Serum Creatine Kinase Activity Research Articles

Kir6.2-containing ATP-sensitive K+ channel is required for cardioprotection of resveratrol in mice

BackgroundResveratrol is a natural compound that affects energy metabolism and is also known to possess an array of cardioprotective effects. However, its overall effects on energy metabolism and the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothesize that ATP-sensitive potassium (K-ATP) channels as molecular sensors of cellular metabolism may mediate the cardioprotective effects of resveratrol.MethodsKir6.2 knockout, Kir6.1 heterozygous and wild-type (WT) mice were subjected to ischemia/reperfusion injury and were injected with resveratrol (10 mg/kg, i.p). Myocardial infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities were determined. Neonatal cardiomyocytes were used in in vitro assays to investigate the underlying mechanism of resveratrol in cardioprotection.ResultsResveratrol treatment significantly reduced myocardial infarct size and serum LDH and CK activity and inhibited oxygen-glucose deprivation/reoxygenation – induced cardiomyocyte apoptosis in WT and Kir6.1 heterozygous mice, but Kir6.2 deficiency can abolish the cardioprotective effects of resveratrol in vivo and in vitro. We further found that resveratrol enhanced 5′-AMP-activated protein kinase (AMPK) phosphorylation and promoted the association of AMPK with Kir6.2. Suppression of AMPK attenuated and activation of AMPK mimicked the cardioprotective effects of resveratrol in cardiomyocytes. Notably, Kir6.2 knockout also reversed the cardioprotection of AMPK activator.ConclusionsOur study demonstrates that resveratrol exerts cardioprotective effects through AMPK -Kir6.2/K-ATP signal pathway and Kir6.2-containing K-ATP channel is required for cardioprotection of resveratrol.

In Memoriam

In Memoriam

Evaluation of creatine kinase activity and inorganic phosphate concentration in adult nigerian homozygous and heterozygous hemoglobin phenotypes.

Background:Biochemical parameters vary in subjects with different hemoglobin phenotypes, compared with normal controls.Aim:The aim was to evaluate serum creatine kinase (CK) activity and inorganic phosphate concentrations in Nigerian adults with homozygous and heterozygous hemoglobin phenotypes.Subjects and Methods:A prospective study, carried out at the hematology out-patient clinic of our hospital, a community health center and a private hospital, all in Anambra state. Subjects included hemoglobin phenotypes AA, AS, and SS, in steady state and vaso-occlusive crisis (VOC). Samples were collected for serum CK activity and inorganic phosphate concentrations. Data obtained were analyzed using SPSS 16.0 (SPSS Inc., Chicago IL, USA). Means were compared using the Student's t-test and statistical significance was set at P < 0.05.Results:A total of 100 subjects participated in the study. There was a statistically significant difference in the means of serum CK activity in hemoglobin SS (HbSS) in VOC versus hemoglobin AA (HbAA) (P = 0.01) and HbSS in steady state versus HbAA (P = 0.02) but not in hemoglobin AS (HbAS) versus HbAA (P = 0.79) and HbSS in VOC versus HbSS in steady state (P = 0.06). A statistically significant difference was noted in the means of serum inorganic phosphate concentration in HbSS in VOC versus HbAA (P = 0.01), but not in HbSS in steady state versus HbAA (P = 0.43), HbSS in VOC versus HbSS in steady state (P = 0.09) and HbAS versus HbAA (P = 0.20).Conclusion:Sickle cell disease is a predictor for high serum CK activity and low serum concentration of inorganic phosphate, particularly in VOC. There may be a need to monitor serum CK activity in HbSS subjects presenting with major VOC.

Effects of ginsenosides-Rb1 on exercise-induced oxidative stress in forced swimming mice.

