High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.

Differential Impact of Biologic Therapy on Heart Function Biomarkers in Rheumatoid Arthritis Patients: Observational Study on Etanercept, Adalimumab, and Tocilizumab.

BACKGROUND: Rheumatoid arthritis (RA) represents the most frequent form of inflammatory arthritis, affecting approximately 1% of the population worldwide. The introduction of novel therapeutic strategies targeting proinflammatory cytokines (TNF-α and interleukin-6) revolutionized the treatment of RA. This kind of treatment, although effective in a substantial portion of patients, may potentially cause many side effects. Among them, cardiovascular safety is one of the main concerns. OBJECTIVES: In the present study, we investigated the impact of treatment with anti-TNF-α and anti-IL-6 agents on heart function and levels of heart function biomarkers. METHODS: To measure this, we used cardiac function biomarkers, such as NT-pro Brain Natriuretic Peptide, mid regional pro-Atrial Natriuretic Peptide, Galectin-3, and Heart-Type Fatty Acid-Binding Protein and compared them to patients treated with methotrexate as well as healthy controls. RESULTS: Patients treated with biologics were characterized by low disease activity or were in remission. The disease activity in these groups was significantly lower than in the methotrexate group. All patients recruited for the study were characterized by normal heart function measured using echocardiography (EF>50%). With the exception of MR-proANP between tocilizumab and adalimumab (median: 1.01 vs. 0.49 nmol/L, p<0.05), we failed to observe any significant differences in biomarkers levels between groups treated with biologics. Contrary to this, patients on MTX showed higher NT-proBNP levels compared to adalimumab and healthy controls (p<0.05 for both). Striking differences have been shown in regard to H-FABP. The levels of these biomarkers were elevated in all biologics and the methotrexate group compared to healthy controls. CONCLUSION: As this biomarker reflects potential heart injury, we suggest that heart damage proceeds in a continuous manner in RA patients despite effective treatment and attainment of remission/low disease activity. This finding, however, should be verified in a larger cohort of RA patients to ascertain if the routine assessment of H-FABP may be useful for the detection of patients with RA who are at risk of development of heart damage.

High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study.

BACKGROUND: Cardiac injury is common and associated with poor clinical outcomes in COVID-19. Data are lacking whether high-dose intravenous vitamin C (HIVC) could help to ameliorate myocardial injury in the pandemic. METHODS: The retrospective cohort study included consecutive severe and critically ill COVID-19 patients with cardiac injury receiving symptomatic supportive treatments alone or together with HIVC. Troponin I and inflammatory markers were collected at admission and day 21 during hospitalization from the electronic medical records. RESULTS: The patients (n = 113) were categorized into the ameliorated cardiac injury (ACI) group (n = 70) and the non-ameliorated cardiac injury (NACI) group (n = 43). Overall, fifty-one (45.1%) patients were administered with HIVC, the percentages of patients with HIVC were higher in the ACI group than those in the NACI group. Logistic regression analysis revealed that HIVC was independently associated with the improvement of myocardial injury. Further analysis showed that inflammatory markers levels significantly decreased at day 21 during hospitalization in patients with HIVC therapy compared to those administered with symptomatic supportive treatments alone. Meanwhile, similar results were also observed regarding changes in inflammatory markers levels from baseline to day 21 during hospitalization in the patients treated with HIVC. CONCLUSIONS: HIVC can ameliorate cardiac injury through alleviating hyperinflammation in severe and critically ill patients with COVID-19.

Ameliorative Effect of Dangguibuxue Decoction against Cyclophosphamide-Induced Heart Injury in Mice.

Dangguibuxue decoction (DBD), a kind of Chinese herbal medicine, has been widely used to treat blood deficiency disease in China. In this experiment, we studied the effects of the Dangguibuxue decoction (DBD) on the myocardial injury induced by cyclophosphamide in mice. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and lactic dehydrogenase (LDH) in serum were detected by commercial kits. Total white blood cell (WBCs), platelets, and cytokines pathological changes of heart tissue were also examined. In addition, the protein levels of the NF-кB pathway were detected to reveal its mechanism. The results showed that DBD significantly decreased the levels of ALT, AST, CK, and LDH and increased WBCs in CTX-induced mice. In addition, DBD significantly alleviated pathological changes of heart tissue. DBD significantly reduced the protein expressions of NF-кB signaling pathway. In summary, DBD can be considered an effective drug to alleviate CTX-induced heart damage in mice.

