Creatine kinase-MB Activity Research Articles

Effect of dexmedetomidine on myocardial injury in infants undergoing repair of ventricular septal defect

Objective To evaluate the effect of dexmedetomidine on myocardial injury in infants undergoing repair of ventricular septal defect.Methods Forty ASA grade Ⅱ or Ⅲ infants,aged 3-6 months,weighing 4-6 kg,scheduled for elective repair of ventricular septal defect,were randomly divided into 2 groups (n =20each):control group (group C) and dexmedetomidine group (group D).Anesthesia was induced with midazolam,etomidate,cisatracurium and sufenanil.The infants were mechanically ventilated after nasotracheal intubation.PET CO2 was maintained at 30-40 mm Hg,Anesthesia was maintained with cisatracurium,sufenanil and sevoflurane.In group D,dexmedetomidine was infused at 0.5 μg· kg-1 · h-1 until the end of operation.While in group C normal saline was given at the same rate until the end of operation.BP and HR were recorded at 10 min before operation (T1),skin incision (T2),chest opening (T3),10 min after aortic unclamping (T4) and the end of operation (T5).Blood samples were taken from the right internal jugular vein for determination of plasma creatine kinase MB (CK-MB) activity and cardiac troponin T (cTnT) concentrations at T1,T5 and 24 h after operation (T6).Results Compared with the baseline value at T1,no significant changes were found in HR and BP at different time points in group D,HR and BP were significanfly increased at T2-T5 in group C,and the plasma CK-MB ctivity and cTnT concentration were significantly increased at T5 and T6 in the two groups (P ＜ 0.05).HR and BP at T2-5 and plasma CK-MB activity and cTnT concentration at T5 and T6 were significantly lower in group D than in group C (P ＜0.05).Conclusion Dexmedetomidine infused at 0.5 μg· kg-1 · h-1 after induction can reduce myocardial injury in infants undergoing repair of ventricular septal defect. Key words: Dexmedetomidine ; Heart septal defects, ventricular; Infant ; Myocardial reperfusion injury

Inhibition of JNK Mitochondrial Localization and Signaling Is Protective against Ischemia/Reperfusion Injury in Rats

To build upon recent findings that mitochondrial JNK signaling is inhibited by selectively blocking the interaction between JNK and Sab, we utilized a cell-permeable peptide to demonstrate that ischemia/reperfusion (I/R) injury could be protected in vivo and that JNK mitochondrial signaling was the mechanism by which reactive oxygen species (ROS) generation, mitochondrial dysfunction, and cardiomyocyte cell death occur. We also demonstrated that 5 mg/kg SR-3306 (a selective JNK inhibitor) was able to protect against I/R injury, reducing infarct volume by 34% (p < 0.05) while also decreasing I/R-induced increases in the activity of creatine phosphokinase and creatine kinase-MB. TUNEL staining showed that the percent TUNEL positive nuclei in rat hearts increased 10-fold after I/R injury and that this was reduced 4-fold (p < 0.01) by SR-3306. These data suggest that blocking JNK mitochondrial translocation or JNK inhibition prevents ROS increases and mitochondrial dysfunction and may be an effective treatment for I/R-induced cardiomyocyte death.

Clinical Evaluation of a New Creatine Kinase MB Activity Reagent Abrogating the Effect of Mitochondrial Creatine Kinase

