glycogen and Ventricular-Dysfunction--Left

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Dual-Specificity Phosphatases; Echocardiography; Glycogen; Humans; Lafora Disease; Mice; Mice, Knockout; Mutation; Myocytes, Cardiac; Protein Tyrosine Phosphatases, Non-Receptor; Seizures; Stroke Volume; Ubiquitin-Protein Ligases; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Adenosine Triphosphate; Animals; Coronary Circulation; Dietary Supplements; Disease Models, Animal; Energy Metabolism; Fatty Acids, Omega-3; Gene Expression Regulation; Glycogen; Inflammation Mediators; Lactic Acid; Male; Myocardial Infarction; Myocardium; Rats, Wistar; Signal Transduction; Soybean Oil; Systole; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

The effects of ischemic-postconditioning (IPOC) on functional recovery and cell viability of ischemic-reperfused hearts from fed and fasted rats were studied in relation to triacylglycerol and glycogen mobilization, ATP content, glucose-6-phosphate dehydrogenase activity and reduced/oxidized glutathione (GSH/GSSG). Oxidative damage was estimated by measuring thiobarbituric acid reactive substances (TBARS). IPOC improved contractile recovery and cell viability in the fed but attenuated them in the fasted hearts. In both groups ischemia lowered glycogen. IPOC further reduced it. Triacylglycerol remained unchanged during ischemia-reperfusion in both groups, but triacylglycerol mobilization was activated by IPOC in the fasted group. ATP was increased by IPOC in the fed hearts, but lowered in the fasted ones, which appeared to be associated with the rates of ATP synthesis in isolated mitochondria. In the fed hearts IPOC raised glucose-6-phosphate dehydrogenase activity and GSH/GSSG, and lowered TBARS. These results suggest that IPOC effects are associated with changes in the ATP supply, mobilization of energy sources and glutathione antioxidant ratio.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Cell Survival; Energy Metabolism; Fasting; Female; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Disulfide; Glycine; Glycogen; Heart; Heart Rate; Ischemic Postconditioning; Mitochondria, Heart; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Triglycerides; Ventricular Dysfunction, Left

Ventricular dysfunction is reported greater in the left (LV) versus right ventricle (RV) in infants following surgically induced ischemia. Ventricle-specific differences in baseline metabolism may alter response to ischemia thus affecting postischemic functional recovery. This study identifies ventricle-specific metabolic differences in the newborn (piglet) heart at baseline (working) and during ischemia (arrested). Baseline LV citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HAD) activities were 15% and 18% lower (p < 0.02), whereas creatine kinase (CK) and phosphofructokinase (PFK) activities were 40% and 23% higher (p < 0.04) than the RV. Baseline LV glycogen reserves were also 55% higher (p = 0.004). By 15 min of ischemia, LV ATP was 20% lower (p < 0.05), lactate was 51% higher (p = 0.001), and hydrogen ions (H) were 43% higher (p = 0.03) compared with the RV. These differences persisted for the entire ischemic period (p < 0.02). After 45 min of ischemia, the LV used 58% less (p < 0.05) glycogen than the RV. These findings demonstrate that the enhanced glycolytic capacity of the newborn LV was accompanied by greater anaerobic end-product accumulation and lower energy levels during ischemia. This profile may offer one explanation for greater LV-dysfunction relative to the RV in children following ischemia.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Adaptation, Physiological; Adenosine Triphosphate; Animals; Animals, Newborn; Citrate (si)-Synthase; Creatine Kinase; Energy Metabolism; Glycogen; Glycolysis; Heart Arrest, Induced; Heart Ventricles; Hydrogen-Ion Concentration; Lactic Acid; Myocardial Ischemia; Myocardium; Phosphofructokinases; Swine; Time Factors; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Many patients with heart failure have whole-body insulin resistance and reduced cardiac fluorodeoxyglucose uptake, but whether these metabolic changes have detrimental effects on the heart is unknown. Here, we tested whether there is a link between insulin resistance and ischemic damage in the chronically infarcted Wistar rat heart, postulating that the heart would have decreased insulin sensitivity, with lower GLUT4 glucose transporter protein levels due to high circulating free fatty acid (FFA) concentrations. A decreased capacity for glucose uptake would lower glycolytic adenosine triphosphate (ATP) production and thereby increase ischemic injury in the infarcted heart.. In vivo left ventricular ejection fractions, measured using echocardiography, were 40% lower in rats 10 weeks after coronary artery ligation than in sham-operated control rats. Insulin-stimulated D[2-3H]glucose uptake was 42% lower in isolated, perfused, infarcted hearts. Myocardial GLUT4 glucose transporter protein levels were 28% lower in the infarcted hearts and correlated negatively with ejection fractions and with fasting plasma FFA concentrations. Compared with controls, chronically infarcted hearts had 46% lower total glucose uptake and three-fold faster ATP hydrolysis rates, measured using phosphorus-31 nuclear magnetic resonance spectroscopy, during 32-min ischemia at 0.4 ml/min/gww. During reperfusion, recovery of left ventricular developed pressure in infarcted hearts was 42% lower than in control hearts.. Glucose uptake, in response to insulin or ischemia, was lower in the chronically infarcted rat heart and associated with increased circulating FFA concentrations and decreased GLUT4 levels. Thus, infarcted hearts had greater ATP depletion, and consequently incurred greater damage, during ischemia.

