Serum Creatine kinase-MB Research Articles

Apremilast reversed carfilzomib-induced cardiotoxicity through inhibition of oxidative stress, NF-κB and MAPK signaling in rats

Carfilzomib (CFZ), is a potent, selective second generation proteasome inhibitor, used for the treatment of multiple myeloma. The aim of the present study was to investigate the possible protective effect of apremilast (AP) on the CFZ -induced cardiotoxicity. Rats were randomly divided into four groups: Group 1, served as the control group, received normal saline. Group 2, served as the toxic group, received CFZ (4 mg/kg, intraperitoneally [i.p.]). Groups 3 and 4, served as treatment groups, and received CFZ with concomitant oral administration of AP in doses of 10 and 20 mg/kg/day, respectively. In the present study, administration of CFZ resulted in a significant increase in serum aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB), which were reversed by treatment with AP. CFZ resulted in a significant increase in heart malondialdehyde (MDA) contents and decrease in cardiac glutathione (GSH) level and catalase (CAT) enzyme activity which were significantly reversed by treatment with AP. Induction of cardiotoxicity by CFZ significantly increased caspase-3 enzyme activity which were reversed by treatment with AP. RT-PCR analysis revealed an increased mRNA expression of NF-κB, ERK and JNK which were reversed by treatment with AP in cardiac tissues. Western blot analysis revealed an increased expression of caspase-3 and NF-κB p65 and a decrease expression of inhibitory kappa B-alpha (Iκbα) with CFZ, which were reversed by treatment with AP. In conclusion, apremilast showed protective effect against CFZ-induced cardiotoxicity.

Effect of inhibition of GSK-3β activity on sevoflurane postconditioning-induced cardioprotection in diabetic rats

Objective To investigate the effect of inhibition of glycogen synthase kinase-3 beta(GSK-3β)activity on sevoflurane postconditioning-induced cardioprotection in diabetic rats. Methods Healthy adult male Sprague-Dawley rats, weighing 250-300 g, in which diabetes mellitus was induced by intraperitoneal 1% streptozotocin 60 mg/kg combined with high-fat and high-sucrose diet and confirmed by blood glucose level >16.7 mmol/L.Forty rats with diabetes mellitus were divided into 5 groups(n=8 each)using a random number table: sham operation group(S group), ischemia-reperfusion(I/R)group, sevoflurane postconditioning group(SP group), GSK-3β inhibitor SB216763 group(SB group), and sevoflurane postconditioning plus SB216763 group(SS group). Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.The rats inhaled sevoflurane with the end-tidal concentration of 2.5% for 5 min starting from 1 min before reperfusion in group SP.SB216763 0.2 mg/kg was injected via the caudal vein at 1 min before reperfusion in group SB.In group SS, the rats inhaled sevoflurane with the end-tidal concentration of 2.5% for 5 min starting from 1 min before reperfusion, and SB216763 0.2 mg/kg was injected via the caudal vein at 1 min before reperfusion.At 120 min of reperfusion, blood samples were collected from the carotid artery for determination of serum creatine kinase-MB(CK-MB)activity and cardiac troponin I(cTnI) concentrations.Myocardial specimens were collected at 120 min of reperfusion for microscopic examination of the pathological changes and for determination of myocardial infarct size(by 2, 3, 5-triphenyltetrazolium chloride staining)and phosphorylated GSK-3β(p-GSK-3β)expression(by Western blot). Results Compared with group S, the myocardial infarct size and serum CK-MB activity and cTnI concentration were significantly increased, and the expression of p-GSK-3β was significantly down-regulated in I/R, SP, SB and SS groups(P 0.05). Compared with group SB, the myocardial infarct size and serum CK-MB activity and cTnI concentration were significantly decreased, and the expression of p-GSK-3β was significantly up-regulated in group SS(P<0.05). The pathological changes of myocardium were significantly attenuated in SB and SS groups as compared with group I/R and group SP. Conclusion Inhibition of GSK-3β activity can improve sevoflurane postconditioning-induced cardioprotection in diabetic rats. Key words: Anesthetics, inhalation; Diabetes mellitus; Glycogen synthase kinase 3; Myocardial reperfusion injury

Impact of postconditioning with lactate-enriched blood on in-hospital outcomes of patients with ST-segment elevation myocardial infarction