Measuring creatine kinase (CK) MB activity using the immunoinhibition method remains useful in clinical laboratories. CK-MB activity is abnormally high when macro CK type 2 (mitochondrial creatine kinase, MtCK) is present in patient serum. In order to improve the accuracy of the CK-MB activity assay, we developed a new CK-MB activity method using highly specific anti-MtCK antibodies. We evaluated the clinical performance of the new method, which abrogates the effect of MtCK activity. Receiver operating characteristic analysis, CK-MB activity range, cut-off, and CK-MB to CK activity ratio were investigated. Mean CK-MB activity in normal human serum was 2.5 U/L by our method, in contrast to 12.0 U/L by the current method. Approximately 80% of CK-MB activity determined using the current kit corresponds to MtCK activity, and ubiquitous mitochondrial creatine kinase activity constitutes approximately 90% of MtCK activity. The cut-off and CK-MB activity ratio of our method were 12 U/L and 3 to 20%, respectively, in contrast to 22 U/L and 5 to 23%, respectively, using the current CK-MB method. The areas under the curve of our method, current CK-MB, electrophoresis, and CK-MB mass were 0.976, 0.928, 0.967, and 0.991, respectively. Our new method was superior to the electrophoresis and CK-MB mass as well as the conventional method due to jts promptness, simplification, and low cost. The new kit will improve the clinical diagnosis of acute myocardial infarction. CK-MB activity assay was considered as a suitable alternative to conventional cardiac markers due to its superior diagnostic validity.

Biocompatible Microemulsion Modifies the Pharmacokinetic Profile and Cardiotoxicity of Doxorubicin

Doxorubicin (DOX) is an anthracycline antibiotic with a broad antitumor spectrum. However, the clinical use of DOX is limited because of its cardiotoxicity, a dose-dependent effect. Colloidal drug delivery systems, such as microemulsions (MEs), allow the incorporation of drugs, modifying the pharmacokinetic (PK) profile and toxic effects. In this study, we evaluated the PK profile and cardiotoxicity of a new DOX ME (DOX-ME). The PK profile of DOX-ME was determined and compared with that of the conventional DOX after single-dose administration (6 mg/kg, intravenous) in male Wistar rats (n = 12 per group). The cardiotoxicity of DOX formulations was evaluated by serum creatine kinase MB (CKMB) activity in both animal groups before and after drug administration. The plasma DOX measurements were performed by high-performance liquid chromatography with fluorescence detection, and the CKMB levels were assayed using the CKMB Labtest® kit. The ME system showed a significant increase in plasma DOX concentrations and lower distribution volume when compared with conventional DOX. Serum CKMB activity increased after conventional DOX administration but was unchanged in the DOX-ME group. These results demonstrate modifications in drug access to susceptible sites using DOX-ME. DOX-ME displayed features that make it a promising system for future therapeutic application.

Protective Effects of Shen-Yuan-Dan, a Traditional Chinese Medicine, against Myocardial Ischemia/Reperfusion InjuryIn VivoandIn Vitro

Objectives. The study was to investigate the effects and mechanisms of Shen-Yuan-Dan (SYD) pharmacological postconditioning on myocardial ischemia/reperfusion (I/R) injury. Methods. In the in vivo experiment, myocardial injury markers and histopathology staining were examined. In the in vitro experiment, cell viability and cell apoptosis were, respectively, detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and Hoechst 33342 fluorochrome staining. The protein expressions of Bcl-2 and Bax were determined by immunocytochemistry assay. Results. Both low and high doses of SYD protected myocardium against I/R injury in rat model by reducing lactic dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity and malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activity and attenuating histopathology injury. Meanwhile, in the in vitro experiment, SYD promoted cell viability and inhibited the cardiomyocyte apoptosis. The level of Bcl-2 protein was restored to the normal level by SYD pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by SYD pharmacological postconditioning. These effects of SYD were inhibited by LY294002. Conclusions. The results of this study suggested that SYD pharmacological postconditioning has protective effects against myocardial I/R injury in both in vivo and in vitro models, which are related to activating the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway.

