Kinase Isoenzyme MB Research Articles

Carperitide and Atrial Fibrillation After Coronary Bypass Grafting

Background— Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. Methods and Results— A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group ( P <0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid–binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of β-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. Conclusions — Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing postoperative atrial fibrillation. Clinical Trial Registration — URL: http://www.umin.ac.jp . Unique Identifier: UMIN000003958.

Protective effects of the standardized extract of Zingiber officinale on myocardium against isoproterenol-induced biochemical and histopathological alterations in rats

Context: Ginger [Zingiber officinale Roscoe. (Zingiberaceae)] has been universally used as a spice as well as for its health benefits.Objective: The present study evaluates the protective effect of the standardized extract of ginger against isoproterenol (ISO)-induced myocardial infarction (MI) in rats.Materials and methods: Wistar rats were pretreated orally with three doses of standardized ginger extract (100, 200, and 400 mg/kg of body weight) or propranolol (5 mg/mL) for 28 d prior to ISO (85 mg/kg) induced MI in two doses on days 29 and 30. The rats were sacrificed 48 h after the first induction; serum and hearts were collected for biochemical and histopathological analysis.Results: Gingerols and shogaols were identified and quantitatively analyzed in the extracts using validated reversed phase HPLC methods. Pretreatment with ginger extract at 400 mg/kg showed a significant decrease (p < 0.05) in all the cardiac enzyme activities, i.e., cardiac troponin I (cTnI) (0.57 ng/mL), creatine kinase MB isoenzyme (CK-MB) (10.34 pg/mL), lactate dehydrogenase (LDH) (115.22 U/L), alanine transaminase (ALT) (15.79 U/L), and aspartate transaminase (AST) (46.72 U/L) when compared with ISO-control rats. There were significant rises (p < 0.05) in the activity of glutathione peroxide (GPx) (53.16 U/L), catalase (CAT) (210.41 U/L), and superoxide dismutase (SOD) (280.89 U/mL) of the pretreated rats when compared with the ISO-control. Histopathological examination showed an improvement in membrane cell integrity in pretreated rats compared with untreated rats.Conclusion: The ethanol extract of ginger exhibited cardioprotective potential in treating myocardial injury following ISO administration.

Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery

ObjectivesIdentification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought...

Boswellic acids synergize antitumor activity and protect against the cardiotoxicity of doxorubicin in mice bearing Ehrlich's carcinoma.

This study aimed to test whether boswellic acids add to the antitumor effects of doxorubicin against solid tumors of Ehrlich's ascites carcinoma (EAC) grown in mice, and to investigate the protective effects of boswellic acids against doxorubicin-induced cardiotoxicity. Sixty-four female Swiss albino mice bearing EAC solid tumors were distributed among 8 groups as follows: group 1, EAC control group; group 2, doxorubicin treatment group [mice were injected with doxorubicin (6 mg·(kg body mass)(-1)·week(-1)) for 3 weeks]; groups 3-5, these mice were treated with boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively; groups 6-8, these mice were treated with a combination of doxorubicin and boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively, for 3 weeks. The results indicated that boswellic acids synergized the antitumor activity of doxorubicin. Doxorubicin-treated mice showed elevated serum activities of lactate dehydrogenase and creatine kinase isoenzyme MB as well as cardiac malondialdehyde. Further, decreases in cardiac levels of reduced glutathione, superoxide dismutase, and catalase activities were observed. These effects were accompanied by an increase in cardiac expression of caspase 3. Thus, treatment with boswellic acids attenuated doxorubicin-evoked disturbances in the above-mentioned parameters, highlighting antioxidant and antiapoptotic activities. Therefore, boswellic acids could be potential candidates for ameliorating the cardiotoxicity of doxorubicin.

Protective effects of Labisia pumila var. alata on biochemical and histopathological alterations of cardiac muscle cells in isoproterenol-induced myocardial infarction rats.

