (P<0. 05). All indices were recovered as time went by. Compared with the NS group, ΟI, Cdyn, DO2, VΟ2, and Ο2 ER at each time points after ROSC were significantly higher in the SFI group than in the NS group (P <0. 05, P <0. 01); RI, Raw, EVLWI, PVPI, PaCO2, and LAC were significantly lower in the SFI group than in the NS group (P <0. 05, P <0. 01 ). Compared with the NS group, activities of Na'-K '-AT- Pase and Ca² +-ATPase, contents of SOD, level of IFN-γ, IFN-γ/IL-4 ratio, concentrations of Bcl-2 in- creased more; MDA, TNF-α, IL-4 level, Al, Bax/Bcl-2 ratio, Caspase-3 protein level decreased more (P <0. 05, P <0. 01). Conclusion SFI could improve cell energy metabolism, enhance antioxidant ca- pacity of cells, reduce the release of inflammatory mediators, regulate the Thl/Th2 balance, and attenu- ate cell apoptosis of lung tissue, thereby protecting post-resuscitation lung injury.

Comparison of Shenfu Injection () and epinephrine on catecholamine levels in a porcine model of prolonged cardiac arrest.

OBJECTIVE: To compare the effects of Shenfu Injection (SFI) and epinephrine (EPI) on catecholamine levels in a porcine model of prolonged cardiac arrest (CA). METHODS: After 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. RESULTS: The 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). CONCLUSIONS: SFI 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.

Shen-Fu Injection () alleviates post-resuscitation myocardial dysfunction by up-regulating expression of sarcoplasmic reticulum Ca(2+)-ATPase.

OBJECTIVE: To compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction. METHODS: Ventricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 µg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of ß1-adrenoceptor (AR) and SERCA 2a were determined. RESULTS: Cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of ß1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01). CONCLUSIONS: The administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression.

Effects of Chinese medicine shen-fu injection on the expression of inflammatory cytokines and complements during post-resuscitation immune dysfunction in a porcine model.

OBJECTIVE: To investigate the action of Shen-Fu Injection (SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest (CA) and resuscitation. METHODS: Thirty pigs were randomly divided into the sham (n=6) and 3 returns of spontaneous circulation (ROSC) groups (n=24). After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs of the ROSC groups were randomized into three groups (n=8 per group), which received central venous injection of SFI (SFI group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 12, and 24 h after ROSC. RESULTS: Serum concentrations of specific activation markers of the complement system C3, C4 and C5b-9 were increased during cardiopulmonary resuscitation through 24 h after ROSC. There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA. Compared with the EP and SA groups, SFI treatment reduced the proinflammatory cytokines levels of interleukin (IL)-6, IL-8 and tumor necrosis factor α (TNF-α, P<0.05), and increased the anti-inflammatory cytokine levels of IL-4 and IL-10 (P<0.05). Further, SFI treatment decreased the values of C3, C4 and C5b-9 compared with the EP and SA groups. CONCLUSIONS: SFI, derived from the ancient Chinese medicine, has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels. The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.

Effect of Shen-Fu Injection Pretreatment to Myocardial Metabolism During Untreated Ventricular Fibrillation in a Porcine Model.

BACKGROUND: Shen-Fu injection (SFI) can attenuate ischemia-reperfusion injury, protect cardiac function, and improve microcirculation during cardiopulmonary resuscitation. We hypothesized that SFI may also have an influence on myocardial metabolism during ventricular fibrillation (VF). In this study, we used SFI pretreatment prior to VF to discuss the changes of myocardial metabolism and catecholamine (CA) levels during untreated VF, trying to provide new evidence to the protection of SFI to myocardium. METHODS: Twenty-four pigs were divided into three groups: Saline group (SA group), SFI group, and SHAM operation group (SHAM group). Thirty minutes prior to the induction of VF, the SFI group received 0.24 mg/ml SFI through an intravenous injection; the SA group received an equal amount of sodium chloride solution. The interstitial fluid from the left ventricle (LV) wall was collected through the microdialysis tubes during VF. Adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Na + -K + -ATPase and Ca2 + -ATPase enzyme activities were measured after untreated VF. Peak-to-trough VF amplitude and median frequency were analyzed for each of these 5-s intervals. RESULTS: The levels of glucose and glutamate were lower after VF in both the SA and SFI groups, compared with baseline, and the levels in the SFI group were higher than those in the SA group. Compared with baseline, the levels of lactate and the lactate/pyruvate ratio increased after VF in both SA and SFI groups, and the levels in the SFI group were lower than those in the SA group. In both the SA and SFI groups, the levels of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATP, ADP, and phosphocreatine in the SFI group was higher than those in the SA group. The activity of LV Na + -K + -ATPase was significantly higher in the SFI group than in the SA group. Amplitude mean spectrum area (AMSA) was significantly lower in the SA and SFI groups at 8- and 12-min compared with 4-min. The AMSA in the SFI group was higher than that in the SA group at each time point during untreated VF. CONCLUSIONS: SFI pretreatment can improve myocardial metabolism and reduce energy exhaustion during VF, and it does not aggravate the excessive secretion of endogenous CAs.