Anti-inflammatory Effect of Protocatechuic Aldehyde on Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro

Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response plays a vital role, is frequently encountered in clinical practice. The present study was aimed to investigate the anti-inflammatory effect and the possible mechanism of protocatechuic aldehyde (PAl) on MI/R injury both in vivo and in vitro. The rat model of MI/R injury was induced by ligation of the left anterior descending coronary artery for 30 min, followed by 3-h reperfusion, and pretreatment with PAl could protect the heart from MI/R injury by reducing myocardial infarct size and the activities of creatine kinase-MB and cardiac troponin I (cTn-I) in serum. Also, PAl administration markedly reduced cellular injury induced by simulated ischemia/reperfusion (SI/R) in cultured neonatal rat cardiomyocytes, which was evidenced by increased cell viability, reduced lactate dehydrogenase and cTn-I activities in the culture medium, and greatly decreased percentage of cell apoptosis. Moreover, the levels of tumor necrosis factor-α, interleukin-6, intracellular adhesion molecule-1, phosphorylated IκB-α, and the nuclear translocation of nuclear factor-kappa B (NF-κB) were all evidently decreased by PAl both in vivo and in vitro. Taken together, these observations suggested that PAl could exert great protective effects against MI/R injury in rats and SI/R injury in cultured neonatal rat cardiomyocytes, and the cardioprotective mechanism might be involved in the suppression of inflammatory response via inhibiting the NF-κB signaling pathway.

Elevated Serum Cardiac Troponin I in Cattle with Theileriosis

Theileria annulata is a blood parasite affecting ruminants. Hemolytic anemia, secondary hypoxia, and vasculitis are the most important features of tropical theileriosis. Evaluation of electrocardiographic findings and changes in cardiovascular biochemical markers including cTnI concentrations in cattle naturally infected with theileriosis in the absence of acute cardiac failure. Ninety adult Holstein cattle (>1 year) with clinical and laboratory evidence of theileriosis and 30 healthy cattle served as controls. Case-control study in which blood samples were collected and randomized after clinical, hematologic, parasitologic examination and laboratory confirmation and electrocardiographic recording on all animals, serum cardiac troponin I (cTnI), aspartate aminotransferase (AST), and creatine kinase-MB (CK-MB) were evaluated. Serum concentration of cTnI was significantly higher in cattle with theileriosis (mean: 0.028 ng/mL; range: 0.005-0.21 ng/mL; control mean: 0.011; range: <0.005-0.09 ng/mL; P = .003). There was significant correlation between serum level of cTnI and PCV (r = -0.257; P < .001) and also between cTnI and parasitemia (r = 0.515; P < .001). Mean serum activities of AST and CK-MB were 107 ± 46 and 301 ± 103 U/L in sick animals, which were significantly higher than healthy cattle (P = .002 and P = .041, respectively). There were no pathologic arrhythmias detected in sick animals. Theileriosis is a risk factor for elevation of cardiac biomarkers in naturally infected Holstein cattle. Severity of anemia and parasitemia might contribute to the pathophysiology of myocardial damage. The prognostic significance of increased serum cardiac troponin I concentrations in cattle with hemolytic anemia merits further investigation.

Effects of sevoflurane pretreatment on inflammatory response in patients undergoing cardiac valve replacement with cardiopulmonary bypass

Objective To investigate the effects of sevoflurane pretreatment on the inflammatory response in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB) and the mechanism of myocardial protection.Methods Twenty NYHA class Ⅱ or Ⅲ patients of both sexes,aged ＜ 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n=10 each): sevoflurane group (group S) and control group (group C).The patients were premedicated with intramuscular morphine 0.1 mg/kg and scopolamine 0.3 mg.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.The patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with intermittent iv boluses of midazolam0.03-0.06 mg/kg,fentanyl 5-10μg/kg and pipecuronium 0.04-0.08 mg/kg.Sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly adjusted to 1.0％ and maintained at this level for 30 min in group S.Blood samples were taken from the central vein before skin incision,immediately after aortic clamping,immediately after aortic unclamping and at 30 min after aortic unclamping,at 2,6,12 and 24 h (T1-8) after operation for determination of the concentrations of plasma tumor necrosis factor-α (TNF-α),interleukin-6 (IL) and interleukin-8 (IL-8),intercellular adhesion molecule-1 (ICAM-1),cardiac troponin I (cTnI) and activity of creatine kinase MB (CK-MB).The requirement for cardiovascular drugs was recorded after release of aortic cross clamp.Results Compared with group C,the plasma concentrations of TNF-α,IL-6 and IL-8 were significantly decreased at T3-8,the plasma concentrations of ICAM-1 and cTnl were significantly decreased at T4-8,the activity of plasma CK-MB was significantly decreased at T8,and the requirement for cardiovascular drugs was significantly reduced after release of aortic cross clamp in group S (P ＜0.05).Conclusion Sevoflurane pretreatment can inhibit the inflammatory response and provide myocardial protection to some extent in patients undergoing cardiac valve replacement with CPB. Key words: Anesthetics,inhalation; Cardiopulmonary bypass; Myocardial; Inflammation