The study was designed to evaluate the cardioprotective effects of the standardized aqueous and 80% ethanol extracts of Labisia pumila var. alata (LPva) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. The extracts were administered to Wistar rats orally for 28 days with three doses (100, 200 and 400 mg/kg of body weight) prior to ISO (85 mg/kg)-induced MI in two doses on day 29 and 30. The sera and hearts were collected for biochemical and histopathological analysis after the rats were sacrificed 48 h after the first induction. The main components of the extracts, gallic acid, alkylresorcinols and flavonoids were identified and quantitatively analyzed in the extracts by using a validated reversed phase HPLC method. The extracts showed significant protective effects as pretreated rats showed a significant dose-dependent decrease (p < 0.05) in cardiac enzyme activities, i.e., cardiac troponin I (cTnI), creatine kinase MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST), when compared with ISO-control rats. There were significant rises (p < 0.05) in the activity of oxidase enzymes, i.e., glutathione peroxide (GPx), catalase (CAT) and superoxide dismutase (SOD) of the pretreated rats, when compared with ISO-control group. Histopathological examination showed an improvement in membrane cell integrity in pre-treated rats compared to untreated rats. The major components of LPva extracts can be used as their biomarkers and contributed to the cardioprotective effects against ISO-induced MI rats.

Efeito da suplementação com vitamina E sobre os metabolismos oxidativo e cardíaco em equinos submetidos a exercício de alta intensidade

A suplementação antioxidante visa prevenir os danos oxidativos induzidos pelo exercício físico em diversos tecidos, como o miocárdio. Nesse contexto, este estudo objetivou avaliar os marcadores cardíacos e a lipoperoxidação em equinos no teste de exercício de rápida aceleração e curta duração (TRA), em esteira de alta velocidade, antes e após a suplementação com vitamina E. Para tanto, foram utilizados 10 equinos sem treinamento, que realizaram o primeiro TRA (TRA1) com carga de trabalho fundamentada no consumo máximo de oxigênio individual (VO2max) e que induziu a concentração de lactato maior que 4mmol/L, sendo considerado predominantemente anaeróbico. Em seguida, os equinos receberam vitamina E (dl-alfa-tocoferol) na dose de 1.000UI/dia, por via oral, durante 52 dias, e, posteriormente, realizaram um segundo TRA (TRA2) com o mesmo protocolo de TRA1. As amostras de sangue foram colhidas nos momentos antes do exercício, imediatamente após o término do teste e em 1h, 3h, 6h, 12h e 24h subsequentes. Determinou-se o malondialdeído (MDA) plasmático como índice de lipoperoxidação, e as concentrações séricas de troponina I cardíaca (cTnI), isoenzima MB da creatinoquinase (CK-MB) e mioglobina, como marcadores cardíacos. Como efeito do exercício, observou-se aumento discreto de MDA, de cTnI e de CK-MB, sendo significativo apenas para CK-MB. A suplementação foi capaz de amenizar a produção das espécies reativas de oxigênio, evidenciada pela menor concentração de MDA em TRA2, em 24h, além de causar um efeito protetor no miocárdio, devido ao menor valor de cTnI em 6h no TRA2 em relação ao TRA1. Não houve grandes alterações na concentração de mioglobina. Concluiu-se que o exercício de alta intensidade promoveu estresse no miocárdio nos equinos avaliados, bem como houve efeito benéfico da vitamina E na proteção miocárdica e sobre a lipoperoxidação.

Protective effect against myocardial ischemia reperfusion injuries induced by hyperoside preconditioning and its relationship with PI3K/Akt signaling pathway in rats

To investigate the protective effect of preconditioning with hyperoside ( Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats. Male SD rats were randomly divided into five groups: sham group,model group (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and maximal rate of increase and decrease of left ventricular pressure (± dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function, reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI, such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors, for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2 protein and down-regulating the expression of Bax protein.