[Transurethral resection of the prostate combined with 2-micron continuous-wave laser vaporesection for benign prostatic hyperplasia with the prostate volume > 80 ml].

OBJECTIVE: To sum up the clinical experience in the management of benign prostatic hyperplasia (BPH) with the prostate weighing over 80 ml by transurethral resection of the prostate (TURP) combined with 2 µm continuous-wave laser vaporesection (LVR). METHODS: We retrospectively analyzed the clinical effects of TURP combined with 2 µm LVR in the treatment of 46 cases of BPH with the prostate volume > 80 ml. RESULTS: All the operations were successfully accomplished. The operation time and intraoperative blood loss were (112.0 ± 20.0) min (range 86-176 min) and (77.9 ± 25.9) ml (range 50-200 ml), respectively. The catheters were withdrawn at 7 days after surgery. Transient urinary incontinence occurred in 6 cases and secondary hemorrhage was found in 2 postoperatively. Six-month follow-up revealed no urethral stricture or other complications. Compared with the baseline, the international prostate symptom score (IPSS) was significantly decreased at 6 months after operation (26.3 ± 1.8 vs 11.6 ± 1.7, P <0.05), and so were the quality of life (QOL) score (5.3 ± 0.7 vs 1.3 ± 1.1, P <0.05) and post-void residual urine (PVR) ([115.5 ± 55.6] ml vs [19.9 ± 11.6] ml, P <0.05). However, the maximum urinary flow rate (Qmax) was remarkably increased from (4.1 ± 2.6) ml/s to (16.2 ± 1.7) ml/s (P <0.05). CONCLUSION: TURP combined with 2 µm LVR is safe and effective for the treatment of BPH with the prostate volume >80 ml.

Neuroprotective effect of Shenfu Injection () following cardiac arrest in pig correlates with improved mitochondrial function and cerebral glucose uptake.

OBJECTIVE: To test whether Shenfu Injection (, SFI) might attenuate the impact of cerebral energy dysfunction after resuscitation in a pig model of cardiac arrest (CA). METHODS: Thirty-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. RESULTS: Compared 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). CONCLUSION: SFI treatment after resuscitation has significant neuroprotective effects against disruption of cerebral energy metabolism from CA by improving glucose uptake and by normalizing mitochondrial function.

Therapeutic effects of Shenfu Injection on post-cardiac arrest syndrome.

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.

Advances and challenges in screening traditional Chinese anti-aging materia medica.

To provide a better service for senior health care, we summarized screening studies of traditional Chinese anti-aging materia medica (TCAM). We collected and analyzed literature of TCAM screening studies using the lifespan test and animal models of aging from 1984 to 2012. We found 26 screening methods for TCAM, and 153 single herbs or active ingredients of TCAM that have been screened out during the past 28 years. The cell lifespan test, the fruit fly lifespan test, and D-galactose aging model were the most widely used and intensively studied screening methods. However, the method for establishing the D-galactose aging model needs to be standardized, and the D-galactose aging model cannot completely be a substitute for the normal aging mouse model. Great success has been achieved in screening studies in TCAM. To further improve screening studies in TCAM, we suggest that the D-galactose aging model be incorporated into the lifespan test in the New Drugs of Traditional Chinese Medicine Research Guide.

Shen-Fu injection reduces impaired myocardial ß-adrenergic receptor signaling after cardiopulmonary resuscitation.

BACKGROUND: Post-resuscitation myocardial dysfunction has been implicated as a major cause of fatal outcome in patients who survive initially successful cardiopulmonary resuscitation (CPR). In our previous study, we found that impaired myocardial ß-adrenergic receptor (AR) signaling is a key mechanism in post-resuscitation myocardial dysfunction and Shen-Fu injection (SFI) can attenuate post-resuscitation myocardial dysfunction. However, whether SFI can prevent impaired post-resuscitation myocardial ß-AR signaling is not yet known. In this study, we investigated the effect of SFI on impaired myocardial ß-AR signaling occurring post-resuscitation in a porcine model of cardiac arrest. METHODS: Ventricular fibrillation was induced electrically in anesthetized male landrace domestic pigs. After 4 minutes of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated. Sixteen successfully resuscitated pigs were randomized to receive a continuous infusion of either SFI (0.5 ml/min; n = 8) or saline (placebo; n = 8) for 6 hours, beginning 15 minutes after the return of spontaneous circulation (ROSC). Hemodynamic and echocardiographic data were recorded. ß-AR signaling was assessed at 6 hours after the intervention by measuring myocardial adenylate cyclase activity, ß-AR density and ß-AR kinase expression. RESULTS: Treatment with SFI produced better maximum rate of left ventricular pressure increase (dp/dt(max)) and maximum rate of left ventricular pressure decline (-dp/dt(max)), cardiac output, and ejection fraction after ROSC. SFI treatment was also associated with lower myocardial ß-adrenergic receptor kinase expression, whereas basal and isoproterenol-stimulated adenylate cyclase activity and the total ß-AR density were significantly increased in the SFI group when compared with the placebo group. CONCLUSION: SFI attenuated post-resuscitation myocardial dysfunction by preventing impaired myocardial ß-AR signaling after CPR.