Topics: Adenosine Triphosphate; Animals; Echocardiography; Energy Metabolism; Fatty Acids, Nonesterified; Glucose; Glucose Transporter Type 4; Glycogen; Insulin; Insulin Resistance; Magnetic Resonance Spectroscopy; Male; Models, Animal; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Perfusion; Rats; Rats, Wistar; Time Factors; Ventricular Dysfunction, Left

Incessant tachycardia induces dilated cardiomyopathy in humans and experimental models; mechanisms are incompletely understood. We hypothesized that excessive chronotropic demands require compensatory contractility reductions to balance metabolic requirements. We studied 24 conscious dogs during rapid right ventricular (RV) pacing over 4 wk. We measured hemodynamic, coronary blood flow (CBF), myocardial O(2) consumption (MVO(2)) responses, myocardial nitric oxide (NO) production, and substrate utilization. Early pacing (6 h) resulted in decreased heart rate (HR)-adjusted coronary blood flow (CBF), MVO(2) (CBF/beat: 0.33 +/- 0.02 to 0.19 +/- 0.01 ml, P < 0.001, MVO(2)/beat: 0.031 +/- 0.002 to 0.016 +/- 0.001 ml O(2), P < 0.001), and contractility [left ventricular (LV) first derivative pressure (dP/dt)/LV end-diastolic diameter (EDD): 65 +/- 4 to 44 +/- 3 mmHg x s(-1) x mm(-1), P < 0.01], consistent with flow-metabolism-function coupling, which persisted over the first 72 h of pacing (CBF/beat: 0.15 +/- 0.01 ml, MVO(2)/beat: 0.013 +/- 0.001 ml O(2), P < 0.001). Thereafter, CBF per beat and MVO(2) per beat increased (CBF/beat: 0.25 +/- 0.01 ml, MVO(2)/beat: 0.021 +/- 0.001 ml O(2) at 28 days, P < 0.01 vs. 72 h). Contractility declined [(LV dP/dt)/LVEDD: 19 +/- 2 mmHg x s(-1) x mm(-1), P < 0.0001], signifying flow-function mismatch. Cardiac NO production, endothelial NO synthase expression, and fatty acid utilization decreased in late phase, whereas glycogen content and lactate uptake increased. Incessant tachycardia induces contractile, metabolic, and flow abnormalities reflecting flow-function matching early, but progresses to LV dysfunction late, despite restoration of flow and metabolism. The shift to flow-function mismatch is associated with impaired myocardial NO production.

Topics: Animals; Cell Respiration; Consciousness; Coronary Circulation; Dogs; Enzyme Inhibitors; Female; Glycogen; Lactic Acid; Male; Myocardial Contraction; Myocardial Stunning; Myocardium; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroarginine; Pacemaker, Artificial; Tachycardia; Ventricular Dysfunction, Left

We examined whether pharmacological inhibition of glycogenolysis by N-methyl-1-deoxynojirimycin (MOR-14), a new compound which reduces the glycogenolytic rate by inhibiting the alpha-1,6-glucosidase activity of the glycogen-debranching enzyme, can protect the heart against postischemic left ventricular dysfunction. The hearts of male Sprague-Dawley rats were excised, and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. The hearts were paced at 320 beats/min except during the ischemia. Left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s), and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min including a 30-min preischemic period followed by a 30-min episode of global ischemia and 60 min reperfusion. with or without 0.5 or 2 mM of MOR-14 during the 30-min preischemic period or the first 30 min of reperfusion. In another series of experiments, the myocardial content of glycogen and lactate was measured during the 30-min episode of ischemia in groups treated with and without 2mM of MOR-14. Preischemic but not postischemic treatment with MOR-14 significantly improved LVDP and +/-dP/dt without altering coronary flow during reperfusion in a dose-dependent manner. MOR-14 significantly preserved the glycogen content and significantly attenuated the lactate accumulation during the 30-min episode of ischemia. Preischemic treatment with MOR-14 is protective against postischemic left ventricular dysfunction through the inhibition of glycogenolysis in the isolated rat heart.