Protective effects of magnesium supplementation on metabolic energy derangements in lipopolysaccharide-induced cardiotoxicity in mice

Metabolic derangements and bioenergetic failure are major contributors to sepsis-induced multiple organ dysfunctions. Due to the well known role of magnesium (Mg) as a cofactor in many enzymatic reactions that involve energy creation and utilization, the present investigation was directed to estimate the cardioprotective effect of Mg supplementation in lipopolysaccharide (LPS)-induced metabolic energy changes in mice. Oral doses of Mg aspartate (20 or 40mg/kg) were administered once daily for 7day. Mice were then subjected to a single intraperitoneal injection of LPS (2mg/kg). Plasma was separated 3h after LPS injection for determination of creatine kinase-MB activity. Animals were then sacrificed and the hearts were separated for estimation of tissue thiobarbituric acid reactive substances, reduced glutathione, lactate, pyruvate, adenine nucleotides, creatine phosphate and cardiac Na+,K+-ATPase activity. Finally, electron microscopic examination was performed to visualize the protective effects of Mg pretreatment on mitochondrial ultrastructure. In general, the higher dose of Mg was more effective than the lower dose in ameliorating creatine kinase-MB elevation and the state of oxidative stress, lactate accumulation, pyruvate reduction as well as preserving creatine phosphate, adenine nucleotides and Na+,K+-ATPase activity. Moreover, the higher dose of Mg provided a significant cardioprotection against the mitochondrial ultrastructural changes. Mg therapy can afford a significant protection against metabolic energy derangements and mitochondrial ultrastructural changes induced by LPS cardiotoxicity in mice.

Protective effects of thymol on altered plasma lipid peroxidation and nonenzymic antioxidants in isoproterenol‐induced myocardial infarcted rats

This study evaluates the protective effects of thymol on altered plasma lipid peroxidation products and nonenzymic antioxidants in isoproterenol (ISO)-induced myocardial infarcted rats. Male albino Wistar rats were pre and cotreated with thymol (7.5 mg/kg body weight) daily for 7 days. ISO (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce myocardial infarction (MI). Increased activity/levels of serum creatine kinase-MB (CK-MB), plasma thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes with decreased levels of plasma reduced glutathione (GSH), vitamin C, and vitamin E were observed in ISO-induced myocardial infarcted rats. Pre and cotreatment with thymol (7.5 mg/kg body weight) showed normalized activity of serum CK-MB and near normalized levels of plasma lipid peroxidation products, reduced GSH, vitamin C, and vitamin E in myocardial infarcted rats. Furthermore, the in vitro study on reducing power of thymol confirmed its potent antioxidant action. Thus, thymol protects ISO-induced MI in rats by its antilipid peroxidation and antioxidant properties.

Cardioprotective effects of ozone oxidative preconditioning in an in vivo model of ischemia/reperfusion injury in rats