BackgroundReperfusion injury offsets the beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI). In our previous reports, postconditioning with lactate-enriched blood (PCLeB) induced excellent microcirculation recovery and less inflammation in STEMI patients. This study aimed to determine the in-hospital outcomes of STEMI patients treated using PCLeB. MethodsFifty-five consecutive STEMI patients were treated using PCLeB (Age 66.6±13.8years, 76.4% men) within 12h of symptom onset. In our modified postconditioning protocol, the duration of each brief reperfusion was prolonged from 10s to 60s in a stepwise manner. Lactated Ringer's solution (20–30mL) was injected directly into the culprit coronary artery at the end of each brief reperfusion and the balloon was quickly inflated at the lesion site, whereby lactate could be trapped inside the ischemic myocardium. Each brief ischemic period lasted 60s. After 7cycles of balloon inflation and deflation, full reperfusion was performed. Thereafter, stenting was performed and percutaneous coronary intervention (PCI) was completed. ResultsThe mean corrected thrombolysis in myocardial infarction frame count was 20.1±10.1 after PCI completion. The mean peak serum creatine kinase and creatine kinase-MB levels were 2751±2227IU/L and 276±181IU/L respectively. None of the study patients died during their hospital stay or required continuation of oral diuretic or inotropic therapy for heart failure on discharge. ConclusionsPCLeB led to zero in-hospital mortality and no overt heart failure on discharge in 55 consecutive STEMI patients undergoing reperfusion therapy.

Protective Effects of Selenium, N-Acetylcysteine and Vitamin E Against Acute Ethanol Intoxication in Rats

The aim of this study was to determine possible protective influences of selenium (Se), N-acetylcysteine (NAC), and vitamin E (Vit E) against acute ethanol (EtOH) intoxication. Thirty-six rats were divided into six groups: I (control), II (EtOH), III (EtOH + Se), IV (EtOH + Vit E), V (EtOH + NAC), and VI (EtOH + mix). Except group I, EtOH was given the other pretreated (groups III, IV, V, and VI) and untreated groups (group II). Compared with the EtOH group, serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB levels were significantly decreased in all pretreated groups, whereas slightly diminished amylase and lipase were observed. Compared with the control group, a remarkably lower total antioxidant status (TAS), but higher total oxidant status (TOS), and oxidative stress index (OSI) were seen in brain, liver, and kidney tissues. The values of these parameters were less affected from EtOH-exposed brain tissue of EtOH + NAC and liver of EtOH + mix groups. Both significant decrease of catalase activity and marked increases of adenosine deaminase and myeloperoxidase were determined only in liver tissue of the EtOH group. Activities of these enzymes were restored in almost all pretreated groups. Moreover, an increase of xanthine oxidase activity was prevented in brain tissue of pretreated groups. In histopathological examination of the liver, hydropic degeneration, sinusoidal dilatation, mononuclear cell infiltration, and marked congestion, which were seen in the EtOH group, were prevented in all pretreated groups. Relative protection against acute EtOH toxicity, in both single and combined pretreatments of Se, NAC, and Vit E supplementation, was probably through antioxidant and free radical-neutralizing effects of foregoing materials.

Anti-myocardial ischemia effect of Syringa pinnatifolia Hemsl. by inhibiting expression of cyclooxygenase-1 and -2 in myocardial tissues of mice

Ethnopharmacological relevanceThe peeled stem of Syringa pinnatifolia Hemsl. (SP) is a traditional medicine in Inner Mongolia, China. The powder form of SP has been widely used for hundreds of years to relieve “He-Yi” related myocardial ischemia independently or in a traditional Chinese medicine preparation. Materials and methodsSP was extracted with 95% and 80% ethanol. Chemical profiling was performed using HPLC-DAD and IT-TOF-ESI-MS analyses. Myocardial ischemia was produced by ligation of the left anterior descending (LAD) coronary artery to evaluate the anti-myocardial ischemia effect of SP. Male C57BL/6 mice were randomly divided into six groups (n=10 per group): a sham group, a model group, groups pretreated with SP at three dosages (20mg/kg, 40mg/kg, and 80mg/kg, intragastrically), and a positive control group (acetylsalicylic acid, ASA, 53mg/kg, intragastrically). Echocardiography was performed to determine heart function by measuring ejection fraction and fractional shortening. The levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum, and 6-keto-PGF1α and TXB2 both in plasma and in protein homogenate of myocardial tissue were also measured. The levels of cyclooxygenase (COX)-1 and -2 in the heart tissue and their expressions in mouse myocardial tissue were determined using Western blot and an immunofluorescence assay, respectively. Inflammatory cell infiltration and collagen deposition changes in the myocardial ischemic tissue were observed by pathological examination. ResultsIntragastric pretreatment with SP produced a dose-dependent increase in cardiac function. SP at 80mg/kg significantly improved the EF (p<0.001) and FS (p<0.01) compared with the model group, as well as the levels of serum CK-MB and LDH decreased obviously (p<0.001), approaching those in the sham group. Besides, an obvious reduction in inflammatory cells infiltration and collagen deposition in the infarcted myocardial tissue was shown in each SP treatment group. In addition, SP increased 6-keto-PGF1α and decreased TXB2 levels in the plasma, whereas the opposite pattern was observed in the protein homogenate from the myocardial tissues at the infarction edge, but keeping balance the ratio of 6-keto-PGF1α and TXB2, which is better than ASA in plasma. The mechanisms is associated with the downregulated expressions of COX-1 (p<0.05) and COX-2 (p<0.001). ConclusionsEthanol extract of SP has a protective effect against myocardial ischemia via down regulation of COX-1 and COX-2 expression and by adjusting the ischemia-induced imbalance between 6-keto-PGF1α and TXB2. This study shows substantial evidence to support the clinical application of SP and indicates that such medicine has great potential for treating ischemia-induced heart disease.