A novel Alu-based real-time PCR method for the quantitative detection of plasma circulating cell-free DNA: sensitivity and specificity for the diagnosis of myocardial infarction.

In the present study, we aimed to develop and validate a rapid and sensitive, Alu-based real-time PCR method for the detection of circulating cell-free DNA (cfDNA). This method targeted repetitive elements of the Alu reduplicative elements in the human genome, followed by signal amplification using fluorescence quantification. Standard Alu-puc57 vectors were constructed and 5 pairs of specific primers were designed. Valuation was conducted concerning linearity, variation and recovery. We found 5 linear responses (R1–5=0.998–0.999). The average intra- and inter-assay coefficients of variance were 12.98 and 10.75%, respectively. The recovery was 82.33–114.01%, with a mean recovery index of 101.26%. This Alu-based assay was reliable, accurate and sensitive for the quantitative detection of cfDNA. Plasma from normal controls and patients with myocardial infarction (MI) were analyzed, and the baseline levels of cfDNA were higher in the MI group. The area under the receiver operating characteristic (ROC) curve for Alu1, Alu2, Alu3, Alu4, Alu5 and Alu (Alu1 + Alu2 + Alu3 + Alu4 + Alu5) was 0.887, 0.758, 0.857, 0.940, 0.968 and 0.933, respectively. The optimal cut-off value for Alu1, Alu2, Alu3, Alu4, Alu5 and Alu to predict MI was 3.71, 1.93, 0.22, 3.73, 6.13 and 6.40 log copies/ml. We demonstrate that this new method is a reliable, accurate and sensitive method for the quantitative detection of cfDNA and that it is useful for studying the regulation of cfDNA in certain pathological conditions. Alu4, Alu5 and Alu showed better sensitivity and specificity for the diagnosis of MI compared with cardiac troponin I (cTnI), creatine kinase MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH). Alu5 had the best prognostic ability.

Safety of single-dose histidine-tryptophan-ketoglutarate cardioplegia during minimally invasive mitral valve surgery.

Minimally invasive mitral valve surgery may require a prolonged period of myocardial ischemia. Cardioplegic solutions that necessitate a single dose for adequate myocardial protection are evoked to simplify surgery and result to be appealing in this setting. The aim of this study was to assess early outcomes after minimally invasive mitral valve surgery using one single dose of histidine-tryptophan-ketoglutarate solution (HTK; Custodiol) for myocardial protection. Between February 2003 and October 2012, a total of 49 consecutive patients underwent minimally invasive mitral valve surgery using a single dose of HTK solution for myocardial protection. The patients' mean (SD) age was 57 (14) years; the preoperative ejection fraction was normal in all cases. The mean (SD) CPB time and aortic cross-clamp time were 148 (45) minutes and 97 (45) minutes, respectively. The heart spontaneously restarted after cross-clamp removal in 37 patients (75.5%). Five patients (10.2%) required prolonged inotropic drug support. Postoperatively, no significant increase in myocardial cytonecrosis enzymes was found [mean (SD) creatine kinase isoenzyme MB, 77.14 (53.67) μg/L at 3 hours, 71.2 (55.67) μg/L at 12 hours, and 42.53 (38.38) μg/L at 24 hours)], and no ischemic electrocardiogram modifications were observed before discharge. During minimally invasive mitral valve surgery, HTK solution provided excellent myocardial protection even after prolonged periods of cardioplegic arrest. The avoidance of repetitive infusions may reduce the risk for coronary malperfusion due to dislodgement of the endoaortic clamp (if used) and increase the surgeon's comfort during the procedure.