Background. Several studies have demonstrated the beneficial effects of ozone oxidative preconditioning in several pathologies characterized by cellular oxidative and inflammatory burden. The present study was designed to investigate the cardioprotective effects of oxidative preconditioning in ischemia/reperfusion (I/R) injury. Methods. Rats were randomly assigned into five groups. Groups 1 and 2 were normal and I/R groups, respectively. Two of the other groups received two different doses of ozone therapies by rectal insufflations. The last group received vehicle (oxygen). Rats were subjected to myocardial I/R (40min/10min). Heart rate and ventricular arrhythmias were recorded during I/R progress. At the end of reperfusion, plasma creatine kinase-MB (CK-MB) activity and total nitrate/nitrite (NOx) were determined. In addition, lactate, adenine nucleotides, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and myeloperoxidase (MPO) activity were estimated in the heart left ventricle. Histological examination was also performed to visualize the protective cellular effects. Results. Both doses of ozone therapy were equally protective in reducing CK-MB release. However, the higher dose was more effective in reducing oxidative stress, lactate accumulation, elevated MPO activity and plasma NOx as well as preserving myocardial adenine nucleotides. Histological examination also revealed better improvement with a higher dose of ozone therapy compared to the I/R group. Conclusion. Ozone therapy can afford significant cardioprotection against biochemical and histological changes associated with I/R injury.

Effect of ginsenoside Rh1 on myocardial injury and heart function in isoproterenol-induced cardiotoxicity in rats

The present study was designed to investigate the effect of ginsenoside Rh1 on myocardial injury and heart function in isoproterenol-induced cardiotoxicity in rats. Sprague–Dawley rats were subcutaneously injected with isoproterenol (20 mg/kg). Cardiac marker enzymes in serum, antioxidative parameters and inflammatory cytokines in left ventricles were measured. Hemodynamic parameters were monitored and recorded as well. Histopathological examination of left ventricles was performed. It was found that creatine kinase-MB (CK-MB) activity and troponin T level in isoproterenol-treated rats were significantly increased. Isoproterenol caused declines of left ventricular systolic pressure, positive and negative maximal values of the first derivative of left ventricular pressure, and an elevation of left ventricular end diastolic pressure. Isoproterenol enhanced the content of malondialdehyde (MDA), tumor necrosis-α (TNF-α), interleukin-1β (IL-1β) and decreased the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) in left ventricles. Ginsenoside Rh1 significantly ameliorated myocardial injury and heart function impairment induced by isoproterenol. The cardioprotective effect of ginsenoside Rh1 was further confirmed by histopathological examination. Ginsenoside Rh1 also partially inhibited the increase of MDA, TNF-α, IL-1β contents and the decrease of SOD, catalase, and GSH-Px activities in left ventricles. The results indicated that ginsenoside Rh1 possessed the effect against isoproterenol-induced cardiotoxicity, and that the mechanism of pharmacological action was related to regulating the activities of SOD, catalase, and GSH-Px and decreasing the contents of TNF-α and IL-1β.

Lycopene attenuates oxidative stress and heart lysosomal damage in isoproterenol induced cardiotoxicity in rats: A biochemical study

The present study was designed to investigate the cardioprotective potential of lycopene (LYC) on isoproterenol (ISO)-induced oxidative stress and heart lysosomal damage in rats. Male Sprague Dawley rats were pretreated with LYC (4mg/kg, p.o.) once daily for 21 days. After the treatment period, ISO (85mg/kg) was injected subcutaneously, once daily, to rats for 2 days. Hemodynamic parameters, cardiac marker enzymes, antioxidant, and oxidative stress parameters in serum and heart tissues were measured. ISO treated rats showed significant changes in heart rates, heart weights and serum lipid profiles. The activity of aspartate aminotranferase (AST), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) were increased significantly (p<0.01) in the serum of ISO rats. The levels of lipid peroxides (thiobarbituric acid reactive substances, TBARS), protein carbonyl content (PCC) and neutrophil infiltration marker; myeloperoxidase (MPO) were significantly (p<0.01) increased. In addition, the activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetylglucosaminidase, and cathepsin-d) in the serum and heart of ISO rats were increased significantly. Furthermore, a marked decrease in the levels of serum and cardiac reduced glutathione (GSH), vitamin C and cardiac enzymatic antioxidants; superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were observed. In vitro study confirmed the strong antioxidant effect of LYC on total antioxidant activity. In conclusion, the present study demonstrated that LYC supplementation to ISO rats significantly ameliorated lysosomal membrane damage as well as the alterations in cardiac enzymes, lipid profile and oxidative stress markers. These findings revealed the cardioprotective effects of LYC against ISO-induced oxidative stress and cardiotoxicity in rats. These observed effects are mediated via antioxidant power and free radical scavenging activity of LYC.