Avaliação dos indicadores de lesão miocárdica em cães com leishmaniose visceral

O objetivo deste estudo foi avaliar os indicadores laboratoriais, eletrocardiográficos e histológicos de lesão cardíaca em diferentes grupos clínicos de cães com leishmaniose visceral. Foram analisados marcadores séricos, traçado eletrocardiográfico e fragmentos de tecido cardíaco de 41 cães naturalmente infectados, distribuídos em três grupos: assintomático, oligossintomático e sintomático. Todos os animais apresentaram aumento na atividade sérica da enzima creatina quinase fração MB. No traçado eletrocardiográfico, o complexo de baixa voltagem foi o distúrbio de condução mais frequente (8/10). Na análise histológica, 75,6% dos cães apresentaram reação inflamatória com predomínio de infiltrados linfo-histiocítico (13/31) de intensidade discreta a moderada e distribuição multifocal. As alterações microscópicas identificadas no miocárdio foram independentes dos achados laboratoriais, eletrocardiográficos e do quadro clínico apresentado pelos animais estudados. A ausência de associação entre alterações histopatológicas e os parâmetros investigados alerta para a dificuldade de identificação de cardiopatia em cães com leishmaniose visceral e ressalta a importância de incluir a leishmaniose visceral no diagnóstico de patologias cardíacas principalmente em regiões endêmicas para o agente.

Effect of sufentanil on autophagy during myocardial ischemia-reperfusion in rats

Objective To evaluate the effect of sufentanil on autophagy during myocardial ischemia-reperfusion(I/R)in rats. Methods Eighteen adult male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into 3 groups(n=6 each)using a random number table: sham operation group(group SH), I/R group, and sufentanil group(group S). Myocardial I/R injury was produced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion in the rats anesthetized with chloral hydrate in I/R and S groups.Sufentanil 3 μg/kg was injected via the caudal vein at 30 min prior to ischemia in group S. The equal volume of normal saline was given in SH and I/R groups.At 120 min of reperfusion, arterial blood samples were collected for determination of serum creatine kinase-MB(CK-MB)and lactic dehydrogenase(LDH)concentrations, and myocardial specimens were obtained for examination of the ultrastructure of myocardial cells(using transmission electron microscopy)and for determination of autophagy-related proteins microtubule-associated protein 1 light chain 3 Ⅱ(LC3Ⅱ), Beclin-1 and Bcl-2 expression(by Western blot). Results Compared with group SH, the serum CK-MB and LDH concentrations were significantly increased, the expression of LC3Ⅱ and Beclin-1 was significantly up-regulated, and Bcl-2 expression was significantly down-regulated in group I/R, and the serum CK-MB concentration was significantly increased, the expression of Beclin-1 and Bcl-2 was significantly down-regulated in group S(P 0.05), and the pathological changes were reduced in group S. Conclusion The mechanism by which sufentanil reduces myocardial I/R injury may be related to decreased autophagy in rats. Key words: Sufentanil; Myocardial reperfusion injury; Autophagy

Effect of aliskiren and carvedilol on expression of Ca2+/calmodulin-dependent protein kinase II δ-subunit isoforms in cardiac hypertrophy rat model

