glycogen and Alkalosis

Four possible metabolic approaches to improving cardiac function in the presence of myocardial hypoxia have been considered. 1. It appears that there is increasing evidence which suggests that free fatty acids are harmful to the ischemic heart. 2. Although it has been demonstrated that Krebs cycle intermediates can result in anaerobic energy formation by the mitochondria, and under certain extreme conditions can lead to improved performance of the heart, the potential for a physiologically important effect of this approach is probably limited. 3. The protection of the ischemic or hypoxic heart by alkalosis may be a feasible approach. The major beneficial effect appears to be exerted through more efficient conversion of energy that is already available to contractile performance rather than by increasing energy supply. 4. There appears to be some real potential for improving cardiac energy delivery via the glycolytic pathway. Calculations based on isolated rat heart studies indicate that, at 50% oxygenation, glycolytic ATP generation could totally correct for the deficit in mitochondrial ATP formation. Therefore, it is in the area of overcoming the inhibition of glycolytic ATP formation and tapping this potential metabolic pathway that energy delivery may be restored toward normal in the hypoxic and perhaps the borderline zone of underperfusion in the ischemic heart. The problem of the ischemic inhibition of glycolysis may partially be overcome by creating extracellular alkalosis, but this presumption will have to be tested.

Topics: Adenosine Triphosphate; Alkalosis; Anaerobiosis; Animals; Energy Metabolism; Fatty Acids, Nonesterified; Glucose; Glycogen; Glycolysis; Heart; Hydrogen-Ion Concentration; Hypoxia; Mitochondria, Muscle; Myocardium; Reserpine; Stress, Mechanical

Topics: Acidosis, Renal Tubular; Adipose Tissue; Alkalosis; Animals; Antihypertensive Agents; Blood Volume; Clinical Trials as Topic; Diuretics; Erythrocytes; Ethacrynic Acid; Furosemide; Glucose; Glycogen; Humans; Hyperkalemia; Hypokalemia; Membrane Potentials; Potassium; Pyrazines; Sodium; Spironolactone; Triamterene

Sodium bicarbonate (NaHCO3) ingestion has been shown to increase both muscle glycogenolysis and glycolysis during brief submaximal exercise. These changes may be detrimental to performance during more prolonged, exhaustive exercise. This study examined the effect of NaHCO3 ingestion on muscle metabolism and performance during intense endurance exercise of approximately 60 min in seven endurance-trained men.. Subjects ingested 0.3 g.kg-1 body mass of either NaHCO3 or CaCO3 (CON) 2 h before performing 30 min of cycling exercise at 77 +/- 1% .VO(2peak) followed by completion of 469 +/- 21 kJ as quickly as possible (approximately 30 min, approximately 80% .VO(2peak)).. Immediately before, and throughout exercise, arterialized-venous plasma HCO3- concentrations were higher (P < 0.05) whereas plasma and muscle H+ concentrations were lower (P < 0.05) in NaHCO3 compared with CON. Blood lactate concentrations were higher (P < 0.05) during exercise in NaHCO3, but there was no difference between trials in muscle glycogen utilization or muscle lactate content during exercise. Reductions in PCr and ATP and increases in muscle Cr during exercise were also unaffected by NaHCO3 ingestion. Accordingly, exercise performance time was not different between treatments.. NaHCO3 ingestion resulted in a small muscle alkalosis but had no effect on muscle metabolism or intense endurance exercise performance in well-trained men.

Topics: Administration, Oral; Adult; Alkalosis; Bicarbonates; Bicycling; Glycogen; Humans; Hydrogen-Ion Concentration; Lactic Acid; Male; Muscle, Skeletal; Physical Endurance; Physical Fitness; Sodium Bicarbonate; Time Factors

The purpose of the study was to examine the roles of active pyruvate dehydrogenase (PDH(a)), glycogen phosphorylase (Phos), and their regulators in lactate (Lac(-)) metabolism during incremental exercise after ingestion of 0.3 g/kg of either NaHCO(3) [metabolic alkalosis (ALK)] or CaCO(3) [control (CON)]. Subjects (n = 8) were studied at rest, rest postingestion, and during constant rate cycling at three stages (15 min each): 30, 60, 75% of maximal O(2) uptake (VO(2 max)). Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ALK resulted in significantly (P < 0.05) higher intramuscular Lac(-) concentration ([Lac(-)]; ALK 72.8 vs. CON 65.2 mmol/kg dry wt), arterial whole blood [Lac(-)] (ALK 8.7 vs. CON 7.0 mmol/l), and leg Lac(-) efflux (ALK 10.0 vs. CON 4.2 mmol/min) at 75% VO(2 max). The increased intramuscular [Lac(-)] resulted from increased pyruvate production due to stimulation of glycogenolysis at the level of Phos a and phosphofructokinase due to allosteric regulation mediated by increased free ADP (ADP(f)), free AMP (AMP(f)), and free P(i) concentrations. PDH(a) increased with ALK at 60% VO(2 max) but was similar to CON at 75% VO(2 max). The increased PDH(a) may have resulted from alterations in the acetyl-CoA, ADP(f), pyruvate, NADH, and H(+) concentrations leading to a lower relative activity of PDH kinase, whereas the similar values at 75% VO(2 max) may have reflected maximal activation. The results demonstrate that imposed metabolic alkalosis in skeletal muscle results in acceleration of glycogenolysis at the level of Phos relative to maximal PDH activation, resulting in a mismatch between the rates of pyruvate production and oxidation resulting in an increase in Lac(-) production.