Parenteral clinical manifestations of 68 cases caused by rotaviral enteritis

Objective To analyze rotaviral enteritis outbreak situation parenteral clinical manifestations and understanding of characteristics of multiple organ damage caused by rotaviral enteritis .Methods The clinical data of 68 cases diagnosed as the infection of rotaviral enteritis were retrospectively analyzed .The proportion of observed ap-pearance of multi-organ damage and fever ,acidosis were used as grouping criteria to analyze the relationship with CK-MB abnormalities.Results In 68 cases,including 46 cases of the elevation of CKMB ,9 cases of ECG T wave abnor-malities,symptoms of respiratory tract infection occurred in 37 patients,10 cases of liver function damage symptoms and increase of ALT,37 cases of acidosis,6 cases with symptoms of kidney damage ,skin rashes in 3 cases,2 cases of non febrile convulsions;fever,acidosis and CKMB anomaly had obvious correlation （χ2 =4.390,4.271,all P 〈0.05 ） .Conclusion Rotaviral enteritis with apparent clinical injury of multiple organ is relatively common .The regu-lar treatments after symptoms are very effective and the prognosis is good .The activity of creatine kinase isoenzyme al-ways is abnormal when the patients have fever ,acidosis ,which suggests that the active control of temperature and cor-rection of acidosis may reduce myocardial injury . Key words: Rotavirus; Diarrhea; Organ damage; Creatine kinase isoenzyme MB

Nanomicelle Formulation Modifies The Pharmacokinetic Profiles and Cardiac Toxicity of Daunorubicin

Treatment with daunorubicin (DNR) in acute myeloid leukemia is moderately effective and associated with significant side effects, including cardiac toxicity. We recently developed a nanomicellar formulation of DNR that specifically targets acute myeloid leukemia stem cells. Pharmacokinetics analysis of free DNR, DNR in nanomicellar formulations was performed in Balb/c mice and Sprague-Dawley rats. Histochemical staining, caspase 3/7, troponin and creatine kinase MB isoenzyme were used to assess toxicity. Compared with free DNR, the nanomicellar formulations of DNR had less cardiotoxicity as evidenced by milder histopathological changes, lower caspase 3/7 activity in heart tissue (p = 0.002), lower plasma creatine kinase MB isoenzyme (p = 0.002) and troponin concentrations (p = 0.001) postinjection. The area under curve concentration of DNR in micelles increased by 31.9-fold in mice (p < 0.0001) and 22.0-fold higher in rats (p < 0.001). Leukemia stem cell-targeting micelles dramatically change the pharmacokinetics and reduce the cardiac toxicity of DNR, which may enable improved DNR-based treatment of acute myeloid leukemia.

Incretin attenuates diabetes-induced damage in rat cardiac tissue.

Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect.

Disease-specific guidelines for reporting adverse events for peripheral vascular medical devices

Disease-specific guidelines for reporting adverse events for peripheral vascular medical devices

Myocardial injury following aortic valve replacement for severe aortic stenosis: risk factor of postoperative myocardial injury and its impact on long-term outcomes.

BackgroundAs hypertrophied myocardium predisposes the patient to decreased tolerance to ischemia and increased reperfusion injury, myocardial protection is of utmost importance in patients undergoing aortic valve replacement (AVR) for severe aortic valve stenosis (AS).MethodsConsecutive 314 patients (mean age, 62.5±10.8 years; 143 females) with severe AS undergoing isolated AVR were included. Postoperative myocardial injury (PMI) was defined as 1) maximum postoperative creatinine kinase isoenzyme MB or troponin-I levels ≥10 times of reference, 2) postoperative low cardiac output syndrome or episodes of ventricular arrhythmia, or 3) left ventricular ejection fraction of less than 55% and decrease in left ventricle (LV) ejection fraction of more than 20% of the baseline value.ResultsThere were 90 patients (28.7%) who developed PMI. There were five cases of early death (1.6%), all of whom had PMI. On multivariable analysis, the use of histidine-tryptophan-ketoglutarate (HTK) solution instead of blood cardioplegia (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.63 to 5.77; p=0.001), greater LV mass (OR, 1.04; 95% CI, 1.01 to 1.07; p=0.007), and increased cardiac ischemic time (OR, 1.13; 95% CI, 1.05 to 1.22; p<0.001) were independent predictors for PMI. Patients who had PMI showed significantly inferior long-term survival than those without PMI (p=0.049).ConclusionPMI occurred in a considerable proportion of patients undergoing AVR for severe AS and was associated with poor long-term survival. HTK cardioplegia, higher LV mass, and longer cardiac ischemic duration were suggested as predictors of myocardial injury.