Protective effect of berberine on aconite­induced myocardial injury and the associated mechanisms.

Aconitum plants, which have analgesic, diuretic and anti­inflammatory effects, have been widely used to treat various types of disease. However, the apparent toxicity of Aconitum­derived agents, particularly in the cardiovascular system, has largely limited their clinical use. Thus, the present study investigated whether berberine (Ber), an isoquinoline alkaloid, may reduce myocardial injury induced by aconitine (AC) in rats and the underlying mechanisms. Rats (n=40) were randomly divided into four groups: Control, Chuan­wu and Chuan­wu + Ber (8 and 16 mg/kg doses). Electrocardiograms (ECG) of the rats were recorded and serum biomarkers of cardiac function [lactate dehydrogenase (LDH), creatine kinase (CK) and CK­MB] were assayed. Histopathological changes were assessed using myocardial tissue sectioning and hematoxylin and eosin staining. Additionally, the effects of Ber on AC­induced arrhythmias in rats were observed. The changes in ECG following AC perfusion were observed, and the types and onset time of arrhythmias were analyzed. Furthermore, the effects of Ber and AC on papillary muscle action potentials were observed. The results suggested that Ber ameliorated myocardial injury induced by Chuan­wu, which was indicated by reduced arrhythmias and decreased LDH, CK and CK­MB levels in serum. Furthermore, histological damage, including dilation of small veins and congestion, was also markedly attenuated by Ber. In addition, the occurrence of arrhythmias was significantly delayed, and the dosage of AC required to induce arrhythmias was also increased by Ber pretreatment. Additionally, AC­induced changes in action potential amplitude, duration of 30% repolarization and duration of 90% repolarization in the papillary muscle were attenuated by Ber. All of these results indicate that Ber had a preventive effect on acute myocardial injury induced by Chuan­wu and arrhythmias caused by AC, which may be associated with the inhibition of delayed depolarization and triggered activity caused by AC. Thus, combination treatment of Ber with Aconitum plants may be a novel strategy to prevent AC­induced myocardial injury in clinical practice.

[The protective effects of Haematococcus pluvialis on the exercise-induced myocardial injury in rat].

OBJECTIVE: To study the protective effects of Haematococcus pluvialis (H. pluvialis) on myocardial injury of rats induced by endurance and intensive exercise. METHODS: The model was based on intensive endurance training. Sixty-five male aged 42 days Wistar rats were randomly divided into 5 groups:control group (C group), general training group (M group), low dose H. pluvialis + training group (HM I group), middle dose H. Pluvialis + training group (HM Ⅱ group), high dose H. pluvialis + training group (HM Ⅲ group). Each group included 12 rats, and the rats were assigned to go on a 42-day swimming training regime. Professional gavage were taken daily. The rats in HM I, HM Ⅱ and HM Ⅲ group were treated with H. pluvialis at the doses of 0.067,0.133 and 0.4 g/kg by ig at 5 ml/kg and the normal saline were given to other groups. After a 42-day swimming training regime, myocardial injury markers such as serum alanine aminotransferase (ALT), myocardial superoxide dismutase(SOD) and malondialdehyde (MDA) were detected, the biochemical indexes such as serum and myocardial endothelin (ET) and calcitonin gene related peptide (CGRP)were detected. RESULTS: Serum ALT, lactate dehydrogenase(LDH), creatine kinase(CK), a-hydroxybutyrate dehydrogenase(a-HBDH), ET, myocardial MDA and ET in M group were significantly higher than those in C group (P<0.05 or P<0.01). The myocardial SOD activity and the myocardial and serum CGRP in M group were significantly lower than those in C group(P<0.05 or P<0.01). The contents of serum ALT, LDH and CK in HM groups were lower than those in the M group but there was no significant difference between the two groups. Compared with M group, H. pluvialis could decrease the levels of serum a-HBDH, ET and myocardial ET in a dose-dependent manner (P<0.05 or P<0.01). The above mentioned three parameters in HM Ⅲ group were lower than those in HM I group (P<0.05). H. pluvialis could decrease the levels of myocardial MDA and increase the levels of myocardial SOD activity and serum or myocardial CGRP in a dose-dependent manner (P<0.05 or P<0.01). CONCLUSIONS: The different doses of H.pluvialis can effectively reduce the free radicals caused by endurance and intensive training and enhance the immune function. Meanwhile H.pluvialis is able to guarantee the relative balance in ET an CGRP`s concentration. Therefore, the myocardial lipid peroxidation and myocardial injury are encumbered. Additionaly, high dose of H. pluvialis is proven to be the most effective.

Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: A biochemical, histopathological, and immunohistochemical study.

Cisplatin (cis-diamminedichloroplatinum, CDDP) is an effective DNA alkylating agent used in the treatment of different types of tumors; however, its clinical use is associated with hepato-cardiotoxicity. The current study was designed to assess the potential protective effect of parsley oil (PO) against CDDP-induced hepato-cardiotoxicity. For this purpose, 25 adult male rats were assigned into five groups, each containing five animals. Group I (control) was administered saline solution. Group II was administered PO at a dosage of 0.42ml/kg BW. Group III were administered CDDP at a dosage of 5mg/kg BW. Group IV was administered PO in addition to CDDP. Group V was administered saline solution in addition to CDDP, after which they were administered PO for five days. Oral administration of either saline solution or PO was performed each day for 10days, while administration of CDDP was via a single intraperitoneal injection five days following the commencement of the experiment. The recorded results revealed that CDDP induced obvious hepatic and cardiac injuries that were indicated by biochemical, histopathological, and immunohistochemical alterations, including elevation of serum hepatic and cardiac injury markers as well as proinflammatory cytokines. Moreover, CDDP induced an increase in the level of hepatic and cardiac injury biomarkers, decreases in the activities of antioxidant enzymes, a decrease in GSH concentration, and an increase in MDA concentration. CDDP also induced histopathological hepatocellular and myocardial changes, and overexpression of p53 and COX-2 in hepatic and cardiac tissues. Administration of PO either as a preventative medicine or as treatment significantly improved all the observed deleterious effects induced by CDDP in rat liver and heart. Thus, it may be concluded that PO, with its antioxidant, anti-inflammatory, and antiapoptotic activities, can potentially be used in the treatment of CDDP-induced hepatic and cardiac injuries.

Delonix regia Leaf Extract (DRLE): A Potential Therapeutic Agent for Cardioprotection.

Delonix regia (Boj. Ex. Hook) is a flowering plant in the pea family found in tropical areas and its leaves are used informally to treat diseases in folk medicine. However, the cardioprotective effects in this plant are still unclear. In this study, we found that the Delonix regia leaf extract (DRLE) (400 mg/kg/d) can reduce the mortality rate in an isoproterenol (ISO)-induced heart injury and hypertrophy mouse model. Decreased serum levels of creatine phosphokinase, LDH, GOT, TNF-alpha and increased nitric oxide levels were found in DRLE-treated ISO-injured mice. In the in vitro study, the porcine coronary artery exhibited vasodilation effect induced by DRLE in a dose-dependent manner. In the DRLE toxic test, overdose of DRLE showed the high safety in normal mice and may have the ability to remove the metabolic wastes in blood. In conclusion, we demonstrated for the first time that DRLE has the cardioprotective effects by activating the vasodilation through NO pathway and preventing the myocyte injury via inhibition of TNF-alpha pathway. We suggest that DRLE may act as a promising novel herbal medicine for cardioprotection.

Protective effect of Xuebijing injection on myocardial injury in patients with sepsis: a randomized clinical trial.

OBJECTIVE: To investigate the protective effect and possible mechanism of Xuebijing Injection on myocardial injury in patients with sepsis, and to evaluate its prognostic implications. METHODS: Patients with septic myocardial injury were recruited, and were randomly divided into two groups: treatment group and control group. All patients in two groups received conventional cluster treatment, the patients in treatment group additional received Xuebijing injection dissolved in 0.9% sodium chloride injection, and the patients in control group received the same amount of 0.9% sodium chloride injection. At the beginning of treatment and 3, 7 and 10-day after treatment, laboratory indicators of cardiac troponin Ⅰ (cTnI), N-terminal proB-type natriuretic peptide (NT-proBNP) and procalcitonin (PCT) were respectively tested in venous blood. The patient's length of stay in Intensive Care Unit (ICU) and the mortality in 28 days were recorded. RESULTS: At 3, 7 and 10-day after treatment, the improvements of cTnI, NT-proBNP and PCT in treatment group were better than those in control group, and the differences were statistically significant (P < 0.05). The mortality of treatment group in 28 days was not significantly different from that of control group (P > 0.05). The ICU length of stay of treatment group was shorter than that of control group (P > 0.05). CONCLUSION: Xuebijing injection could improve the levels of cTnI, NT-proBNP and PCT in patients with septic myocardial injury .and it had a protective effect on myocardial injury.