Background:The fleshy root of Panax ginseng C.A. Meyer (ginseng) is one of the most well-known and valued herbs in traditional Chinese medicine. Ginsenosides are considered mainly responsible for the pharmacological activities of ginseng. The purpose of this study was to investigate the effects of ginsenoside-Rb1 (G-Rb1) on swimming exercise-induced oxidative stress in male mice.Materials and Methods:A total of 48 animals were randomly divided into four groups, with twelve mice in each group. The first, second and third groups were designed as G-Rb1 treatment groups, got 25, 50 and 100 mg/kg bodyweight of G-Rb1, respectively. The fourth group was designed as the control group, got physiologic saline. The mice were intragastrically administered once daily for 4 weeks. The weight-loaded forced swimming test was conducted on the final day of experimentation. Then the exhaustive swimming time, blood lactate, serum creatine kinase (CK), malondialdehyde (MDA) and antioxidant enzymes in liver of mice were measured.Results:The results showed that G-Rb1 could prolong the exhaustive swimming time and improve exercise endurance capacity of mice, as well as accelerate the clearance of blood lactate and decrease serum CK activities. Meanwhile, G-Rb1 could decrease MDA contents and increase superoxide dismutase, catalase, glutathione peroxidase activities in liver of mice.Conclusions:The study suggested that G-Rb1 possessed protective effects on swimming exercise-induced oxidative stress in mice.

High-dose subcutaneous immunoglobulins for the treatment of severe treatment-resistant polymyositis.

Polymyositis is a rare debilitating condition characterized by chronic inflammation and muscle weakness. Standard treatments include corticosteroids and immunosuppressants; however, resistance to these regimens may develop. Intravenous immunoglobulins (IVIg) are thus recommended for patients with drug-resistant polymyositis. The patient presented a resistant polymyositis with severe muscle weakness, increasing dysphagia, and significant loss in weight. Subcutaneous immunoglobulins (SCIg) were initiated after failure of steroids and immunosuppressive drugs. SCIg was given twice per week (2 then 1.3 g/kg/month). Clinical recovery was observed within 2 months after the SCIg initiation. After several injections, the patient showed a progressive improvement in muscle strength. Serum creatine kinase activity decreased to normal levels, and dysphagia was resolved. The SC injections were generally well tolerated and good patient satisfaction was reported. This promising observation suggests that SCIg may be useful in active and refractory polymyositis.

Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population. NASH and to some extent NAFLD have been associated with increased liver-related and all-cause mortality. No effective treatment is yet available. Recent reports have shown that the use of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with elevated plasma aminotransferases may result in normalisation of these liver enzymes. Whether this is a consistent effect or whether it can lead to improved clinical outcomes beyond normalisation of abnormal liver enzymes is not clear. To assess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH. We performed a computerised literature search in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded up to March 2013. We did fully recursive searches from the reference lists of all retrieved relevant publications to ensure a complete and comprehensive search of the published literature. We did not apply any restrictions regarding language of publication or publication date. All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents. Data were extracted, and risk of bias of each trial was assessed independently by two or more review authors. Meta-analyses were performed whenever possible. Review Manager 5.2 was used. When the described search method was used and the eligibility criteria of the search results were applied, 653 records were found. Only two of these were randomised clinical trials that were considered eligible for inclusion. We assessed both trials as trials with high risk of bias. One of the trials was a pilot trial in which 16 participants with biopsy-proven NASH were randomised to receive simvastatin 40 mg (n = 10) or placebo (n = 6) once daily for 12 months. No statistically significant improvement in the aminotransferase level was seen in the simvastatin group compared with the placebo group. Liver histology was not significantly affected by simvastatin.The other trial had three arms. The trial compared atorvastatin 20 mg daily (n = 63) versus fenofibrate 200 mg daily (n = 62) versus a group treated with a combination of the two interventions (n = 61). There were no statistically significant differences between any of the three intervention groups regarding the week 54 mean activity levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed to be higher in the fenofibrate group compared with the atorvastatin group (58% versus 33%). Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity; one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to alanine aminotransferase activity that was over three times the upper normal limit.No data for all-cause mortality and hepatic-related mortality were reported in the included trials. Based on the findings of this review, which included two trials with high risk of bias and a small numbers of participants, it seems possible that statins may improve serum aminotransferase levels as well as ultrasound findings. Neither of the trials reported on possible histological changes, liver-related morbidity or mortality. Trials with larger sample sizes and low risk of bias are necessary before we may suggest statins as an effective treatment for patients with NASH. However, as statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified.