Metabolismo oxidativo e cardíaco de equinos submetidos a exercício de baixa intensidade antes e após suplementação com antioxidante

O presente estudo objetivou avaliar os marcadores cardíacos e de lipoperoxidação em equinos no teste de exercício de baixa intensidade e longa duração (TLD), antes e após a suplementação com vitamina E. Para tanto, foram utilizados 10 equinos, submetendo-os ao primeiro TLD, com carga de trabalho fundamentada no consumo máximo de oxigênio individual (VO2max). Em seguida, durante 59 dias, os equinos receberam vitamina E (dl-alfa-tocoferol) na dose diária de 1.000UI por via oral e, posteriormente, realizaram um segundo TLD com o mesmo protocolo do primeiro. As amostras de sangue foram colhidas para determinação do malondialdeído (MDA) plasmático, como índice de lipoperoxidação, da concentração sérica de troponina I cardíaca (cTnI) e da isoenzima MB da creatinoquinase (CK-MB) como marcadores cardíacos. Como efeito do exercício, não se observou aumento significativo de MDA nem de cTnI, mas sim da concentração sérica de CK-MB, sugerindo-se o estresse miocárdico. A suplementação foi capaz de amenizar a produção de espécies reativas de oxigênio, evidenciada pela menor concentração de MDA em todos os momentos avaliados, porém não causou efeito protetor no miocárdio. Concluiu-se que o exercício de baixa intensidade e longa duração promoveu estresse miocárdico em equinos de forma leve e a suplementação com vitamina E reduziu a lipoperoxidação.

Analysis on the risk factors for occurrence of electrical storm in percutaneous coronary intervention and its treatment

Objective To investigate the risk factors for occurrence of electrical storm in the patients with acute ST segment elevation myocardial infarction (STEMI) when treat them by percutaneous coronary intervention (PCI) and provide evidence for prospective treatment.Methods Collected the clinical data of 280 patients with STEMI and treated by PCI from January 2008 to December 2011,the patients with no less than twice spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) were classified to the electrical storm group and others were classified to control group.Results The number of patients with electrical storm is nineteen and the incidence rate is 6.8％.In early group (from January 2008 to December 2009),the number of patients with electrical storm is sixteen.In late group (from January 2010 to December 2011),the number of patients with electrical storm is three.The electrical storm group:The value of creatine kinase isoenzyme MB (CK-MB),the value of troponin I (TNI),right coronary artery being the infarction related artery (IRA),TIMI level,bradycardia and sustained hypotension in the electrical group are significantly higher than those of control group (P ＜ 0.05).Multiple logistic regression analysis showed that the independent predictors of VAS were the value of troponin I (TNI),TIMI level and sustained hypotension.Conclusions The value of creatine kinase isoenzyme MB (CK-MB),the value of troponin I (TNI),right coronary artery being the infarction related artery (IRA),TIMI level,bradycardia and sustained hypotension are the risk factors for occurrence of electrical storm.the value of troponin I (TNI),TIMI level and sustained hypotension were stronger predictors of electrical storm.Early treatment to the risk factors can reduce the incidence of VAS,and improve the prognosis. Key words: Myocardial infarction; Percutaneous coronary angioplasty; Ventricular arrhythmia storms ; Risk factors; Treatment

Apelin-12 and its structural analog enhance antioxidant defense in experimental myocardial ischemia and reperfusion.

