Impact of low-flow ischemia on substrate oxidation and glycolysis in the isolated perfused rat heart

2004 ◽  
Vol 287 (1) ◽  
pp. H351-H362 ◽  
Author(s):  
Steven G. Lloyd ◽  
Peipei Wang ◽  
Huadong Zeng ◽  
John C. Chatham
Keyword(s):  
Myocardial Ischemia ◽  
Protective Effect ◽  
Citrate Synthase ◽  
Substrate Oxidation ◽  
Low Flow ◽  
Control Group ◽  
Lactate Oxidation ◽  
Carbohydrate Utilization ◽  
Atp Production ◽  
Oxidative Energy Metabolism

Interventions that stimulate carbohydrate oxidation appear to be beneficial in the setting of myocardial ischemia or infarction. However, the mechanisms underlying this protective effect have not been defined, in part because of our limited understanding of substrate utilization under ischemic conditions. Therefore, we used 1H and 13C NMR spectroscopy to investigate substrate oxidation and glycolytic rates in a global low-flow model of myocardial ischemia. Isolated male Sprague-Dawley rat hearts were perfused for 30 min under conditions of normal flow (control) and low-flow ischemia (LFI, 0.3 ml/min) with insulin and 13C-labeled lactate, pyruvate, palmitate, and glucose at concentrations representative of the physiological fed state. Despite a ∼50-fold reduction in substrate delivery and oxygen consumption, oxidation of all exogenous substrates plus glycogen occurred during LFI. Oxidative metabolism accounted for 97% of total calculated ATP production in the control group and ∼30% in the LFI group. For controls, lactate oxidation was the major source of ATP; however, in LFI, this shifted to a combination of oxidative and nonoxidative glycogen metabolism. Interestingly, in the LFI group, anaplerosis relative to citrate synthase increased sevenfold compared with controls. These results demonstrate the importance of oxidative energy metabolism for ATP production, even during very-low-flow ischemia. We believe that the approach described here will be valuable for future investigations into the underlying mechanisms related to the protective effect of increasing cardiac carbohydrate utilization and may ultimately lead to identification of new therapeutic targets for treatment of myocardial ischemia.

scholarly journals Protective Effects of Chinese Traditional Medicine Buyang Huanwu Decoction on Myocardial Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Guangde Yang ◽  
Zhiyuan Fang ◽  
Yu Liu ◽  
Hui Zhang ◽  
Xiaolian Shi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Ischemia ◽  
Protective Effect ◽  
Myocardial Injury ◽  
Control Group ◽  
Protective Effects ◽  
Buyang Huanwu Decoction ◽  
Pre Treatment ◽  
Cluster Of Differentiation ◽  
Electrocardiogram Ecg

Many clinical studies have reported that Buyang Huanwu Decoction (BYHWD) has a protective effect on ischemic heart disease (IHD). In the present study, the protective effect of BYHWD on myocardial ischemia was investigated. Different doses of BYHWD and Compound Danshen Dropping Pills (CDDP) were lavaged to rats, respectively, isoproterenol (ISO) was intraperitoneally injected in to all animals to induce myocardial ischemia except the control group. Electrocardiogram (ECG) of each animal was recorded; activities of lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) in serum were detected. As the results of ECG showed, pre-treatment with BYHWD inhibited ischemic myocardial injury, and the activities of LDH, CK and AST were lower than those in the myocardial ischemia model group, which suggests that BYHWD rescues the myocardium from ischemia status. To research the potential mechanism, the level of nitric oxide (NO), nitric oxide syntheses (NOS) and inducible nitric oxide syntheses (iNOS), the expression of iNOS and ligand of cluster of differentiation 40 (CD40L) were detected. The results revealed that BYHWD significantly decreased the level of NO, NOS and iNOS in serum. Moreover, BYHWD decreased the expression of iNOS and CD40L in myocardial tissues. These results indicate that the protective effect of BYHWD on myocardial ischemia and mechanism are associated with inhibition of iNOS and CD40L expression.

scholarly journals Study on the Protective Effect of Edaravone on Myocardial Ischemia Reperfusion Injury

2013 ◽  
Vol 2 ◽  
pp. 10
Author(s):  
Hui Hou
Keyword(s):  
Treatment Group ◽  
Myocardial Ischemia ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Acute Myocardial Ischemia ◽  
Control Group ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

