glycogen and Cardiac-Output--Low

Myocardial preservation was assessed in 72 patients undergoing extensive myocardial revascularization. The patients were allocated at random to three surgical techniques: Group 1, intermittent aortic cross-clamping at 32 degrees C; Group 2, intermittent aortic cross-clamping at 25 degrees C; and Group 3, St. Thomas' Hospital cardioplegia. As intraoperative markers of ischemic damage, adenosine triphosphate, creatine phosphate, and glycogen contents were determined in transmural left ventricular biopsy specimens taken at the beginning and at the end of cardiopulmonary bypass. Ultrastructure was studied in a similar pair of biopsy specimens. Release of myocardium-specific creatine kinase isoenzyme was determined intraoperatively and postoperatively. Functional recovery was assessed before and after weaning from cardiopulmonary bypass. The incidence of low cardiac output, myocardial infarction, and rhythm disturbances was compared between groups. Finally, actuarial survival and event-free curves were studied after 18 months' follow-up. The results show a better preservation of high-energy phosphates, glycogen, and ultrastructure in the cardioplegia group as compared to the two cross-clamp groups. However, severe myocardial damage was never observed. Release of MB creatine kinase isoenzyme was the same in all three groups. Functional recovery of the hearts immediately after cessation of cardiopulmonary bypass was better in the cardioplegia group, but the incidence of rhythm disturbances (atrioventricular conduction problems) was higher in the cardioplegia group than in the other two groups (p less than 0.05). Clinical outcome in terms of incidence of perioperative infarction, survival, and event-free follow-up was not different between groups. It is concluded that both techniques (aortic cross-clamping at 32 degrees C or 25 degrees C and St. Thomas' Hospital cardioplegia) offer good myocardial protection in extensive aorta-coronary bypass operations. St. Thomas' cardioplegia, however, in contrast to intermittent aortic cross-clamping, prevents the onset of ischemia-induced deterioration of cardiac metabolism, i.e., destruction of the adenine nucleotide pool.

Topics: Adenosine Triphosphate; Adult; Aorta; Arrhythmias, Cardiac; Cardiac Output; Cardiac Output, Low; Cardiopulmonary Bypass; Clinical Trials as Topic; Constriction; Coronary Artery Bypass; Creatine Kinase; Follow-Up Studies; Glycogen; Heart Arrest, Induced; Hemodynamics; Humans; Intraoperative Complications; Isoenzymes; Myocardial Infarction; Myocardium; Phosphocreatine; Random Allocation

Ranolazine was previously shown to stimulate cardiac glucose oxidation. Dichloroacetate (DCA) also does and was shown to improve exercise capacity in animals, but it has long-term toxicity problems. To test the hypothesis that ranolazine would increase exercise performance in the chronic heart failure (CHF) condition, we compared the exercise endurance capacities of rats with a surgically induced myocardial infarction (MI) with those of noninfarcted sham-operated (Sham) controls both before and after 14 and 28 days of drug administration. Chronic administration of ranolazine, 50 mg/kg twice daily (b.i.d.) oral, significantly reduced the endurance capacities of both Sham and MI rats (measured after a 12-h fast to reduce liver glycogen stores), as indicated by the reductions in run times to fatigue during a progressive treadmill test. Ranolazine produced reductions in resting plasma lactate and glucose concentrations of animals fasted for 12 h (consistent with stimulating glucose oxidation); however, tissue glycogen concentrations measured in various locomotor muscles located in the animal's hindlimb were unaffected when measured 48 h after the last treadmill test and after 12 h of fasting. Chronic administration of ranolazine did not increase the endurance capacity of rats with CHF induced by MI at the dosage and with the protocol used. To the contrary, the chronic administration of ranolazine appears to reduce the work capacity of all rats, suggesting that this drug may not be useful therapeutically in the treatment of CHF. Whether the decrements in endurance capacity produced by ranolazine are related to the high plasma concentrations of the drug produced in this study as compared with previous studies in humans remains subject to further experimentation.

Topics: Acetanilides; Animals; Blood Glucose; Cardiac Output, Low; Enzyme Inhibitors; Female; Glycogen; Lactic Acid; Muscle, Skeletal; Myocardial Infarction; Physical Exertion; Piperazines; Ranolazine; Rats; Rats, Wistar