Context: The critical role of CaMKIIδ isoforms in cardiac hypertrophy is well documented.Objective: This study was aimed to investigate the possible inhibitory effects of aliskiren (ALS) and/or carvedilol (CAV) on CaMKIIδ isoforms expression in experimental cardiac hypertrophy.Materials and methods: Male Wistar albino rats were subcutaneously injected with isoproterenol (ISO) (5 mg/kg/day) for 4 weeks to induce cardiac hypertrophy. Hypertrophied rats were daily treated with either ALS (10 mg/kg) and/or CAV (10 mg/kg). At the end of the treatment, rats were killed; blood and hearts were collected for assessing different biochemical parameters.Results: ISO treatment significantly increased heart weight to body weight (HW/BW) ratio, serum creatine kinase MB (CK-MB) and troponin T (Tn-T) levels, and plasma renin activity (PRA) as compared to control rats. Additionally, ISO treatment produced a significant increase in the expression of myocardial CaMKIIδ2 and CaMKIIδ3 that were associated with significant elevation in myocardial caspase-3 protein expression. Histopathological examination of rats exposed to ISO treatment showed severe myocardial cell degeneration. ALS and/or CAV treatment significantly reduced the altered HW/BW ratio, serum CK-MB and Tn-T levels, PRA, and caspase-3 protein expression in hypertrophied rats, with maximal improvement in the combination group. These biochemical findings were supported by the histopathological examination of the heart tissue. Additionally, treatment with ALS and CAV significantly inhibited ISO-induced increase in CaMKIIδ2 and CaMKIIδ3 expression levels.Discussion and conclusion: The present study indicated that ALS and CAV treatment ameliorated ISO-induced hypertrophy via inhibiting the expression and the activity of CaMKIIδ isoforms and the associated myocardial apoptosis.

The relevance of the serum levels of C-reactive protein and creatine kinase-MB to the severity of hand-foot-and-mouth disease patients in China: A meta-analysis

Abstract Objective The goal of this meta-analysis was to determine whether the serum levels of C-reactive protein (CRP) and creatine kinase-MB (CK-MB) are correlated with the severity of hand-foot-and-mouth disease (HFMD). Methods We conducted a systematic search and meta-analysis of the MEDLINE, PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, VIP information, and Wanfang Chinese Periodical databases. The analysis included all published case–control, cohort, and cross-sectional studies of serum CRP and/or CK-MB levels in children with HFMD up to December 4, 2014. Pooled estimates were calculated using a random-effects model or a fixed-effects model. Results Thirty-eight articles are included in this meta-analysis. The summary estimates revealed that the average serum CRP levels, prevalence of high CRP, average serum CK-MB levels, and prevalence of high CK-MB increased with the severity of HFMD. There were no significant differences in the average levels of serum CK-MB (pooled MD = 22.29 U/L; 95% CI: −0.82–45.39 U/L, P = 0.06) between patients who were critically ill and those with severe HFMD. Therefore, we compared the average levels of serum CRP (pooled MD = 1.17 mg/L; 95% CI: −0.88–3.21 mg/L, P = 0.26) between patients infected with enterovirus 71 and those infected with coxsackievirus A16. Conclusions The result of these analyses indicated that the CRP and CK-MB levels are correlated with HFMD severity. Thus, these frequently used and accessible measures may aid clinicians in effectively diagnosing, treating, and predicting the prognosis of children with HFMD.

Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice.

Doxorubicin is a widely used anthracycline derivative anticancer drug. Unfortunately, the clinical use of doxorubicin has the serious drawback of cardiotoxicity. In this study, we investigated whether baicalein, a bioflavonoid, can prevent doxorubicin-induced cardiotoxicity in vivo and we delineated the possible underlying mechanisms. Male BALB/c mice were treated with either intraperitoneal doxorubicin (15 mg/kg divided into three equal doses for 15 days) and/or oral baicalein (25 and 50 mg/kg for 15 days). Serum markers of cardiac injury, histology of heart, parameters related to myocardial oxidative stress, apoptosis and inflammation were investigated. Treatment with baicalein reduced doxorubicin-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and ameliorated the histopathological damage. Baicalein restored the doxorubicin-induced decrease in both enzymatic and non-enzymatic myocardial antioxidants and increased the myocardial expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Further studies showed that baicalein could inverse the Bax/Bcl-2 ratio, suppress doxorubicin-induced p53, cleaved caspase-3 and PARP expression and prevented doxorubicin-induced DNA damage. Baicalein treatment also interferes with doxorubicin-induced myocardial NF-κB signaling through inhibition of IκBα phosphorylation and nuclear translocation of p65 subunit. Doxorubicin elevated iNOS and nitrites levels were also significantly decreased in baicalein treated mice. However, we did not find any significant change (p>0.05) in the myocardial TNF-α and IL-6 levels in control and treated animals. Our finding suggests that baicalein might be a promising molecule for the prevention of doxorubicin-induced cardiotoxicity.