<div><p><strong>Objective: </strong>Discussion the role of edaravone as a free radical scavenger in protective effect of thrombolysis in acute myocardial ischemia reperfusion injury. Besides compared with the control group and analyze the possible mechanism which is widely used in clinical setting. <strong>Method: </strong>80 patients hospitalized within year 2012−2013 with acute myocardial infarction (AMI) were treated with intravenous thrombolytic therapy, and were divided into treatment group (n = 41) and control group (n = 39). Edaravone injection 30 mg + 0.9% normal saline solution 100 mL with intravenous drip, BID for 14 days was given to the treatment group before and after thrombolytic treatment. Whereas, control group was treated with intravenous drip of placebo. Both groups were monitored by echocardiography and hemodynamic monitoring, and the myocardium was measured by echocardiography. Coronary artery CT was used to determine the degree of obstruction. <strong>Results: </strong>Compared with the control group, pain and reperfusion arrhythmia in treatment group was reduced. The area of myocardial wall movement disorder was significantly decreased (<em>p</em> &lt; 0.05), the difference was statistically significant. CT result comparing treatment group and control group and show that rate of coronary recanalization increases 1.7 times (<em>p </em>&lt; 0.01), the differences were statistically significant. <strong>Conclusion: </strong>For acute myocardial ischemia injection of edaravone before reperfusion and combine with pharmacological treatment can alleviate myocardial ischemia reperfusion injury, effectively scavenge oxygen free radicals and improve the ability of antioxidant. Both improve the thrombolytic treatment and protective effect for acute myocardial ischemia were significant. Hence, edaravone can is a kind of new milestone in the clinical cardiovascular drugs.</p></div>

Influence of Ca2+ on mitochondrial apoptosis activation and yak meat tenderization during postmortem aging

2021 ◽  
pp. 1-12
Author(s):  
Lin-lin Wang ◽  
Lian-hong Chen ◽  
Jian Li ◽  
Rong-sheng Du ◽  
Ling Han ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Citrate Synthase ◽  
Control Group ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Atp Production ◽  
Mitochondrial Apoptosis Pathway ◽  
Mitochondrial Functions ◽  
Postmortem Aging ◽  
Meat Tenderization

The objective of this study was to investigate the underlying molecular mechanisms of mitochondrial Ca2+ homeostasis disequilibrium in mitochondrial apoptosis and its impact on yak meat tenderness. Results indicated that CaCl2 treatment significantly promoted glycolysis by increasing lactic acid level and decreasing glycogen content, pH, and ATP production (P < 0.01 and P < 0.05). The activities of Na+-K+-ATPase pump and Ca2+-ATPase pump in the early aging stage were significantly influenced by CaCl2 treatment. The activities of synchronous digital hierarchy and citrate synthase were also significantly improved by CaCl2 treatment (P < 0.01 and P < 0.05). Mitochondrial reactive oxygen species (ROS) levels were significantly higher in the CaCl2 group than in the control group (P < 0.01); at 24 h, the value in the Ca2+ group was 64.27% higher than that in the control group. Furthermore, CaCl2 treatment significantly enhanced the mitochondrial apoptosis cascade reaction and meat tenderization by improving the myofibril fragmentation index and shear force (P < 0.01). These results demonstrated that the imbalance of mitochondrial Ca2+ homeostasis played a significant role in the mitochondrial apoptosis pathway by regulating energy metabolism factors, meat intracellular environment, mitochondrial functions, and ROS-mediated oxidative stress. These conditions further improved meat tenderization during postmortem aging.

Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats

2005 ◽  
Vol 288 (5) ◽  
pp. H2102-H2110 ◽  
Author(s):  
Peipei Wang ◽  
Steven G. Lloyd ◽  
Huadong Zeng ◽  
Arend Bonen ◽  
John C. Chatham
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Cardiac Function ◽  
Energy Production ◽  
Cardiac Metabolism ◽  
Low Flow ◽  
Control Group ◽  
Atp Production ◽  
Oxidation Rates ◽  
Zucker Diabetic Fatty Rats

The goal of this study was to determine whether changes in cardiac metabolism in Type 2 diabetes are associated with contractile dysfunction or impaired response to ischemia. Hearts from Zucker diabetic fatty (ZDF) and lean control rats were isolated and perfused with glucose, lactate, pyruvate, and palmitate. The rates of glucose, lactate, pyruvate, and palmitate oxidation rates and glycolysis were determined during baseline perfusion and low-flow ischemia (LFI; 0.3 ml/min for 30 min) and after LFI and reperfusion. Under all conditions, ATP synthesis from palmitate was increased and synthesis from lactate was decreased in the ZDF group, whereas the contribution from glucose was unchanged. During baseline perfusion, the rate of glycolysis was lower in the ZDF group; however, during LFI and reperfusion, there were no differences between groups. Despite these metabolic shifts, there were no differences in oxygen consumption or ATP production rates between the groups under any perfusion conditions. Cardiac function was slightly depressed before LFI in the ZDF group, but during reperfusion, function was improved relative to the control group despite the increased dependence on fatty acids for energy production. These data suggest that in this model of diabetes, the shift from carbohydrates to fatty acids for oxidative energy production did not increase myocardial oxygen consumption and was not associated with impaired response to ischemia and reperfusion.

Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Protective Effect ◽  
Cell Damage ◽  
Memory Loss ◽  
Control Group ◽  
Total Extract ◽  
Swiss Mice ◽  
Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans

2005 ◽  
Vol 98 (6) ◽  
pp. 1985-1990 ◽  
Author(s):  
Kirsten A. Burgomaster ◽  
Scott C. Hughes ◽  
George J. F. Heigenhauser ◽  
Suzanne N. Bradwell ◽  
Martin J. Gibala
Keyword(s):  
Citrate Synthase ◽  
Training Session ◽  
Interval Training ◽  
Maximal Activity ◽  
Work Capacity ◽  
Control Group ◽  
Endurance Capacity ◽  
Sprint Interval Training ◽  
Oxidative Potential ◽  
Cycle Endurance

Parra et al. ( Acta Physiol. Scand 169: 157–165, 2000) showed that 2 wk of daily sprint interval training (SIT) increased citrate synthase (CS) maximal activity but did not change “anaerobic” work capacity, possibly because of chronic fatigue induced by daily training. The effect of fewer SIT sessions on muscle oxidative potential is unknown, and aside from changes in peak oxygen uptake (V̇o2 peak), no study has examined the effect of SIT on “aerobic” exercise capacity. We tested the hypothesis that six sessions of SIT, performed over 2 wk with 1–2 days rest between sessions to promote recovery, would increase CS maximal activity and endurance capacity during cycling at ∼80% V̇o2 peak. Eight recreationally active subjects [age = 22 ± 1 yr; V̇o2 peak = 45 ± 3 ml·kg−1·min−1 (mean ± SE)] were studied before and 3 days after SIT. Each training session consisted of four to seven “all-out” 30-s Wingate tests with 4 min of recovery. After SIT, CS maximal activity increased by 38% (5.5 ± 1.0 vs. 4.0 ± 0.7 mmol·kg protein−1·h−1) and resting muscle glycogen content increased by 26% (614 ± 39 vs. 489 ± 57 mmol/kg dry wt) (both P < 0.05). Most strikingly, cycle endurance capacity increased by 100% after SIT (51 ± 11 vs. 26 ± 5 min; P < 0.05), despite no change in V̇o2 peak. The coefficient of variation for the cycle test was 12.0%, and a control group ( n = 8) showed no change in performance when tested ∼2 wk apart without SIT. We conclude that short sprint interval training (∼15 min of intense exercise over 2 wk) increased muscle oxidative potential and doubled endurance capacity during intense aerobic cycling in recreationally active individuals.

scholarly journals Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liselotte Bruun Christiansen ◽  
Tine Lovsø Dohlmann ◽  
Trine Pagh Ludvigsen ◽  
Ewa Parfieniuk ◽  
Michal Ciborowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Obese Group ◽  
Control Group ◽  
Dependent Manner ◽  
Respiratory Capacity ◽  
Protein Carbonyl Content ◽  
Functional Changes ◽  
Mitochondrial Respiratory

AbstractStatins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.

scholarly journals Critical requirement of SOS1 RAS-GEF function for mitochondrial dynamics, metabolism, and redox homeostasis

Oncogene ◽  
2021 ◽  
Author(s):  
Rósula García-Navas ◽  
Pilar Liceras-Boillos ◽  
Carmela Gómez ◽  
Fernando C. Baltanás ◽  
Nuria Calzada ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Redox Homeostasis ◽  
Atp Production ◽  
Oxidative Energy Metabolism ◽  
Ras Activation ◽  
Mitochondrial Defects ◽  
Critical Requirement ◽  
Dynamics And Function ◽  
And Function ◽  
And Control

AbstractSOS1 ablation causes specific defective phenotypes in MEFs including increased levels of intracellular ROS. We showed that the mitochondria-targeted antioxidant MitoTEMPO restores normal endogenous ROS levels, suggesting predominant involvement of mitochondria in generation of this defective SOS1-dependent phenotype. The absence of SOS1 caused specific alterations of mitochondrial shape, mass, and dynamics accompanied by higher percentage of dysfunctional mitochondria and lower rates of electron transport in comparison to WT or SOS2-KO counterparts. SOS1-deficient MEFs also exhibited specific alterations of respiratory complexes and their assembly into mitochondrial supercomplexes and consistently reduced rates of respiration, glycolysis, and ATP production, together with distinctive patterns of substrate preference for oxidative energy metabolism and dependence on glucose for survival. RASless cells showed defective respiratory/metabolic phenotypes reminiscent of those of SOS1-deficient MEFs, suggesting that the mitochondrial defects of these cells are mechanistically linked to the absence of SOS1-GEF activity on cellular RAS targets. Our observations provide a direct mechanistic link between SOS1 and control of cellular oxidative stress and suggest that SOS1-mediated RAS activation is required for correct mitochondrial dynamics and function.

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