Dystrophin insufficiency causes selective muscle histopathology and loss of dystrophin‐glycoprotein complex assembly in pig skeletal muscle

The purpose of this investigation was to determine the extent to which dystrophin insufficiency caused histomorphological changes in a novel pig model of Becker muscular dystrophy. In our procedures, we used a combination of biochemical approaches, including quantitative PCR and Western blots, along with a histological analysis using standard and immunohistological measures. We found that 8-wk-old male affected pigs had a 70% reduction in dystrophin protein abundance in the diaphragm, psoas major, and longissimus lumborum and a 5-fold increase in serum creatine kinase activity compared with healthy male littermates. Dystrophin insufficiency in the diaphragm and the longissimus resulted in muscle histopathology with disorganized fibrosis that often colocalized with fatty infiltration but not the psoas. Affected animals also had an 80-85% reduction in α-sarcoglycan localization in these muscles, indicating compromised assembly of the dystrophin glycoprotein complex. Controls used in this study were 4 healthy male littermates, as they are most closely related to the affected animals. We concluded that pigs with insufficient dystrophin protein expression have a phenotype consistent with human dystrophinopathy patients. Given that and their similarity in body size and physiology to humans, we further conclude that this pig line is an appropriate translational model for dystrophinopathies.

Bone‐muscle unit activity, salivary steroid hormones profile, and physical effort over a 3‐week stage race

Muscle traction and bone metabolism are functionally linked and co-regulated by a series of factors. Although a role for steroid hormones was hypothesized, a clear definition of the bone-muscle interconnection still lacks. To investigate this relationship, we studied bone metabolism, muscle activity, and salivary steroid hormones profile in relation with the physical effort across a cycling stage race, a model of effort in absence of load. Nine pro-cyclists were recruited; body weight and power output/energy expenditure were recorded. Diet was kept constant. Saliva was collected at days -1, 4, 8, 12, 14, 19, and 23; blood and urine were collected at days -1, 12, and 23. Salivary steroid hormones [cortisol, dehydroepiandrosterone (DHEA), testosterone, and estradiol], serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and creatine kinase (CK) activities, plasma sclerostin, and urinary calcium and phosphorous were measured. Cortisol remained constant, testosterone decreased at day 4, and estradiol and DHEA firstly increased and then returned to basal levels. Hormone concentrations were not correlated with plasma volume shifts. LDH, CK, AST, sclerostin, and urinary calcium and phosphorous increased. DHEA and estradiol correlated with the physical effort and the bone-muscular markers. A relationship between muscle activity, in absence of load, and bone resorption emerged under a putative regulation by DHEA and estradiol.

Effects of ischemic preconditioning on myocardium Caspase-3, SOCS-1, SOCS-3, TNF-α and IL-6 mRNA expression levels in myocardium IR rats

The aim of this study was to characterise the effects of ischemic preconditioning (IP) on heart function parameters (ΔST and ΔT), activities of serum creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression levels and Apoptosis index in myocardium IR rats. Results showed that ΔST and ΔST values in IP group were markedly lower than those in IR group. Compared with IR group, IP significantly (p < 0.01) decreased serum CK (0.83 ± 0.09 vs 1.36 ± 0.15), LDH (5613 ± 462 vs 7106 ± 492) activities and MDA (11.32 ± 1.05 vs 15.49 ± 1.26) level, increased the serum NO (86.39 ± 7.03 vs 53.77 ± 4.27) level in IR group. The IP induced a significant decreased in myocardium Caspase-3 mRNA (0.303 ± 0.021 vs 0.515 ± 0.022) gene expression (p < 0.01) compared to IR model group. The IP induced a significant decreased in myocardium SOCS-1 (0.241 ± 0.031 vs 0.596 ± 0.036), SOCS-3 (0.258 ± 0.031 vs 0.713 ± 0.057), TNF-α (0.137 ± 0.011 vs 0.427 ± 0.035) and IL-6 (0.314 ± 0.021 vs 0.719 ± 0.064) mRNA gene expression (p < 0.01) compared to IR model group. We conclude that IP is effective in the therapy of heart disease. These findings may have implications for the clinical development of preconditioning-based therapies for ischemic heart disease.