This study investigated the effects of peptide apelin-12 (H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH, A12) and its novel structural analog (H-(NαMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, AI) on myocardial antioxidant enzyme activities, lipid peroxidation, and reactive oxygen species formation in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury. Isolated working rat hearts were subjected to global ischemia and reperfusion. Infusion of 140 μM A12 or AI before global ischemia improved cardiac function recovery; increased the activity of Cu,Zn superoxide dismutase (Cu,Zn SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); decreased malondialdehyde (MDA) content in reperfused heart; and reduced the formation of hydroxyl radical adduct of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide in the myocardial effluent during early reperfusion compared with these indices in control. Anesthetized open-chest rats were subjected to the left anterior descending coronary artery occlusion and coronary reperfusion. Peptide A12 or its analog AI was injected intravenously at the onset of reperfusion at a dose of 0.35 μmol/kg. Treatment with A12 or AI significantly limited infarct size and reduced the activity of lactate dehydrogenase and creatine kinase MB isoenzyme in blood plasma at the end of reperfusion compared with control. These effects were accompanied by complete recovery of Cu,Zn SOD, CAT, and GSH-Px activities; and decrease in MDA content in the area at risk by the end of reperfusion. The study concluded that C-terminal fragment of native peptide apelin-12 and its synthesized analog is involved in the upregulation of cardiac antioxidant defense systems and attenuation of lipid peroxidation in myocardial I/R injury.

The protection of the Caspase-3 inhibitor on cardiopulmonary bypass-induced cardiac function injury in the rabbit model

Objective To investigate the protection of the Caspase-3 inhibitor (Ac-DEVD-CHO) on cardiopulmonary bypass (CPB)-induced ischemia reperfusion injury in the rabbit model.Methods Rabbits were divided into two groups:control (C) group and Ac-DEVD-CHO (A) group.In the C and A groups,animals underwent CPB at a flow rate of 50-70 ml/kg per min,Ac-DEVD-CHO (5 ml/kg) was administered to the A group rabbits by intravenous injection 30 min before operation and Ac-DEVD-CHO (5 ml/kg) was administered by intravenous infusion while reperfusion being done.The myeloperoxidase (MPO) and Caspase-3 activity,the blood creatine kinase isoenzyme MB (CK-MB) and cardiac troponin Ⅰ (cTnⅠ) in each group were detected.Results A comparison between A group and C group showed that for treated group,the levels of CK-MB (U/L) (111.39 ± 0.03,134.26 ± 3.45,342.49 ± 5.35,501.25 ±8.31 vs.100.41 ± 0.02,435.21 ± 6.38,987.32 ± 25.17,1 264.53 ± 22.08) and cTnⅠ (g/L) (0.03 ±0.02,0.03±0.06,0.08±0.04,0.09±0.02 vs.0.03 ±0.01,0.06±0.03,0.12±0.05,0.17±0.07)were both decreased,the activity of Caspase-3 (z/pmol/h/mg) (0.03 ±0.01,0.09 ±0.02,0.18 ±0.03,0.39±0.02 vs.0.02±0.01,0.16 ±0.05,0.72 ±0.04,0.87 ±0.06) and MPO(μg/L) (0.33±0.02,0.53 ±0.03,0.67 ±0.03,0.88 ±0.05 vs.0.33 ± 0.01,0.96 ±0.04,1.12 ±0.03,2.17 ±0.02) were inhibited (F =36.10-574.13,P ＜ 0.05).The differences of the above items were of statistically significant.Conclusion Ac-DEVD-CHO inhibited the changes in the MPO and Caspase-3 activity and decreased the blood CK-MB and cTnⅠ in simulated extracorporeal circulation.This study suggests that Ac-DEVD-CHO could be feasible therapeutic strategy to protect the cardiac function injury in patients undergoing cardiopulmonary bypass. Key words: The Caspase-3 inhibitor; Cardiopulmonary bypass; Creatine kinase isoenzyme MB ; Cardiac troponin Ⅰ ; Caspase-3 activity ; Myeloperoxidase