Blueberry Anthocyanins-Enriched Extracts Attenuate Cyclophosphamide-Induced Cardiac Injury.

We sought to explore the effect of blueberry anthocyanins-enriched extracts (BAE) on cyclophosphamide (CTX)-induced cardiac injury. The rats were divided randomly into five groups including normal control, CTX 100 mg/kg, BAE 80mg/kg, CTX+BAE 20mg/kg and CTX+BAE 80mg/kg groups. The rats in the three BAE-treated groups were administered BAE for four weeks. Seven days after BAE administration, rats in CTX group and two BAE-treated groups were intraperitoneally injected with a single dose of 100 mg/kg CTX. Cardiac injury was assessed using physiological parameters, Echo, morphological staining, real-time PCR and western blot. In addition, cardiotoxicity indices, inflammatory cytokines expression and oxidative stress markers were also detected. Four weeks 20mg/kg and 80mg/kg dose of BAE treatment following CTX exposure attenuated mean arterial blood pressure, heart rate and activities of heart enzymes, improved cardiac dysfunction, left ventricular hypertrophy and fibrosis. Importantly, BAE also attenuated CTX-induced LV leukocyte infiltration and inflammatory cytokines expression, ameliorated oxidative stress as well as cardiomyocyte apoptosis. In conclusion, BAE attenuated the CTX-induced cardiac injury and the protective mechanisms were related closely to the anti-inflammatory, antioxidant and anti-inflammatory characteristics of BAE.

Protective effects of piperine against copper-ascorbate induced toxic injury to goat cardiac mitochondria in vitro.

Piperine, the main alkaloid of black pepper, Piper nigrum Linn., is an important Indian spice used in traditional food and medicine in India. In the present study, we investigated the antioxidant activities of piperine against copper-ascorbate induced toxic injury to mitochondria obtained from a goat heart, in vitro. Incubation of isolated cardiac mitochondria with copper-ascorbate resulted in elevated levels of lipid peroxidation and protein carbonylation of the mitochondrial membrane, a reduced level of mitochondrial GSH and altered status of antioxidant enzymes as well as decreased activities of pyruvate dehydrogenase and the Kreb's cycle enzymes, altered mitochondrial morphology, mitochondrial swelling, di-tyrosine level and mitochondrial DNA damage. All these changes were found to be ameliorated when the cardiac mitochondria were co-incubated with copper-ascorbate and piperine, in vitro. Piperine, in our in vitro experiments, was found to scavenge hydrogen peroxide, superoxide anion free radicals, hydroxyl radicals and DPPH radicals, in a chemically defined system, indicating that this compound may provide protection to cardiac mitochondria against copper-ascorbate induced toxic injury through its antioxidant activities. The results of this study suggest that piperine may be considered as a future therapeutic antioxidant and may be used singly or as a co-therapeutic in the treatment of diseases associated with mitochondrial oxidative stress.

Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis.

AIM: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. METHODS: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to (1)H-NMR-based metabolomic analysis. RESULTS: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. CONCLUSION: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The (1)H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.

Oxymatrine protects against myocardial injury via inhibition of JAK2/STAT3 signaling in rat septic shock.

Oxymatrine (OMT), an alkaloid extracted from Sophora japonica (kushen), is used to treat inflammatory diseases and various types of cancer in traditional Chinese medicine. However, the cellular and molecular mechanisms underlying the anti­inflammatory activity of OMT remain poorly understood. The present study explored the protective effect of OMT on myocardial injury in rats with septic shock by inhibiting the activation of the janus kinase­signal transducer and activator of transcription (JAK/STAT) signaling pathway. OMT treatment was found to significantly inhibit the activation of JAK2 and STAT3 in myocardial tissue. It also attenuated the expression of pro­inflammatory cytokines, including interleukin­1ß and tumor necrosis factor­α. In addition, OMT exhibited anti­inflammatory properties as heart function and myocardial contractility was improved and pathological and ultrastructural injury was prevented in myocardial tissue induced by septic shock. The results indicate that OMT exhibits substantial therapeutic potential for the treatment of septic shock­induced myocardial injury through inhibition of the JAK2/STAT3 signaling pathway.