Protective effect of ginseng against gamma-irradiation-induced oxidative stress and endothelial dysfunction in rats.

This study investigated the potential protective effects of ginseng on gamma-irradiation-induced oxidative stress and endothelial dysfunction in rats. Twenty four male albino rats were divided into four groups. In the control group, rats were administered vehicle by tube for 7 consecutive days. The second group was administered ginseng extract (100 mg/kg, by gavage) for 7 consecutive days. Animals in the third group were administered vehicle by tube for 7 consecutive days, then exposed to single dose gamma-irradiation (6 Gy). The Fourth group received ginseng extract for 7 consecutive days, one hour later rats were exposed to gamma-irradiation. Oral administration of ginseng extract prior to irradiation produced a significant protection which was evidenced by a significant reduction in serum creatine kinase (CPK) and lactate dehydrogenase (LDH) activities and asymmetric dimethylarginine (ADMA), urea and creatinine levels with significant increase in serum total nitrate/nitrite (NO(x)) level. Moreover, ginseng significantly increased cardiac and renal superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities, and reduced glutathione (GSH) content, associated with a significant depletion in malondialdehyde (MDA) and NO(x) levels compared to irradiated group. This study suggests that ginseng may serve as a potential protective agent against gamma-irradiation-induced cardio-nephrotoxicity via enhancing the antioxidant activity and inhibition of endothelial dysfunction.

P.11.2 Naproxcinod, a nitric oxide-donating anti-inflammatory compound, is effective in two mouse models of muscle dystrophy

Nitric oxide (NO) plays a critical role in skeletal muscle function, including control of blood flow and muscle repair. In muscular dystrophies, synthesis of NO in the skeletal muscle is known to be defective therefore contributing to damage progression. In the present study, we evaluated the effects of naproxcinod, an NO-donating anti-inflammatory compound, in two models of muscular dystrophy, the alpha-sarcoglycan (alpha-SG) null mice, a model for limb-girdle muscle dystrophy, and the mdx mouse model for Duchenne muscle dystrophy (DMD). Naproxcinod (10 and 30 mg/kg/day) was orally administered for 7 months to mdx mice and for 4 months to alpha-SG null mice starting at 4 weeks of age. Muscle function was assessed by treadmill test at 4 months (both mdx and alpha-SG null mice) and 7 months of treatment (mdx mice). Serum creatine kinase (CK) was measured as index of skeletal muscle damage. Inflammatory infiltrates, as well as muscle regeneration were studied in diaphragm and tibialis anterior muscles. In mdx mice 30 mg/kg/day of naproxcinod significantly improved muscle function in terms of resistance to exercise with a recovery score of 12%; significantly reduced skeletal muscle inflammation and serum CK activity; and increased muscle regeneration. Likewise in alpha-SG null mice, 4 months of naproxcinod treatment led to a significant improvement of resistance to fatigue (recovery score of 59%), and to reduction of muscle inflammation and damage. Furthermore, both diaphragm and tibialis anterior muscles appeared fully regenerated, thus supporting the marked beneficial effects observed for muscle function. The results demonstrate that naproxcinod, through NO donation together with anti-inflammatory activity, produces significant and persistent therapeutic effects improving muscle function, reducing muscle inflammation and maintaining regeneration capacity of the muscle in two models of muscular dystrophies.

P.14.10 Respiratory failure as presenting symptom of paraneoplastic necrotizing autoimmune myopathy