Rapid Identification of Falsely Elevated Serum Cardiac Troponin I Values in a Stat Laboratory

To establish a rapid method for the stat laboratory to identify falsely elevated serum cardiac troponin I (cTnl) values caused by endogenous interferences. Serum specimens with elevated cTnI were recentrifuged and cTnI was measured again. If the difference between first and second cTnI value was less than +/- 30%, the specimen was diluted 1:2, 1:5, and 1:10, and the cTnI was measured in the diluted specimens. If the cTnI concentrations did not change linearly with dilution, the specimen was referred to an outside lab for re-analysis of cTnI by a different immunochemical method. Troponin I was elevated in 132 serum specimens. In 18 specimens, we attributed the elevation to the presence of fibrin or microparticles in the serum. Serial dilutions of 3 of the 114 remaining specimens produced nonlinear results. Overall, falsely elevated cTnI results were identified in 1.01% of all measurements. Our method, which uses combined measurement of cTnI, creatinine kinase MB isoenzyme (CK-MB), and myoglobin, together with incubation, re-centrifugation, and serial dilution, is a practical method to identify falsely elevated serum cTnI values.

Inhibition of Gene Expression of Carnitine Palmitoyltransferase I and Heart Fatty Acid Binding Protein in Cyclophosphamide and Ifosfamide-Induced Acute Cardiotoxic Rat Models

This study investigated whether cyclophosphamide (CP) and ifosfamide (IFO) therapy alters the expression of the key genes engaged in long-chain fatty acid (LCFA) oxidation outside rat heart mitochondria, and if so, whether these alterations should be viewed as a mechanism during CP- and IFO-induced cardiotoxicity. Adult male Wistar albino rats were assigned to one of the six treatment groups: Rats in group 1 (control) and group 2 (L-carnitine) were injected intraperitoneal (i.p.) with normal saline and L-carnitine (200mg/kg/day), respectively, for 10 successive days. Animals in group 3 (CP group) were injected i.p. with normal saline for 5days before and 5days after a single dose of CP (200mg/kg, i.p.). Rats in group 4 (IFO group) received normal saline for 5 successive days followed by IFO (50mg/kg/day, i.p.) for 5 successive days. Rats in group 5 (CP-carnitine supplemented) were given the same doses of L-carnitine as group 2 for 5days before and 5days after a single dose of CP as group 3. Rats in group 6 (IFO-carnitine supplemented) were given the same doses of L-carnitine as group 2 for 5days before and 5days concomitant with IFO as group 4. Immediately, after the last dose of the treatment protocol, blood samples were withdrawn and animals were killed for biochemical, histopathological and gene expression studies. Treatment with CP and IFO significantly decreased expression of heart fatty acid binding protein (H-FABP) and carnitine palmitoyltransferase I (CPT I) genes in cardiac tissues. Moreover, CP but not IFO significantly increased acetyl-CoA carboxylase2 mRNA expression. Conversely, IFO but not CP significantly decreased mRNA expression of malonyl-CoA decarboxylase. Both CP and IFO significantly increased serum lactate dehydrogenase, creatine kinase isoenzyme MB and malonyl-CoA content and histopathological lesions in cardiac tissues. Interestingly, carnitine supplementation completely reversed all the biochemical, histopathological and gene expression changes induced by CP and IFO to the control values, except CPT I mRNA, and protein expression remained inhibited by IFO. Data from the current study suggest, for the first time, that (1) CP and IFO therapy is associated with the inhibition of the expression of H-FABP and CPT I genes in cardiac tissues with the consequent inhibition of mitochondrial transport and oxidation of LCFA. (2) The progressive increase in cardiotoxicity enzymatic indices and the decrease in H-FABP and CPT I expression may point to the possible contribution of these genes to CP- and IFO-induced cardiotoxicity.