Effects of pretreatment with recombinant human B-type natriuretic peptide on infarct size in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

To investigate whether the administration of recombinant human B-type natriuretic peptide (rhBNP) before primary percutaneous coronary intervention (PCI) could further limit the infract size, improve left ventricular function, and alleviate cardiac dilation in patients with acute ST-segment elevation myocardial infarction(STEMI). A total of 93 consecutive patients presenting chest pain within 12 hours from the onset, suspicious of first STEMI located at anterior wall undergoing primary PCI, were eligible for enrollment and randomly assigned to either rhBNP group (rhBNP administration starting at 5 min before PCI, 1.5 µg/kg bolus intravenous injection followed by 0.007 5-0.03 µg·kg(-1)·min(-1) for up to 120 hours, n=48) or nitroglycerin (NIT) group (NIT treatment starting at 5 min before PCI, 10-100 µg/min intravenous infusion for 120 hours, n=45). Primary PCI was performed in both groups using post-conditioning (PC) technique. TIMI flow grade, corrected TIMI frame count, and TIMI myocardial perfusion grade were compared between the two groups at the time of infarct related artery (IRA) re-patency. The levels of serum creatine kinase MB isoenzyme (CK-MB) and troponin I (TnI) were measured. Echocardiography was performed at baseline 7 days and 6 months later. Baseline characteristics were similar between the two groups. The percentage of TIMI grade 3 and TIMI myocardial perfusion grade 3 after PCI both tended to be higher in rhBNP group than those in NIT group (95.8%(46/48) vs. 86.7%(39/45), P=0.162) and (72.9%(35/48) vs. 62.2%(28/45), P=0.500). The corrected TIMI frame count was significantly decreased in rhBNP group (21.0±8.7 vs. 28.2±14.8, P=0.005). The myocardial infarct size expressed as the AUC of CK-MB ((3 249±1 101) U/L vs. (4 474±1 661)U/L, P=0.010) or AUC of TnI ((3 670±942) µg/L vs. (4 541±1 098) µg/L, P=0.021) was significantly decreased in rhBNP group compared with those in NIT group. At 7 days after primary PCI, the left ventricular ejection fraction (LVEF) tended to be higher (P>0.05), while the E/e' index and wall motion score index (WMSI) ((11.95±3.31 vs. 14.60±4.09, P=0.030) and (1.74±0.17 vs. 2.40±0.55, P<0.001)) were significantly improved in rhBNP group compared with those in NIT group. BNP level was also significantly lower in rhBNP group compared that in NIT group ((68.3±37.8) ng/L vs. (129.4±64.4) ng/L, P<0.001). During 6-month follow-up, LVEF and WMSI were significantly improved in rhBNP group compared those in NIT group(51.7%±12.7% vs. 46.9%±9.6%, P=0.024 and 1.69±0.35 vs. 1.92±0.47, P=0.020). Administration of rhBNP before PCI with post-conditioning procedure can further improve myocardial perfusion, limit myocardial infarct size, ameliorate cardiac dysfunction and postpone left ventricular early-stage and long-term remodeling in STEMI patients undergoing primary PCI.

Puerarin attenuates severe burn-induced acute myocardial injury in rats

BackgroundPuerarin, the main isoflavone glycoside extracted from the root of Pueraria lobata, is widely prescribed for patients with cardiovascular disorders in China. This study investigates the effect of puerarin on severe burn-induced acute myocardial injury in rats and its underlying mechanisms. Materials and methodsHealthy adult Wistar rats were divided into three groups: (1) sham group, sham burn treatment; (2) burn group, third-degree burns over 30% of the total body surface area (TBSA) with lactated Ringer's solution for resuscitation; and (3) burn plus puerarin group, third-degree burns over 30% of TBSA with lactated Ringer's solution containing puerarin for resuscitation. The burned animals were sacrificed at 1, 3, 6, 12, and 24h after burn injury. Myocardial injury was evaluated by analyzing serum creatine kinase MB fraction (CK-MB) activity and cardiac troponin T (cTNT) level. Changes in cardiomyocyte ultrastructure were also determined using a transmission electron microscope. Tumor necrosis factor (TNF)-α concentration in serum was measured by radioimmunoassay. Cardiac myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to determine neutrophil infiltration and oxidative stress in the heart, respectively. The expression of p38 mitogen-activated protein (MAP) kinase in the heart was determined by Western blot analysis. ResultsAfter the 30% TBSA full-thickness burn injury, serum CK-MB activities and cTnT levels increased markedly, both of which were significantly decreased by the puerarin treatment. The level of serum TNF-α concentration in burn group at each time-point was obviously higher than those in sham group (1.09±0.09ng/ml), and it reached the peak value at 12h post burn. Burn trauma also resulted in worsen ultrastructural condition, elevated MPO activity and MDA content in heart tissue, and a significant activation of cardiac p38 MAP kinase. Administration of puerarin improved the ultrastructural changes in cardiomyocytes, decreased TNF-α concentration in serum as well as suppressed cardiac MPO activity and reduced MDA content, and abolished the activation of p38 MAP kinase in heart tissue after severe burn. ConclusionsThese results suggest that puerarin attenuates inflammatory responses, reduces neutrophil infiltration and oxidative stress in the heart, and protects against acute myocardial injury induced by severe burn.