Antioxidant and antiapoptotic effects of proanthocyanidin and ginkgo biloba extract against doxorubicin-induced cardiac injury in rats.

Grape seed proanthocyanidins (GSPE) and ginkgo biloba extract (EGb761) are considered to have protective effects against several diseases. The cardiotoxicity of doxorubicin (DOX) has been reported to be associated with oxidative damage. This study was conducted to evaluate the cardioprotective effects of GSPE and EGb761 against DOX-induced heart injury in rats. DOX was administered as a single i.p. dose (20 mg kg(-1)) to adult male rats. DOX-intoxicated rats were orally administered GSPE (200 mg kg(-1) day(-1)) or EGb761 (100 mg kg(-1) day(-1)) for 15 consecutive days, starting 10 days prior DOX injection. DOX-induced cardiotoxicity was evidenced by a significant increase in serum aspartate transaminase (AST), creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), total cholesterol (TC) and triglyceride (TG) activities and levels. Increased oxidative damage was expressed by the depletion of cardiac reduced glutathione (GSH), elevation of cardiac total antioxidant (TAO) level and accumulation of the lipid peroxidation product, malondialdehyde (MDA). Significant rises in cardiac tumour necrosis factor-alpha (TNF-α) and caspase-3 levels were noticed in DOX-intoxicated rats. These changes were ameliorated in the GSPE and EGb761-treated groups. Histopathological analysis confirmed the cardioprotective effects of GSPE and EGb761. In conclusion, GSPE and EGb761 mediate their protective effect against DOX-induced cardiac injury through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury.

The present study was designed to elucidate the outcome of subchronic co-administration of black tea and nicotine on cardiovascular performance and whether these substances could modulate the isoproterenol-induced cardiac injury. Animal groups were control, black tea, nicotine and black tea plus nicotine. Test groups received nicotine (2 mg/kg s.c.) and black tea brewed (p.o.) each alone and in combination for 4 weeks. On the 28th day, myocardial damage was induced by isoproterenol (50 mg/kg i.p.), and blood samples were taken. On day 29, after hemodynamic parameters recording, hearts were removed for histopathological evaluation. Tea or nicotine consumption had no significant effects on hemodynamic indices of animals without heart damage. When the cardiac injury was induced, tea consumption maintained the maximum dp/dt, and nicotine significantly decreased the pressure-rate product. Moreover, severity of heart lesions was lower in the presence of nicotine or black tea. Concomitant use of these materials did not show extra effects on mentioned parameters more than the effect of each of them alone. The results suggest that subchronic administration of black tea or nicotine for a period of 4 weeks may have a mild cardioprotective effect, while concomitant use of these materials cannot intensify this beneficial effect.

Inhibition of endoplasm reticulum stress by anisodamine protects against myocardial injury after cardiac arrest and resuscitation in rats.

Anisodamine is a multi-functional bio-alkaloid with vascular activity. Our previous studies have revealed that anisodamine protects the heart from ischemia/reperfusion (I/R) injury induced by cardiac arrest (CA) and resuscitation. This study aimed to explore whether the protective effect of anisodamine is mediated by inhibition of the endoplasmic reticulum stress (ERS) response, which has been demonstrated to implicate in various I/R injuries. After 5 min of CA induced by electric stimulation, Wistar rats were randomly selected to receive cardiopulmonary resuscitation (CPR, including chest compression and epinephrine infusion) with or without anisodamine injection (n = 50/group). Hearts were harvested 24 h after the return of spontaneous circulation (ROSC). Sham-operated animals served as non-ischemic controls (n = 10). The survival rate, cardiomyocyte apoptosis, and the protein expression of ERS markers were detected. Thirty-three of the 50 rats in the Ani + CA/R group were successfully resuscitated, whereas only 18 of the 50 rats in the CA/R group gained ROSC. Survival to 24 h was significantly improved in the anisodamine treatment group (Ani + CA/R, n = 22/50) compared to the group with standard CPR (CA/R, n = 8/50). Anisodamine markedly decreased the number of apoptotic cardiomyocytes, the protein expression of GRP78, CHOP, and the active form of Caspase3 compared to the CA/R group. Our data suggest that anisodamine protects against cellular damage in rat hearts after CA and resuscitation, at least in part, by inhibiting myocardial ERS.