Metabolic and cardiac signaling effects of inhaled hydrogen sulfide and low oxygen in male rats

Low concentrations of inhaled hydrogen sulfide (H(2)S) induce hypometabolism in mice. Biological effects of H(2)S in in vitro systems are augmented by lowering O(2) tension. Based on this, we hypothesized that reduced O(2) tension would increase H(2)S-mediated hypometabolism in vivo. To test this, male Sprague-Dawley rats were exposed to 80 ppm H(2)S at 21% O(2) or 10.5% O(2) for 6 h followed by 1 h recovery at room air. Rats exposed to H(2)S in 10.5% O(2) had significantly decreased body temperature and respiration compared with preexposure levels. Heart rate was decreased by H(2)S administered under both O(2) levels and did not return to preexposure levels after 1 h recovery. Inhaled H(2)S caused epithelial exfoliation in the lungs and increased plasma creatine kinase-MB activity. The effect of inhaled H(2)S on prosurvival signaling was also measured in heart and liver. H(2)S in 21% O(2) increased Akt-P(Ser473) and GSK-3β-P(Ser9) in the heart whereas phosphorylation was decreased by H(2)S in 10.5% O(2), indicating O(2) dependence in regulating cardiac signaling pathways. Inhaled H(2)S and low O(2) had no effect on liver Akt. In summary, we found that lower O(2) was needed for H(2)S-dependent hypometabolism in rats compared with previous findings in mice. This highlights the possibility of species differences in physiological responses to H(2)S. Inhaled H(2)S exposure also caused tissue injury to the lung and heart, which raises concerns about the therapeutic safety of inhaled H(2)S. In conclusion, these findings demonstrate the importance of O(2) in influencing physiological and signaling effects of H(2)S in mammalian systems.

Effect of ursolic acid treatment on apoptosis and DNA damage in isoproterenol-induced myocardial infarction

The present study was designed to evaluate the protective effect of ursolic acid (UA) against isoproterenol-induced myocardial infarction. Myocardial infarction was induced by subcutaneous injection of isoproterenol hydrochloride (ISO) (85 mg/kg BW), for two consecutive days. ISO-induced rats showed elevated levels of cardiac troponins T (cTn T) and I (cTn I) and increased activity of creatine kinase-MB (CK-MB) in serum. Lipid peroxidative markers (thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (HP)) elevated in the plasma and heart tissue whereas decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)) in erythrocytes and heart tissue of ISO-induced rats. Non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione (GSH)) levels were decreased significantly in the plasma and heart tissue of ISO-induced rats. Furthermore, ISO-induced rats showed increased DNA fragmentation, upregulations of myocardial pro-apoptotic B-cell lymphoma-2 associated-x (Bax), caspase-3, -8 and -9, cytochrome c, tumor necrosis factor-α (TNF-α), Fas and down-regulated expressions of anti-apoptotic B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL). UA-administered rats showed decreased levels/activity of cardiac markers, DNA fragmentation and the levels of lipid peroxidative markers in the plasma and heart tissue. Activities of enzymatic antioxidants were increased significantly in the erythrocytes and heart tissue and also non-enzymatic antioxidants levels were increased significantly in the plasma and heart tissue in UA-administered rats. UA influenced decreased DNA fragmentation and an apoptosis by upregulation of anti-apoptotic proteins such as Bcl-2, Bcl-xL and down-regulation of Bax, caspase-3, -8 and -9, cytochrome c, TNF-α, Fas through mitochondrial pathway. Histopathological observations were also found in line with biochemical parameters. Thus, results of the present study demonstrated that the UA has anti-apoptotic properties in ISO-induced rats.