SIRT1 protects against myocardial ischemia-reperfusion injury via activating eNOS in diabetic rats.

BackgroundDiabetic patients are more sensitive to myocardial ischemic injury than non-diabetic patients. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent histone deacetylase making the heart more resistant to ischemic injury. As SIRT1 expression is considered to be reduced in diabetic heart, we therefore hypothesized that up-regulation of SIRT1 in the diabetic heart may overcome its increased susceptibility to ischemic injury.MethodsMale Sprague–Dawley rats were fed with high-fat diet and injected with streptozotocin once to induce diabetes. Diabetic rats received injections of adenoviral vectors encoding SIRT1 (Ad-SIRT1) at five myocardial sites. Four days after adenoviral injection, the rats were subjected to myocardial ischemia and reperfusion (MI/R). Outcome measures included left ventricular function, infarct size, cellular death and oxidative stress.ResultsDelivery of Ad-SIRT1 into the hearts of diabetic rats markedly increased SIRT1 expression. Up-regulation of SIRT1 in diabetic hearts improved cardiac function and reduced infarct size to the extent as in non-diabetic animals following MI/R, which was associated with reduced serum creatine kinase-MB, lactate dehydrogenase activities and cardiomyocyte apoptosis. Moreover, Ad-SIRT1 reduced the increase in the superoxide generation and malonaldialdehyde content and simultaneously increased the antioxidant capability. Furthermore, Ad-SIRT1 increased eNOS phosphorylation and reduced eNOS acetylation in diabetic hearts. NOS inhibitor L-NAME inhibited SIRT1-enhanced eNOS phosphorylation, and blunted SIRT1-mediated anti-apoptotic and anti-oxidative effects and cardioprotection.ConclusionsOverexpression of SIRT1 reduces diabetes-exacerbated MI/R injury and oxidative stress via activating eNOS in diabetic rats. The findings suggest SIRT1 may be a promising novel therapeutic target for diabetic cardiac complications.

Protective effect of Suxiao jiuxin pill, a traditional Chinese medicine, against acute myocardial ischemia in dogs.

BackgroundThe purpose of this study was to investigate the effect of Suxiao Jiuxin Pill (SX), a traditional Chinese medicine, on acute myocardial ischemia induced by coronary occlusion in anesthetized dogs.MethodsAcute myocardial ischemia model was established by ligating the left anterior descending artery to reduce flow by 90 %. Adult mongrel dogs were randomly divided into six groups: model, SX high dose, SX middle dose, SX low dose, Isosorbide dinitrate (ISD) and Sham groups. Adult mongrel dogs were anesthetized and instrumented for measurements of heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular dP/dt, coronary blood flow (CBF), myocardial blood flow (MBF), coronary vascular resistance (CVR), and epicardial electrocardiogram (EECG). After administration with SX, changes in hemodynamics were recorded. Serum enzymes and blood gas analysis were also detected.ResultsSX has a dose-dependent effect on the reduction of infarct size. Besides, SX exerted a notable inhibition on the elevation of serum creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA), and elevation in the superoxide dismutase (SOD) activity. SX also showed a capacity to recover myocardial function by significantly reducing MAP, CVR, LVSP, left ventricular systolic pressure (LVEDP), systolic blood pressure (SBP), diastolic blood pressure (SDP), and increasing CBF and myocardial blood flow (MBF). In addition, SX high dose group markedly reduced total mV of ST segment elevation (Σ-ST), total number of sites with this degree of ST segment elevation (N-ST) and oxygen extraction ratio (O2 Extr).ConclusionSX can improve hemodynamic and myocardial oxygen metabolism, reduce the degree and scope of myocardial ischemia, and hence exert notable anti-anginal ischaemic effect.

Protective Effects of 7-Hydroxycoumarin on Dyslipidemia and Cardiac Hypertrophy in Isoproterenol-Induced Myocardial Infarction in Rats.