Topics: Adenine Nucleotides; Adult; Alkalosis; Biopsy; Exercise; Femoral Vein; Glucose; Glycogen; Humans; Hydrogen-Ion Concentration; Lactic Acid; Leg; Male; Muscle, Skeletal; Oxygen Consumption; Phosphorylases; Pyruvate Dehydrogenase Complex; Pyruvic Acid; Radial Artery; Sodium Bicarbonate

Forty spontaneously hypertensive rats (SHRs) and forty normotensive Wistar-ST rats (NRs) were used to assess the influence of anesthetics on myocardial and hepatic energy metabolism after hemorrhage. They were divided into five pairs of groups: a control group (pentobarbital 6 mg.100 g BW-1 ip), and four others which received 1.2% halothane, 2.2% enflurane, 1.4% isoflurane, and 3.3% sevoflurane, respectively. Following a 10 min stabilization period, blood (2 ml.100 g BW-1) was gradually withdrawn over a 5 min period from a femoral artery. Thirty min after the induction of hemorrhage, the heart and liver were removed and myocardial and hepatic metabolites (ATP, lactate, pyruvate and glycogen) were measured by enzymatic methods. There were no significant differences in myocardial metabolites among either the anesthetic groups or between SHRs and NRs. However, hepatic ATP levels in all SHR groups were significantly lower than those in NR groups. Moreover, ATP levels in the inhalation anesthetic groups of SHRs were significantly higher than that in the control group of SHRs. All inhalation anesthetics, especially isoflurane, may reduce metabolic deterioration of the liver during hemorrhage when compared to barbiturate anesthesia.

Topics: Adenosine Triphosphate; Alkalosis; Anesthesia, Inhalation; Anesthetics; Animals; Blood Pressure; Energy Metabolism; Enflurane; Ethers; Glycogen; Halothane; Heart; Hematocrit; Hemorrhage; Hypertension; Isoflurane; Lactates; Liver; Methyl Ethers; Myocardium; Pyruvates; Rats; Rats, Inbred SHR; Rats, Wistar; Sevoflurane

This study examined the effects of extracellular alkalosis on the metabolism and performance of perfused rat hindlimb muscles during electrical stimulation. Three acid-base conditions were used: control (C, normal acid-base state), metabolic alkalosis (MALK, increased bicarbonate concentration), and respiratory alkalosis (RALK, decreased PCO2). A one-pass system was used to perfuse the hindlimb via the femoral artery for 20 min at rest and during 5 min of tetanic stimulation via the sciatic nerve. The isometric tension generated by the gastrocnemius-plantaris-soleus muscle group was recorded. Arterial and venous perfusates were periodically sampled for substrate and metabolite measurements, and muscle samples were taken pre- and postperfusion. Peak isometric tensions in C, MALK, and RALK were similar: 3,367 +/- 107, 3,317 +/- 110, and 3,404 +/- 69 g, respectively. The rate of tension decay was also unaffected by alkalosis and represented 78 and 55% of the peak tension following 2 and 5 min of stimulation, respectively. Muscle O2 uptake, glycogen utilization, and total lactate (La-) production were similar following 5 min of stimulation in all conditions. However, alkalosis resulted in an enhanced La- release from working muscle (peak La- release: C, 15.5 +/- 1.1; MALK, 19.7 +/- 1.6; RALK, 18.3 +/- 2.2 mumol/min), and a 15-20% reduction in intramuscular La- accumulation. Alkalosis had no effect on muscle creatine phosphate and ATP concentrations. Thus, in the perfused rat hindlimb, alkalosis was not associated with changes in tetanic force or glycolysis, but La- release from the working muscle was enhanced by increased extracellular pH and bicarbonate.

Topics: Alkalosis; Animals; Glucose; Glycogen; Isometric Contraction; Lactates; Lactic Acid; Male; Muscles; Oxygen Consumption; Physical Exertion; Rats; Rats, Inbred Strains

Topics: Alkalosis; Animals; Blood Glucose; Diazoxide; Epinephrine; Glucagon; Glycogen; Heptoses; Hydrocortisone; Hypokalemia; Liver Glycogen; Male; Muscles; Potassium Deficiency; Rats

Topics: Acid-Base Equilibrium; Adenosine Triphosphate; Alkalosis; Animals; Bicarbonates; Carbon Dioxide; Carbon Isotopes; Glucose; Glycogen; Glycolysis; Hydrogen-Ion Concentration; In Vitro Techniques; Lactates; Male; Myocardium; Phosphocreatine; Phosphofructokinase-1; Rats

Topics: Acidosis; Adolescent; Alkalosis; Child; Dehydration; Glycogen; Humans; Hyponatremia; Infant; Infant, Newborn; Metabolism; Parenteral Nutrition; Physiology; Potassium; Potassium Deficiency