Background Epinephrine 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...Background Epinephrine 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.Methods Ventricular 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.Results SFI 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.Conclusions SFI 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.展开更多
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 ...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 ventrictdar 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 myocardiurn. 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 levers of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATE ADE and phosphocreatine in the SF1 group was higher than those in the SA group. The activity ofLV 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.展开更多
Objective: To investigate the hemodynamic effect of Shen-Fu Injection(参附注射液, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output(PICCO). Method...Objective: To investigate the hemodynamic effect of Shen-Fu Injection(参附注射液, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output(PICCO). Methods: All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1 st, 2014 to December 31 th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group(33 cases) and control group(32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. Results: The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h(P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group(P<0.05), including cardiac index(CI), global end diastolic volume index(GEDI), mean arterial pressure(MAP) and heart rate(HR). In addition, there was no significant change of extra-vascular lung water index between the two groups(P>0.05). Conclusion: SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.展开更多
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 ...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 β-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 β-AR signaling is not yet known. In this study, we investigated the effect of SFI on impaired myocardial β-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. β-AR signaling was assessed at 6 hours after the intervention by measuring myocardial adenylate cyclase activity, β-AR density and β-AR kinase expression. Results Treatment with SFI produced better maximum rate of left ventricular pressure increase （dp/dtmax） and maximum rate of left ventricular pressure decline （-dp/dtmax）, cardiac output, and ejection fraction after ROSC. SFI treatment was also associated with lower myocardial β-adrenergic receptor kinase expression, whereas basal and isoproterenol- stimulated adenylate cyclase activity and the total β-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 β-AR signaling after CPR.展开更多
Objective： To compare the effect of Shen-Fu Injection （SFI） and epinephrine on the expression of sarcoplasmic reticulum Ca2. ATPase 2a （SERCA2a） in a pig model with post-resuscitation myocardial dysfunction. Meth...Objective： To compare the effect of Shen-Fu Injection （SFI） and epinephrine on the expression of sarcoplasmic reticulum Ca2. 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 t~ g/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 rain 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 13 1-adrenoceptor （AR） and SERCA 2a were determined. Results： Cardiac output, left ventricular dp/dtr,~x and negative dp/dtm^x were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of 13 1-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.展开更多
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...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.展开更多
基金This research was supported by a grant from the Beijing Natural Science Foundation
文摘Background Epinephrine 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.Methods Ventricular 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.Results SFI 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.Conclusions SFI 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.
基金This work was supported b-y grants from the National Natural Science Foundation of China （No. 81372025） and the Beijing Natural Science Foundation （No. 7132092）.
文摘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 ventrictdar 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 myocardiurn. 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 levers of dopamine, norepinephrine, and epinephrine increased significantly. There were no statistical differences between the two groups. The content of ATE ADE and phosphocreatine in the SF1 group was higher than those in the SA group. The activity ofLV 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.
基金Supported by Science and Technology Development Plan of Shandong Province(No.2012YD19011)Medical and Health Technology Development Plan of Shandong Province(No.2013WS0250)+2 种基金National Natural Science Foundation of China(No.81503543)Traditional Chinese Medicine Science and Technology Development Plan of Shandong Province(No.2011-095 and 2013-080)Key Development Program of Shandong Province,China(No.2016GSF202029)
文摘Objective: To investigate the hemodynamic effect of Shen-Fu Injection(参附注射液, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output(PICCO). Methods: All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1 st, 2014 to December 31 th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group(33 cases) and control group(32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. Results: The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h(P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group(P<0.05), including cardiac index(CI), global end diastolic volume index(GEDI), mean arterial pressure(MAP) and heart rate(HR). In addition, there was no significant change of extra-vascular lung water index between the two groups(P>0.05). Conclusion: SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.
文摘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 β-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 β-AR signaling is not yet known. In this study, we investigated the effect of SFI on impaired myocardial β-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. β-AR signaling was assessed at 6 hours after the intervention by measuring myocardial adenylate cyclase activity, β-AR density and β-AR kinase expression. Results Treatment with SFI produced better maximum rate of left ventricular pressure increase （dp/dtmax） and maximum rate of left ventricular pressure decline （-dp/dtmax）, cardiac output, and ejection fraction after ROSC. SFI treatment was also associated with lower myocardial β-adrenergic receptor kinase expression, whereas basal and isoproterenol- stimulated adenylate cyclase activity and the total β-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 β-AR signaling after CPR.
文摘Objective： To compare the effect of Shen-Fu Injection （SFI） and epinephrine on the expression of sarcoplasmic reticulum Ca2. 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 t~ g/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 rain 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 13 1-adrenoceptor （AR） and SERCA 2a were determined. Results： Cardiac output, left ventricular dp/dtr,~x and negative dp/dtm^x were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of 13 1-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.
基金Supported by the National Natural Science Foundation of China(No.81372025)Basic and Clinical Research Cooperation Project of Capital Medical University(No.15JL42)Beijing Municipal Administration of Hospitals Incubating Program(No.Px2016022)
文摘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.