This study evaluates the protective effects of 7-hydroxycoumarin (7-HC) on dyslipidemia and cardiac hypertrophy in isoproterenol (ISO) induced myocardial infarction (MI) in rats. Rats were pre- and co treated with 7-HC (16 mg/kg) daily for 8 days. ISO (100 mg/kg) was subcutaneously injected into rats on seventh and eighth days to induce MI. Increased activity/levels of serum creatine kinase-MB (CK-MB), troponin-T, plasma lipid peroxidation products, and altered levels of lipids in the serum and heart and serum lipoproteins were noted in ISO-induced rats. ISO-induced myocardial infarcted rats revealed increased hypertrophy (cardiac and left ventricular) and hepatic 3-hydroxyl 3-methylglutaryl-coenzyme-A reductase (HMG-CoA reductase) activity. Pre and cotreatment with 7-HC revealed significant protective effects on all the biochemical parameters evaluated. The in vitro study demonstrated its free radical scavenging property. Thus, 7-HC protects ISO-induced MI in rats by its free radical scavenging and antihyperlipidaemic and antihypertrophic properties.

BET protein inhibition mitigates acute myocardial infarction damage in rats via the TLR4/TRAF6/NF-κB pathway.

Acute myocardial infarction (AMI) is among the most serious cardiovascular diseases and is a leading cause of mortality in developed countries. Previous studies have indicated the central role played by the bromodomain (BRD) proteins, which belong to the BRD and extra-terminal (BET) family, in gene control during heart failure pathogenesis. In addition, BET inhibition has been shown to suppress cardiomyocyte hypertrophy. However, the role of BET proteins in myocardial infarction remains unclear. The present study aimed to investigate whether BETs inhibition mitigates AMI, and explore the molecular mechanism underlying this effect. A rat model of acute myocardial infarction was established, and rats were divided into the sham, AMI and AMI + JQ1 groups. JQ1, a well-known selective BRD inhibitor, was used to suppress BET domain family activity. The mRNA and protein expression levels of BRD2, BRD3 and BRD4 were evaluated using quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the expression levels of markers of cardiac damage were determined using commercial kits. The results indicated that BRD2 and BRD4 mRNA and protein expression levels were significantly increased in the AMI group compared with those in the sham group. In addition, BET inhibition decreased AMI damage in vivo by reversing cardiac function injury, decreasing serum lactate dehydrogenase and creatine kinase-MB isozyme activity, in addition to decreasing the expression levels of high-sensitivity C-reactive protein and interleukin-6. Furthermore, the results suggested that Toll-like receptor 4 (TLR4) signaling was activated by the increased expression of TLR4, TNF receptor-associated factor 6 (TRAF6) and nuclear factor (NF)-κB during AMI. However, JQ1 treatment suppressed TLR4 signaling activation. In conclusion, the present results demonstrated that the inhibition of BET family proteins suppresses AMI, and that this effect was partially mediated by the inhibition of TLR4/TRAF6/NF-κB signaling.

The Possible Cardio-Reno- Protective Effects of Vanillin on Isopretrenol- Induced Myocardial Infarction in Rats

Myocardial infarction (MI) continues to be a major public health problem in the world. Vanillin is a natural phenolic compound that possesses significant anti-oxidant and anti-inflammatory activities. The present study aimed to investigate the effects of pretreatment with vanillin (150 mg/kg, p.o.) and vanillin (300 mg/kg, p.o.) on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), in addition to serum level of cardiac troponin-I (cTn-I), as well as antioxidant activity of cardiac catalase (CAT) as well as cardiac contents of RGH, lipid peroxides, and nitrite. Furthermore Electrocardiograph (ECG) monitoring and histological examinations of cardiac tissues were done. In addition markers chosen to assess renal impairment included serum and urine levels of creatinin, blood urea nitrogen (BUN), also creatinine clearance (Ccr), urea clearance (Ucr) and glomerular filteration rate (GFR) were assessed. In addition, antioxidant activity of renal CAT and renal contents of RGH, lipid peroxides, and nitrite. Furthermore, histological examinations of renal tissues were done. Isoprenaline increased serum CK-MB and LDH activity and cTn-I level, cardiac and renal oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart and renal tissues. Pretreatment with vanillin in previous doses significantly suppressed isoprenaline-induced pathological changes, as the elevated levels of cTn-I, LDH and CK-MB in serum coupled with reduction in cardiac and renal oxidative stress markers. Moreover marked improvement in ECG and histopathologic alterations in both cardiac and renal tissues were produced. In conclusion, vanillin can be regarded as a promising cardio- and reno- protective natural agent in MI.

Dexmedetomidine Attenuates Myocardial Injury in Off-Pump Coronary Artery Bypass Graft Surgery.