To better characterize the role of skeletal muscle in chronic heart failure we studied energetic charge, metabolites and enzyme activity in the energy production pathway. We selected 15 males with severe chronic heart failure (NYHA class III, stable clinical conditions and in normal nutritional status) and seven controls. Controls and patients were submitted to biopsy of the vastus lateralis muscle in resting and fasting conditions. Hormone profiles were also evaluated. Our results showed near normal ATP, ADP and AMP concentrations, but there were substantially more reductions in glycogen (46 +/- 5 vs 77 +/- 6 mumoles glycosidic units.g-1 fresh tissue) and creatine phosphate (5 +/- 1 vs 13 +/- 1 mumoles.g-1 fresh tissue) in patients than in controls. We also found a reduction in glycolytic activity (pyruvate kinase 1009 +/- 79 vs 1625 +/- 26 nmoles. min-1.mg protein-1), despite normal tricarboxylic acid cycle velocity, an increase in alanine amino-transferase (964 +/- 79 vs 425 +/- 34 nmoles. min-1.mg protein-1) and in aspartate aminotransferase (515 +/- 44 vs 291 +/- 56 nmoles.min-1.mg protein-1). An increase was also observed in total NADH cytochrome c reductase (128 +/- 14 vs 68 +/- 5 nmoles.min-1.mg protein-1), while cytochrome oxidase activity was normal. The cortisol/insulin ratio was slightly elevated (77 +/- 4 vs 32 +/- 12). In conclusion, normonutritive patients with severe heart failure show an imbalance in the energy production/utilization ratio. The impairment is probably due both to a decrease in production and an increase in consumption of energy owing to greater cellular workload and/or a hypercatabolic state.

Topics: Adenine Nucleotides; Biopsy; Cardiac Output, Low; Energy Metabolism; Fasting; Glycogen; Hormones; Humans; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine

Low cardiac output after heart surgery occurs more frequently in infants than in adults. This study was designed to determine whether this finding could be explained by a greater susceptibility of the immature heart to ischemia. An isolated working heart model was used to compare myocardial recovery in sets of hearts from six immature (2 weeks, 500 g) and six mature (20 weeks, 2 kg) rabbits after 10, 20, and 30 min of ischemia at 37 degrees C. Mean aortic pressure (MAP), aortic flow (AF), heart rate (HR), left atrial pressure (LAP), and ATP and glycogen levels were measured before and after ischemia. Hemodynamic results are expressed as the percentage recovery of preischemic values. ATP and glycogen are reported as micrograms per gram dry weight. After each period of ischemia, the immature hearts had superior recovery of AF (95 +/- 7.0, 72 +/- 8.8, 70 +/- 7.5 vs 58 +/- 7.1, 34 +/- 15.5, 13 +/- 9.1, P less than 0.05). After 10 min of ischemia, recovery of MAP was not different (97 +/- 1.5 vs 100 +/- 3.5), but after 20 and 30 min of ischemia, the immature hearts had better recovery of MAP (108 +/- 10.8, 98 +/- 5.4 vs 64 +/- 10.8, 48 +/- 6.0, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Aging; Animals; Cardiac Output, Low; Cardiac Surgical Procedures; Coronary Circulation; Glycogen; Heart; Hemodynamics; Myocardium; Rabbits

Topics: Blood Circulation; Blood Vessels; Cardiac Output; Cardiac Output, Low; Cardiovascular System; Glycogen; Humans; Hydrogen; Lactates; Lactic Acid; Muscles; Oxygen Consumption; Terminology as Topic; Vasodilator Agents

Light and electron microscopic study of the myocardium of dogs two weeks after clinical death caused by the loss of blood was carried out and showed that the structural bases of the myocardium contractile function insufficiency during the postresuscitation period included the damage of the contractile apparatus of cardiomyocytes (microlysis and fragmentation of myofibrils, deformation of Z-bands, relaxation of sacromeres) and marked lysis of the sacrotubular system leading to the violation of the excitation-contraction coupling. Cardiomyocyte damages are associated with changes in the microcirculatory channel causing the worsening of transcapillary exchange that provides the tissue homeostasis.

Topics: Animals; Cardiac Output, Low; Death, Sudden; Dogs; Glycogen; Microscopy, Electron; Myocardial Contraction; Myocardium; Oxidoreductases; Resuscitation; Time Factors

The role of the respiratory muscles in the evolution of experimental low cardiac output and lactic acidosis was studied in 2 groups of dogs. One group (6 dogs) was paralyzed and artificially ventilated, and the other (6 dogs) was breathing spontaneously. Shock was induced by cardiac tamponade; cardiac output during shock amounted to 25 to 35% of control values in both groups. All the spontaneously breathing dogs died from ventilatory failure (mean time, 2 h), whereas the artificially ventilated dogs were still alive 3 h after the onset of cardiogenic shock. At any given time after the onset of shock, arterial pH was significantly lower in the spontaneously breathing dogs than in the artificially ventilated ones. This was due to a greater increase in arterial blood lactate in the spontaneously breathing dogs than in the artificially ventilated ones (9.47 +/- 2.7 versus 4.74 +/- 56 mmoles/L at 2 h, respectively). Greater glycogen depletion associated with higher muscle lactate concentrations were found in the respiratory muscles of the spontaneously breathing dogs when compared with that in the artificially ventilated ones. It is concluded that artificial ventilation in cardiogenic shock decreases substantially the severity of lactic acidosis and prolongs survival.

Topics: Abdominal Muscles; Acidosis; Animals; Cardiac Output, Low; Diaphragm; Dogs; Glycogen; Intercostal Muscles; Lactates; Muscles; Respiration; Shock, Cardiogenic