Necrotizing autoimmune myopathy (NAM) is associated with cancer, connective tissue disorders, and statin use. Respiratory failure as a presenting symptom has been reported in rare cases of other inflammatory myopathies, but not in NAM. A 48-year-old woman was acutely admitted with severe hypercapnia which required immediate endotracheal intubation. History revealed that she experienced shortness of breath since one month. Her past medical history included a mastectomy 2years prior to admission, because of noninvasive ductal mammacarcinoma. On admission there was mild symmetrical proximal weakness of her arms and legs and slightly more pronounced distal weakness of her legs, as well as weakness of her neck flexor muscles, which in retrospect had been gradually progressive in the weeks before presentation. Serum creatine kinase activity was five times the upper limit of normal and electromyography exhibited extensive myopathic changes. Magnetic resonance imaging (T2 weighted images) showed hyperintensity of the pelvic girdle and proximal leg muscles. Muscle biopsy showed extensive muscle fibre necrosis in the absence of inflammatory cells. Myositis immunoblot did not show myositis specific antibodies. A diagnosis of paraneoplastic NAM was made and monthly courses of oral dexamethasone pulse therapy was started which led to prompt extubation and remarkable recovery of muscle strength in weeks. Acute respiratory failure can be a presenting symptom in paraneoplastic necrotizing autoimmune myopathy. Paraneoplastic NAM should be considered in all patients with (sub) acute onset of symmetrical and progressive limb weakness and a history of malignancy. Immunosuppressive therapy can lead to substantial recovery.

Beneficial effects of a polysaccharide from Salvia miltiorrhiza on myocardial ischemia–reperfusion injury in rats

In the present study, one water-soluble polysaccharide (SMP1) was isolated from the roots of Salvia miltiorrhiza. The cardio-protective potential of SMP1 was studied in the ischemia–reperfusion (I/R) model of rats in vivo. Results showed that 30min of left anterior descending coronary artery occlusion (LAD) followed by 4h of reperfusion markedly decreased myocardial superoxide dismutase (SOD), Na+–K+-ATPase and Ca2+–Mg2+-ATPase activities and increased myocardial malondialdehyde (MDA) level and serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in I/R rats. An increase in infarct size and high apoptosis index of cardiac cell were also observed in IR rats. Administration of SMP1 400 and 800mg/kg significantly reversed these biochemical parameters in the I/R rats to the normal levels in sham control rats. The infarct sizes and the percent of TUNEL-positive cells were found significantly decreased in SMP1-treated groups compared to I/R rats. Taken together, the present study clearly suggests SMP1 has a protective effect against myocardial I/R injury in rats by ameliorating oxidative stress and inhibiting myocardial apoptosis.

A contralateral repeated bout effect attenuates induction of NF-κB DNA binding following eccentric exercise

We investigated the existence of contralateral repeated bout effect and tested if the attenuation of nuclear factor-kappa B (NF-κB; an important regulator of muscle inflammation) induction following eccentric exercise is a potential mechanism. Thirty-one healthy men performed two bouts of knee extension eccentric exercise, initially with one leg and then with the opposite leg 4 wk later. Vastus lateralis muscle biopsies of both exercised and control legs were taken 3 h postexercise. Knee extension isometric and isokinetic strength (60°/sec and 180°/sec) were measured at baseline, pre-exercise, immediately postexercise, and 1/day for 5 days postexercise. Serum creatine kinase (CK) activity and muscle soreness were assessed at baseline and 1/day for 5 days postexercise. NF-κB (p65) DNA-binding activity was measured in the muscle biopsies. Isometric strength loss was lower in bout 2 than in bout 1 at 24, 72, and 96 h postexercise (P < 0.05). Isokinetic strength (60°/s and 180°/s) was reduced less in bout 2 than in bout 1 at 72 h postexercise (P < 0.01). There were no significant differences between bouts for postexercise CK activity or muscle soreness. p65 DNA-binding activity was increased following eccentric exercise (compared with the control leg) in bout 1 (122.9% ± 2.6%; P < 0.001) and bout 2 (109.1% ± 3.0%; P < 0.05). Compared with bout 1, the increase in NF-κB DNA-binding activity postexercise was attenuated after bout 2 (P = 0.0008). Repeated eccentric exercise results in a contralateral repeated bout effect, which could be due to the attenuated increase in NF-κB activity postexercise.