To investigate the cardioprotective effect of the continuous administration of dexmedetomidine using serum cardiac troponin I (cTnI) and creatine kinase MB (CK-MB) concentrations as biomarkers during off-pump coronary artery bypass grafting (OPCAB) surgery. A prospective, randomized, parallel-group controlled study. A university hospital. One hundred sixteen patients undergoing OPCAB surgery. Patients were divided randomly into 3 experimental groups that were separated by the dexmedetomidine administration protocol: a high-dose group (loading dose, 1 μg/kg; maintenance dose, 0.6 μg/kg/h); low-dose group (loading dose, 0.6 μg/kg; maintenance dose, 0.3 μg/kg/h); and control group (the same amount of 0.9% saline as placebo). Serum cTnI and CK-MB levels were measured before surgery and 24 hours and 48 hours after surgery. Serum cTnI and CK-MB levels in patients of the high-dose group were less than those of the other 2 groups 48 hours after surgery. The administration of dexmedetomidine significantly decreased the heart rate. Compared with the control group, there was a significantly reduced requirement of sevoflurane in the other 2 groups (p<0.05). The intraoperative and postoperative cumulative volumes of urine output in the high-dose group were greater than those of the other 2 groups (p<0.05). The authors also found that the extubation time and length of stay in the intensive care unit were prolonged in the high-dose group. Myocardial damage was reduced by the administration of a 1 μg/kg loading dose and a 0.6 μg/kg/h infusion dose of dexmedetomidine. However, further studies are needed to understand the underlying mechanism and to confirm that high doses of dexmedetomidine could be administered safely in patients undergoing OPCAB surgery.

A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats

Acute kidney injury (AKI) is associated with high mortality resulting from extra-renal organ damage, particularly the heart. The present study aimed to investigate the protective effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, against renal and remote cardiac damage induced by ischemia/reperfusion (IR), a leading cause of AKI. In this attempt, we compared the effects of sitagliptin to furosemide, a loop diuretic. Furosemide is commonly used clinically in AKI however, there is a lack of evidence regarding its beneficial effects in AKI. In addition, the combined administration of both drugs was also investigated. Ischemia was induced in anesthetized male Wistar rats by occluding both renal pedicles for 30min followed by reperfusion for 24h. Sitagliptin (5mgkg−1), furosemide (245mgkg−1) or their combination were administered orally at 5h post-IR and 2h before euthanasia. Administration of sitagliptin or furosemide ameliorated renal and cardiac deterioration induced by renal IR. This was manifested as significant reduction of serum creatinine, urea, cystatin c, creatine kinase-MB, cardiac troponin-I and lactate dehydrogenase (P<0.05). Drug treatment significantly inhibited IR-induced elevation of TNF-α, NF-κB and caspase-3 (P<0.05) in kidney and heart tissue. In addition, they significantly suppressed malondialdehyde, NO and iNOS content, whereas they increased glutathione and antioxidative enzymes activity (P<0.05) in both tissues. Interestingly, a superior protection was observed with the combination compared to the individual drugs. We assume that this combination represents a promising regimen for managing AKI, particularly with the poor clinical outcome obtained with furosemide alone.

Circulating miR-499 are novel and sensitive biomarker of acute myocardial infarction.

miRNAs are known to play a crucial role in cardiac development, and the expression of miRNA is altered in the diseased heart. The aim of this study was to investigate the value of plasma microRNA-499 (miR-499) as a novel biomarker for early diagnosis of acute myocardial infarction (AMI). Enrolled in this study were 227 patients with chest pain on presentation to the departments of emergency and cardiology of Wuxi Second People's Hospital between October 2011 and May 2014. Additional 100 healthy individuals who received physical examination in the same hospital during the same period were used as control. Plasma was collected at admission, and the abundance of miR-499 was measured using reverse transcriptase-polymerase chain reaction (RT-PCR). MiR-499 was significantly elevated in 142 patients diagnosed with AMI as compared with 85 patients in non-AMI group and 100 subjects in healthy control group. Plasma miR-499 were already detectable in the plasma as early as 1 h after onset of chest pain in AMI patients, and continued to increase gradually without any sign of decreasing tendency within 9 h in AMI patients. miR-499 was highly positively correlated with the serum creatine kinase-MB (CK-MB) and cTnI. The area under the curve (AUC) of miR-499 for the diagnosis of AMI was 0.86, with an optimal cut-off value of 4.79, sensitivity of 80%, and specificity of 80.28%. miR-499 was shown to substantially increase the diagnostic accuracy of CK-MB and cTnI in the diagnosis of AMI, and therefore it may prove to be a useful marker for early diagnosis of AMI.