Preventive effects of N-acetyl cysteine on lipids, lipoproteins and myocardial infarct size in isoproterenol induced myocardial infarcted rats: An in vivo and in vitro study

The present study evaluated the preventive effects of N-acetyl cysteine in isoproterenol induced myocardial infarcted rats. Rats were pretreated with N-acetyl cysteine (10mg/kg body weight) daily for a period of 14days. After pretreatment, rats were injected with isoproterenol (100mg/kg body weight) at an interval of 24h for two days to induce myocardial infarction. Isoproterenol induced myocardial infarction was indicated by increased activity of creatine kinase-MB and levels of cardiac troponins in the serum. The weight of heart and the levels of serum and heart cholesterol, triglycerides, free fatty acids were increased in isoproterenol induced myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased high density lipoprotein cholesterol. It enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase and the levels of lipid peroxidation products. Pretreatment with N-acetyl cysteine showed significant preventive effects in all the biochemical parameters studied in myocardial infarcted rats. Also, N-acetyl cysteine reduced myocardial infarct size. Histopathological findings of N-acetyl cysteine pretreated myocardial infarcted heart correlated with these biochemical findings. The in vitro study confirmed the strong antioxidant action of N-acetyl cysteine. Thus, the present study revealed that N-acetyl cysteine prevented increased heart weight, accumulation of lipids, altered levels of lipoproteins thereby reducing myocardial infarct size due to its antilipidemic and antioxidant effects in isoproterenol induced myocardial infarcted rats. This study may have a significant impact on myocardial infarction.

Comparative study of the cardioprotective effects of local and remote preconditioning in ischemia/reperfusion injury

AimsThough the cardioprotective effects of local or remote preconditioning have been estimated, it is still unclear which of them is more reliable and provides more cardioprotection. The present investigation was directed to compare, in one study, the cardioprotective effects of different cycles of local or remote preconditioning in ischemia/reperfusion (I/R)-induced electrophysiological, biochemical and histological changes in rats. Main methodsRats were randomly assigned into 10 groups. Groups 1 and 2 were normal and I/R groups, respectively. Other groups were subjected to 1, 2, 3, 4 cycles of local or remote preconditioning before myocardial I/R (40min/10min). Heart rate and ventricular arrhythmias were recorded during I/R progress. At the end of reperfusion, plasma creatine kinase-MB (CK-MB) activity and total nitrate/nitrite (NOx) were determined. In addition, lactate, adenine nucleotides, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and myeloperoxidase (MPO) activity were estimated in the heart left ventricle. Histological examination was also performed to visualize the protective cellular effects of the effective cycle of local or remote preconditioning. Key findingsIn general, local preconditioning was more effective than remote preconditioning in reducing ventricular arrhythmias, CK-MB release, lactate accumulation and elevated MPO activity as well as preserving adenine nucleotides. Concerning the most effective group in each therapy, 3 cycles of local preconditioning provided more cardioprotection than that of remote preconditioning in the histological examination. SignificanceDespite being invasive, local preconditioning provided more effective cardioprotection than remote preconditioning in ameliorating the overall electrophysiological, biochemical and histological changes.

Effects of sevoflurane wash-in during cardiopulmonary bypass on myocardial injury in patients undergoing coronary artery bypass grafting