Estrogens protect myocardium against ischemia/reperfusion insult by up-regulation of CRH receptor type 2 in female rats

BackgroundThe mechanism underlying estrogen cardioprotection remains largely unknown. Urocortin (UCN), a member of corticotropin-releasing hormone (CRH) family, is one of endogenous cardioprotective factors. The goal of present study is to investigate whether estrogens regulate UCN and its receptor CRH receptor type 2 (CRHR2) in female rat heart. Methods17β-estradiol (E2) was subcutaneously administrated to ovariectomized (OVX) rats for eight weeks. UCN was administrated before simulated myocardial ischemia/reperfusion (I/R). Cell damage was assessed by measurement of infarct size, activity of serum creatine kinase (CK) and lactate dehydrogenase (LDH) and percentage of TUNEL staining in myocardium. The mRNA and protein levels of UCN and CRHR2 were determined in sham operated and OVX rats with or without E2 replacement. DNA methylation frequency of CRHR2 gene promoter was determined by bisulfite-sequencing. ResultsUCN administration reduced infarct size, LDH and CK level and percentage of TUNEL staining upon I/R injury. The cardioprotective effects of UCN were abrogated in OVX rats and E2 replacement restored UCN-induced cardioprotection.CRHR2 mRNA and protein expression were down-regulated more than 40% in OVX rats, both of which were restored by E2 replacement. UCN mRNA and protein levels were not affected by ovariectomy and E2 replacement. Hypermethylation in CRHR2 promoter was found in OVX rats, and two of the methylated CpG sites were seated at cis-acting elements. Hypermethylation induced by OVX could also be ameliorated by E2 replacement. ConclusionEstrogens maintain CRHR2 expression in myocardium, which may through an epigenetic mechanism, and enhance UCN-induced cardioprotective effects against I/R injury.

Role of stress in myocardial protection of ischemic preconditioning

To determine the role of stress in myocardial protection of ischemic preconditioning (IPC). Thirty rabbits were randomly divided into an IPC group, an etomidate (Etom) group, an ischemic/reperfusion (IR) group, a methylprednisolone (MP) group and a sham group. The ratio of infarction size versus risk area (infarct/risk) was calculated. The elevations of the serum creatine kinase (CK) activity and cardiac troponin I (cTnI) concentrations as well as the serum cortisol concentrations were measured. The percentages of infarct/risk in the IPC group, the MP group, the IR group, and the Etom group were (5.86±2.81)%, (11.28±3.62)%, (26.79±4.53)%, and (18.19±3.72)%, respectively. The elevations of the serum CK activity in the IPC group, the MP group, the IR group, and the Etom group were (255±89), (314±160), (855±371), and (768±404) U/L, respectively. The elevations of serum cTnI concentrations in the IPC group, the MP group, the IR group, and the Etom group were (3.6±0.6),(6.1±2.2), (8.1±3.6), and (6.4±1.6) μg/L, respectively. Those indicators among the groups were significantly different (P<0.05). Cortisol reaction was markedly diminished in the Etom group. A blunted cortisol reaction can markedly reduce the benefit of IPC while methylprednisolone shows cardioprotective effects, suggesting that stress might be involved in the myocardial protection of IPC.

Effect of edaravone on myocardial injury in patients undergoing off-pump coronary artery bypass grafting

Objective To evaluate the effect of edaravone on myocardial injury in patients undergoing offpump coronary artery bypass grafting (OPCABG).Methods Forty ASA physical status Ⅲ-Ⅳ patients,aged 45-64 yr,weighing 55-95 kg,with NYHA class Ⅱ-Ⅲ,scheduled for elective OPCABG,were randomly divided into 2 groups (n =20):edaravone group (group E) and control group (group C).After induction of anesthesia,edaravone 60 mg (in 100 ml of normal saline) was infused over 30 min in group E,while the equal volume of normal saline was given instead of edaravone in group C.Venous blood samples were taken before operation (T1),after skin incision (T2),at the end of operation (T3),and at 24 h after operation (T4) to measure the serum levels of myocardial enzymes and cardiac troponin Ⅰ (cTnI).The time for ventilator treatment,duration of stay in the intensive care unit and duration of stay in hospital were recorded.Results Compared with group C,the activities of serum creatine kinase,creatine kinase isoenzyme-MB,aspartate aminotransferase and lactate dehydrogenase and cTnI concentrations were significantly increased at T3 and T4 (P ＜ 0.05) and no significant changes were found at T1 in group E (P ＞ 0.05).The parameters mentioned above were significantly higher at T3 and T4 than at T1 in the two groups (P ＜ 0.05).The time for ventilator treatment,duration of stay in the intensive care unit and duration of stay in hospital were significantly shortened in group E as compared with group C (P ＜ 0.05 or 0.01).Conclusion Edaravone 60 mg infused before OPCABG can provide effective myocardial protection in patients. Key words: Free radical scavengers; Reactive oxygen species; Coronary artery bypass, off-pump; Myocardial reperfusion injury