Management and clinical outcomes of acute cardiac tamponade complicating electrophysiologic procedures: a single-center case series.

BACKGROUND: Cardiac perforation with tamponade is an infrequent occurrence during an electrophysiologic procedure. The customary approach to management includes volume resuscitation followed by pericardiocentesis. Such a procedure, however, is not without its own risk, especially when performed emergently. We hypothesized that some patients experiencing this type of complication can be managed successfully in a conservative fashion, without the need for an additional invasive procedure. METHODS: We retrospectively analyzed the clinical outcomes and echocardiographic features of 33 consecutive patients who experienced this complication during cardiac electrophysiology (EP) procedures performed at our institution from 1988 to 2007. Nineteen patients (58%) were managed conservatively with intravenous fluids and vasopressors (Group A). Fourteen patients (42%) were managed invasively with pericardiocentesis (Group B). RESULTS: The mean systolic blood pressure at diagnosis did not differ between the two groups (64 vs 71 mmHg, P = 0.134). The mean lengths of hospitalization (4.7 vs 4.9 days, P = 0.75) and survival to hospital discharge (100% in both groups) were also similar. A large pericardial effusion (>or=2 cm) was seen predominantly among Group B patients. There was a statistically significant temporal trend toward managing this type of complication invasively (P = 0.038). CONCLUSION: Among patients who experience cardiac perforation as an acute complication of EP procedure, there appears to be a role for conservative management in a subset of patients who do not have echocardiographic evidence of a large effusion and who respond well to initial stabilizing measures consisting of fluids and vasopressors.

Protective effects of Salvia miltiorrhizae on the hearts of rats with severe acute pancreatits or obstructive jaundice.

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. METHODS: A total of 288 rats were used for SAP- (n=108) and OJ-associated (n=180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=15). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A2 (PLA2) in blood, and pathological changes of the hearts were investigated. RESULTS: The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P>0.05). The contents of endotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA2 (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P<0.01 and P<0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. CONCLUSION: In this study, we found that Salvia miltiorrhizae improved myocardial pathological changes, reduced the content of PLA2 in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats.

Modification of alterations in cardiac function and sarcoplasmic reticulum by astragaloside IV in myocardial injury in vivo.

Astragaloside IV, the primary pure saponin isolated from Astragalus membranaceus has been found to have potent cardioprotective effects. In this study, we aim to investigate if the beneficial effects of astragaloside IV on cardiac function are associated with improvement in sarcoplasmic reticulum Ca(2+)-pump function in myocardial injury in vivo. Myocardial injury in rats was induced by subcutaneous injection of a high dose of isoproterenol, and the therapeutic effect of astragaloside IV was observed. Isoproterenol-treated rats showed widespread subendocardial necrosis, a rise in serum lactate dehydrogenase and creatine kinase, formation of lipid oxide product malondialdehyde and inhibition of left ventricular diastolic and systolic function, which suggested severe myocardial injury and acute heart failure. Moreover, sarcoplasmic reticulum Ca(2+)-uptake ability and Ca(2+)-ATPase (SERCA2a) activity were significantly reduced. And the level of SERCA2a mRNA and protein expression was also markedly decreased, associated with a decrease in Ser(16)-phosphorylated phospholamban protein expression, while total phospholamban level was unchanged in the isoproterenol-treated group compared with controls. However, these biochemical and hemodynamic changes in the acute failing hearts were prevented by treatment of isoproterenol-induced rats with astragaloside IV. Likewise, the observed reductions in sarcoplasmic reticulum Ca(2+)-pump function as well as in SERCA2a mRNA and protein levels and the phosphorylation level of phospholamban in the injured hearts were attenuated by astragaloside IV treatment. These results suggest that the beneficial effect of astragaloside IV on isoproterenol-induced myocardial injury may be due to its ability to prevent changes of SERCA2a and Ser(16)-phosphorylated phospholamban protein expression and, thus, may prevent the depression in sarcoplasmic reticulum Ca(2+) transport and improve cardiac function.