Objective To investigate the effects of sevoflurane wash-in during cardiopulmonary bypass (CPB) on myocardial injury in patients undergoing coronary artery bypass grafting(CABG).Methods Forty ASA Ⅱ or Ⅲ patients aged 50-64 yr,weighing 53-90 kg undergoing scheduled for CABG under CPB were randomly divided into 2 groups (n =20): control group (group C) and sevoflurane group(group S).Anesthesia was maintained with propofol 3-5 mg·kg-1 ·h-1 and sufentanil 0.5-1.0 μg·kg-1 ·h-1 in both groups.Sevoflurane 1％-2％ was washed into extracorporeal circuit during CPB in group S.Blood samples were taken from central vein after the induction of anesthesia (T0,baseline) and at 6,12 and 24 h (T1-3) after operation for determination of plasma cardiac troponin I(cTnI) concentration and creatine kinase-MB (CK-MB) activity.Myocardial specimens were obtained from right auricle before aortic cross-clamping and at the end of CPB for ultrastructure examination.The severity of mitochondria injury was assessment and scored (0 =normal,4 =impaired inner mitochondrial membrane integrity).Results CPB significantly increased plasma cTnI concentration at T1-3 as compared with the baseline values at T0 before CPB.Plasma cTnI concentration was significantly lower at T2 and T3 in group S than in group C.Mitochondrial injury index was significantly lower at the end of CPB in group S than in group C.There was no significant difference in plasma CK-MB activity between the 2 groups.Conclusion Wash-in of sevoflurane during CPB can attenuate myocardial injury in patients undergoing CABG. Key words: Anesthetics, inhalation; Myocardial reperfusion injury; Cardiopulmonary bypass; Coronary artery bypass graft

Cardioprotective Effects of an Aminothiazole Compound on Isoproterenol-Induced Myocardial Injury in Mice

Dendrodoine analogue (DA), an aminothiazole compound derived from dendrodoine, present in a marine tunicate, has been shown to possess many beneficial properties. This study was aimed to evaluate its cardioprotective effect against isoproterenol (ISO)-induced myocardial damage in mice. Swiss mice were pretreated with DA for 7days and then treated with ISO (5mg/kg BW, for 2 consecutive days). Biochemical assessment of myocardial injury was carried out by measuring marker enzymes, antioxidant enzymes and levels of lipid peroxidation. Histological studies of hearts were also carried out. ISO administration increased the activities of creatine kinase-MB, lactate dehydrogenase and aspartate aminotranferase (AST) in serum. Prior administration of DA restored the levels of these enzymes and the heart coefficient close to normal levels. DA at a concentration of 5mg/kg BW was most effective in reducing AST, and this concentration was used for further studies. DA also gave significant protection against lipid peroxidation in the heart besides restoring histopathological alterations. DA showed significant reactivity towards superoxide radicals. In conclusion our study indicates that DA can protect mouse myocardium against damage and one of the possible reasons behind this protective effect can be attributed to its antioxidant property.

A biochemical, electrocardiographic, electrophoretic, histopathological and in vitro study on the protective effects of (−)epicatechin in isoproterenol-induced myocardial infarcted rats

(-) Epicatechin rich foods and (-) epicatechin improve cardiovascular function. Consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular diseases. Oxidative stress resulting from increased production of free radicals associated with decreased levels of antioxidants in the myocardium plays a major role in the pathogenesis of myocardial infarction. This study aims to evaluate the preventive effects of (-) epicatechin on oxidative stress in isoproterenol-induced myocardial infarcted rats. Male Wistar rats were pretreated with (-) epicatechin (20mg/kg body weight) daily for 21 days. After pretreatment, isoproterenol (100mg/kg body weight) was injected into the rats at an interval of 24h for two days to induce myocardial infarction. Isoproterenol induced rat's electrocardiogram showed elevated ST segments and significant increase in the activity of serum creatine kinase-MB, level of serum troponin-T and increased intensities of serum lactate dehydrogenase 1 and 2-isoenzymes. The rats also showed significant increased levels of heart lipid peroxidation products and significant decreased activities of heart superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and levels of reduced glutathione. Pretreatment with (-) epicatechin revealed significant protective effects on all the biochemical parameters and electrocardiogram investigated. Histopathology of myocardium confirmed the present findings. The in vitro study on the effects of (-) epicatechin on scavenging free radical 1,1-diphenyl-2-picrylhydrazyl revealed the free radical scavenging potential of (-) epicatechin. Thus, (-) epicatechin exerts protective effects against isoproterenol-induced oxidative stress thereby reducing cardiac tissue damage by its free radical scavenging and antioxidant effects.