Protective effect of Yixinshu capsule on myocardial ischemia reperfusion injury in rats

To observe the protective effect of Yixinshu capsule on myocardial ischemia reperfusion injury (MIRI) in SD rats. Sixty healthy SD rats were randomized into six groups: sham group, MIRI model group, Xinsuning capsule group, low, middle or high dose Yixinshu capsule. Acute MIRI rat models were created by reperfusion for 120 min after anterior interventricular branch of the left coronary artery for 30 min. The serum creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and malondialdehyde(MDA), blood viscosity, and infarction area of myocardium were determined. Yixinshu capsule could reduce serum CK, LDH, AST and LDH activity, improve the blood viscosity, and reduced the myocardial infarct size. Yixinshu capsule can protect against MIRI in rats.

Serum activity of creatine kinase and aminotransferase aspartate enzymes of horses submitted to muscle biopsy and incremental jump test

The objective was to evaluate serum activity of the enzymes creatine kinase (CK) and aspartate aminotransferase (AST), which are leakage enzymes responsive to muscle injury, of athletic horses that underwent muscle biopsy and incremental jump test (IJT) involving incremental jumps. The animals were grouped as follows: the first group, horses with history of superior performance (SP); the second, with a history of inferior performance (IP); and lastly, a control group (CG). All groups underwent biopsy of the gluteus medius muscle, while groups SP and IP were also submitted to the incremental jump test (IJT) 24 hours after biopsy. The IJT consisted of three stages with 40 jumps each, where jump height increased progressively, from 40 to 60 and last, 80cm. Blood samples were drawn before biopsy, and 6 and 24 hours after the exercise as well. The levels of CK serum activity increased 6 hours after exercise and decreased 24 hours later in all groups, including CG. AST activity did not increase after biopsy and exercise. There was no increase of both enzyme activities that could be attributed to the exercise, possibly due to exercise short duration and/or low intensity. We conclude that the muscle biopsy was able to show that there was enough stimulus to cause CK enzyme leakage into the plasma, and consequent detection of increased serum activity, while the incremental jump test did not.

Role of Kir6.2 subunits of ATP-sensitive potassium channels in endotoxemia-induced cardiac dysfunction

BackgroundCardiac dysfunction is well-described in endotoxemia and diagnosed in up to 60% of patients with endotoxic shock. ATP-sensitive potassium (KATP) channels are critical to cardiac function. This study investigates the role of Kir6.2 subunits of KATP channels on cardiac dysfunction in lipopolysaccharide (LPS)-induced endotoxemia.MethodsKir6.2 subunits knockout (Kir6.2−/−) and wild-type (WT) mice were injected with LPS to induce endotoxemia. Cardiac function was monitored by echocardiography. Left ventricles were taken for microscopy (both light and electron) and TUNEL examination. Serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, and tumor necrosis factor-α (TNF-α) levels in both serum and left ventricular tissues were determined.ResultsCompared to WT, Kir6.2−/− mice showed significantly declined cardiac function 360 min after LPS administration, aggravated myocardial damage and elevated serum LDH and CK activities. Apoptotic cells were obviously increased in heart tissues from Kir6.2−/− mice at 90, 180 and 360 min. TNF-α expression in both serum and heart tissues of Kir6.2−/− mice was significantly increased.ConclusionsWe conclude that Kir6.2 subunits are critical in resistance to endotoxemia-induced cardiac dysfunction through reducing myocardial damage by inhibition of apoptosis and inflammation. KATP channels blockers are extensively used in the treatment of diabetes, their potential role should therefore be considered in the clinic when patients treated with antidiabetic sulfonylureas are complicated by endotoxemia.