Topics: 1-Deoxynojirimycin; Adenosine Triphosphate; Animals; Blood Flow Velocity; Disease Models, Animal; Enzyme Inhibitors; Glycogen; Glycoside Hydrolase Inhibitors; Heart; Lactic Acid; Male; Myocardial Ischemia; Myocardial Reperfusion; Rats; Rats, Sprague-Dawley; Time Factors; Ventricular Dysfunction, Left

The objective of this study was to determine whether hypoxic preconditioning (HP) could lessen the myocardial increase in [Na+]i, thus protecting the aging myocardium against ischemia.. A decrease in ischemic tolerance with aging is associated with an accelerated increase in [Na+]i during ischemia. Ischemic preconditioning fails to protect the middle-aged and senescent myocardium against ischemia.. Isolated hearts of young adult (12-week-old), middle-aged (50-week-old) and senescent (100-week-old) Fischer 344 rats were subjected to 25 min of ischemia with or without HP followed by 30 min of reperfusion. Left ventricular (LV) function, myocardial energy metabolites and [Na+]i were measured.. In the older groups, the recovery of LV function and high-energy phosphates (HEPs) was lower with an increased release of creatine kinase (CK) during reperfusion than in the young group. The increased [Na+]i at the end of ischemia was greater in the former groups than in the young group. HP decreased myocardial glycogen and lessened the increased [Na+]i in the young group, resulting in an improved recovery of LV function and HEPs, as well as decreased CK release. However, the levels of glycogen before HP in the older groups were higher than in the young group and its levels after HP were similar to that before HP in the young group. HP did not affect the [Na+]i, exacerbated CK release and inhibited the recovery of LV function and HEPs in the older groups.. HP failed to lessen the increased [Na+]i or to protect the aging hearts, probably due to the preexistence of increased glycogen level.

Topics: Aging; Analysis of Variance; Animals; Calcium; Chi-Square Distribution; Creatine Kinase; Glycogen; Homeostasis; Ischemic Preconditioning, Myocardial; Male; Myocardial Ischemia; Myocardium; Perfusion; Phosphates; Rats; Rats, Inbred F344; Sodium; Ventricular Dysfunction, Left

The aim of the present experimental study in the rat heart was to assess cardiac performance and metabolism in mild diabetes of 2 months' duration (postprandial blood sugar levels of 307 +/- 101 mg/dl and nearly normal fasting blood glucose of 102 +/- 40 mg/dl) using the working rat heart model at physiological workload with a perfusion time of 60 min. We also compared the effect of two forms of therapy for diabetes, islet transplantation and insulin therapy (s.c.), after 2 months. A 36% reduction in glucose utilization is metabolically characteristic for the diabetic heart, mainly caused by a 55% reduced glucose uptake (P < 0.001), but also by a nearly twofold increased lactate and pyruvate production (P < 0.001). This reduced carbohydrate metabolism is accompanied by a 37% reduction of oxygen uptake (P < 0.001) as well as a significant reduction in myocardial ATP and CP levels (P < 0.001), resulting in a significantly reduced cardiac output (P < 0.001). Moreover, the balance of energy reveals that the diabetic heart obtains 46% of its energy requirements for 1 h from endogenous glycogen, whereas the control heart obtains 91% of its energy needs (i.e. preferentially) from exogenous glucose (only 9% from endogenous glycogen). Both investigated therapeutic interventions led to a complete reversibility of the hemodynamic and metabolic alterations, indicating that the cause of diabetic cardiomyopathy in this model of mild and short-term diabetes is due to a defect in cardiac carbohydrate metabolism, which is correctable by insulin administration.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Cardiac Output; Cardiomyopathies; Diabetes Mellitus, Experimental; Energy Metabolism; Glucose; Glycogen; In Vitro Techniques; Insulin; Islets of Langerhans Transplantation; Lactates; Male; Myocardium; Oxygen Consumption; Phosphocreatine; Pyruvates; Rats; Rats, Inbred Lew; Triglycerides; Ventricular Dysfunction, Left