Shen-fu injection attenuates postresuscitation lung injury in a porcine model of cardiac arrest.

OBJECTIVE: To investigate the effects of Shen-Fu injection (SFI) on postresuscitation lung injury in a porcine model of cardiac arrest. METHODS: Twenty-four anaesthetised male Landrace pigs were subjected to 4 min of untreated ventricular fibrillation (VF), followed by standard cardiopulmonary resuscitation. Sixteen successfully resuscitated pigs were randomised into two groups (eight pigs per group); one group received an SFI infusion and the other group received a normal saline infusion, at an infusion rate of 0.24 mg/min from 15 min after the return of spontaneous circulation (ROSC) until 6h after ROSC. RESULTS: Oxygenation index, respiratory index, oxygen delivery, oxygen consumption, oxygen extraction, dynamic lung compliance, airway resistance, external vascular lung water index, and pulmonary vascular permeability index at 15 min, 30 min, 1h, 2h, 4h, and 6h after ROSC were all worse than baseline in the saline group, and were all better in the SFI group than in the saline group. The pulmonary protective effects of SFI were further confirmed by histopathological and ultrastructural observations of lung tissue. SFI infusion resulted in lower apoptosis index, caspase-3 protein expression, and malondialdehyde content of lung tissue after ROSC, and increased Bcl-2 protein expression and superoxide dismutase, Na+ -K+ -ATPase, and Ca2+ -ATPase activity compared with the saline group. CONCLUSION: Shen-Fu injection can attenuate postresuscitation lung injury through suppression of lung cell apoptosis and improvement of energy metabolism and antioxidant capacity.

Shen-fu injection attenuates postresuscitation myocardial dysfunction in a porcine model of cardiac arrest.

To investigate the effect of Shen-Fu injection (SFI) for the management of postresuscitation myocardial dysfunction in a porcine model of cardiac arrest. Ventricular fibrillation was induced electrically in anesthetized domestic swine. After 4 min of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated. Sixteen successfully resuscitated pigs were randomized to receive a continuous infusion of either SFI (0.24 mg/min) or saline placebo for 6 h, beginning 15 min after return of spontaneous circulation (ROSC). The SFI treatment produced better left ventricular +dP/dtmax, -dP/dtmax, cardiac output, and ejection fraction after ROSC. The SFI treatment also produced lower serum cardiac troponin I, lactate levels, and left ventricle malondialdehyde content after ROSC, whereas left ventricle superoxide dismutase, Na-K-ATPase, and Ca-ATPase activity were significantly increased in the SFI group when compared with saline group. The cardioprotective effect of SFI was further confirmed by myocardial ultrastructure examination. Shen-Fu injection can attenuate postresuscitation myocardial dysfunction through beneficial effects on energy metabolism and remarkable antioxidant capacity.

[The role of extracellular signal-regulated kinase in induction of apoptosis with salvia miltiorrhiza monomer IH764-3 in hepatic stellate cells].

OBJECTIVE: To explore the effect of Salvia miltiorrhiza monomer IH764-3 on apoptosis in hydrogen peroxide (H2O2)-stimulated hepatic stellate cells (HSCs). METHODS: HSCs were cultured in medium with different IH764-3 doses (10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L) and without IH764-3. Direct cell count, 3H-thymidine incorporation, Annexin-V/Propidium Iodide double-labeled flow cytometry, TUNEL and transmission electron microscopy were employed to estimate the influence of IH764-3 on proliferation and apoptosis of HSCs. The expression of extracellular signal-regulated kinase 1 (ERK1) mRNA and protein in HSCs were detected using RT-PCR and Western blot respectively. RESULTS: It was showed that H2O2 could promote HSC proliferation. In contrast, IH764-3 at concentrations of 10 mg/L, 20 mg/L, 30 mg/L and 40 mg/L inhibited its proliferation. The inhibition rates were 7.13%, 28.36%, 53.80% and 73.10% (P < 0.01). And the inhibition rates of IH764-3 at concentrations of 30 mg/L at 12 h, 24 h and 48 h were 22.24%, 40.51% and 61.65%. Furthermore, IH764-3 could also induce the HSC apoptosis in dose-dependent an dtime-dependent manners (P < 0.01). In addition, after exposed of HSCs to IH764-3 for 24 h, ERK production decreased and ERK1 mRNA was down-regulated earlier about 2 h after exposure to IH764-3. CONCLUSION: IH764-3 may inhibit the proliferation and induce apoptosis of HSCs in both dose-dependent and time-dependent manners, which may be related to down-regulation of ERK expression.