Myocardial Glycolysis Research Articles

ECG-changes in the fetal lamb during asphyxia in relation to beta-adrenoceptor stimulation and blockade.

Progressive changes in the S-T interval of the fetal electrocardiogram (FECG) were studied in 14 lamb fetuses, acutely exteriorized and subjected to graded hypoxia. The aims of the study were to investigate whether beta-adrenoceptor stimulation and hypoxia exerted additive or potentiating effects on the FECG and several cardiovascular parameters and whether the hypoxic changes of the FECG could be blocked by beta-adrenoceptor blocking agents. The FECG changes were studied in order to correlate them with cardiovascular function, as measured by heart rate, mean arterial pressure, end diastolic pressure, maximum dP/dt and combined cardiac output, estimated by the thermodilution method, as well as with blood gases, acid base status, blood lactate and glucose. Injections of small doses (0.02 to 0.4 microg kg-1 min-1) of isoprenaline induced the same pattern of changes in the FECG as we have previously recorded during hypoxia. By increasing the isoprenaline dose an increase in the duration of the FECG changes and amplitude of the T-wave changes was obtained. Propranolol was found to completely abolish the FECG changes induced by isoprenaline, as well as by mild hypoxia. During severe hypoxia the FECG changes could not be abolished by propranolol. Our previous findings indicated that the hypoxic changes could be regarded as a sign of myocardial glycolysis. Thus, the present finding that even small doses of isoprenaline given to the fetus, initiates the same pattern of FECG changes corroborate this hypothesis.

Metabolic effects of inosine and uridine in rabbit hearts and rat skeletal muscles

Because of their cardiotonic properties and their close relations with tissue energetic stores, we studied the inotropic and metabolic effects of inosine and uridine in isolated perfused rabbit hearts and incubated rat diaphragm muscles. Inosine and uridine in concentrations of 10 −5 M increased myocardial contractility, glucose uptake, myocardial glycolysis and the breakdown of ATP in rabbit hearts. Uridine also increased glycogen content, most probably due to a stimulation of glycogen synthesis by this nucleoside. Neither nucleoside had an effect on myocardial lipolysis. Similarly, inosine in concentrations of 10 −4 to 10 −6 M stimulated glucose uptake and the rate of glycolysis in incubated rat diaphragm muscles. On the other hand, uridine in concentrations of 10 −4 to 10 −6 M stimulated glucose uptake and the content of glycogen in diaphragm muscles. However, no effect of uridine on glycogen content was observed when these muscles were incubated in Krebs bicarbonate medium without glucose. The inotropic and metabolic effects of inosine, but not of uridine, were abolished in isolated rabbit hearts treated with 10 −5 M propranolol. Despite this inhibition, it seems unlikely that the action of inosine and uridine is mediated by endogenous catecholamines. On the other hand, their metabolic effects are similar to those of cardiac glycosides.

A study of the relationship between the electrocardiogram and hemodynamics in the fetal lamb during asphyxia.

Progressive changes in the S-T interval of the fetal ECG were studied in 22 lamb fetuses, acutely exteriorized and submitted to graded hypoxia. The ECG changes were studied in order to correlate them with cardiovascular function, as measured by heart rate, mean arterial pressure, end diastolic pressure and combined cardiac output, estimated by the thermodilution method, as well as with blood gases and acid-base status. Close correlations were obtained between PaO2, pH and base deficit and the severity of ECG changes, graded according to a scoring system. Alterations in the ECG pattern consistently preceeded signs of failing cardiovascular function. Our previous findings indicated that the hypoxic ECG changes could be regarded as a sign of myocardial glycolysis. Accordingly, similar progressive ECG changes could be induced by isoprenaline injections. It is concluded that progressive changes of the S-T interval of the fetal ECG contains information about fetal hypoxic stress before signs of failing cardiovascular function are seen.

Changes in the ECG and Somatosensory-Evoked EEG Responses during Intrauterine Asphyxia in the Sheep

Progressive changes in the S-T interval of the fetal ECG were studied in 14 mature lamb fetuses, acutely exteriorized and submitted to a graded hypoxia. The degree of hypoxic stress was measured from changes in the somatosensory-evoked EEG responses (SER), blood gas analysis and lactate concentration. The ECG and the SER were found to be affected simultaneously. A close relationship was further obtained between pH of the arterial blood and changes in the S-T interval, the ratio between the T and S waves being used for quantifying these changes. This relationship was further strengthened by the strong correlation obtained between the accumulation of lactate and the T/S ratio. The findings corroborate the hypothesis that the hypoxic changes in the ECG pattern could be regarded as a sign of myocardial glycolysis and early hypoxic stress.

Alterations in Fetal Heart Rate and ECG Correlated to Glycogen, Creatine Phosphate and ATP Levels during Graded Hypoxia

The depletion of glycogen, creatine phosphate and ATP in the fetal heart, liver and brain was studied in 40 mature guinea pig fetuses acutely exteriorized and submitted to a graded hypoxia. A strong linear correlation was found between an ECG scoring system, taking the severity of the ST-T changes into account, and the depletion of heart glycogen and creatine-P. ATP was unaffected until glycogen was almost depleted (25 % of initial value). At this point, brain and liver glycogen were also severely affected. Bradycardia (AV-block, type II) was strongly correlated to failing myocardial metabolism. It is concluded that the changes in the fetal ECG pattern could be regarded as a sign of myocardial glycolysis and early hypoxic stress.

The Depletion of Energy Rich Substances Correlated To Changes In Fetal Heart Rate And Ecg

Previous findings have indicated that changes in the fetal ECG convay information about fetal hypoxic stress, well in advance of any alteration in fetal heart rate and blood pressure. To define a possible relation between the ECG changes and myocardial metabolism, a study was performed on 40 mature guinea-pig fetuses acutely exteriorized and submitted to a graded hypoxia. The depletion of glycogen, creatinephosphate and ATP in the fetal heart, liver and brain was correlated to an ECG-scoring system taking the severity of the ST-T changes into account. A strong linear correlation was found between the ECG scores and the depletion of heart glycogen and creatine-P. The ATP was unaffected until the glycogen was depleted /25 % of initial value/. At this point, brain and liver glycogen were also severly affected. Bradycardia /AV-block, type II/ was strongly correlated to failing myocardial metabolism. It is concluded that the changes in the fetal ECG pattern could be regarded as a sign of myocardial glycolysis and early hypoxic stress.

Isolated Heart Perfusion Techniques for Rapid Screening of Myocardial Preservation Methods: Anoxia versus Ischemia

Isolated nonworking and working heart preparations are described and recent modifications that increase their reliability and scope are reviewed. Isolated perfused tissues are superior to other models for screening myocardial preservation techniques. The metabolic and functional differences between anoxia and ischemia are stressed, myocardial glycolysis is reviewed, and from basic studies potentially fruitful avenues for investigation of myocardial preservation techniques are outlined. Better application of available knowledge of myocardial metabolism could further reduce the risks of cardiac operation.

Cardiac Effects of Isoproterenol during Graded Myocardial Ischemia

Conflicting results of isoproterenol administration to patients with ischemic heart disease suggest that the effect of isoproterenol on cardiac function is related to the severity of myocardial ischemia. Myocardial oxygen consumption (MVO2) was therefore reduced by graded reductions in coronary blood flow before and after coronary administration of isoproterenol in 9 anesthetized dogs. When coronary blood flow was reduced by less than 50 per cent of control value, cardiac output and maximal value of left ventricular pressure rise (dP/dt) were higher with isoproterenol than without at similar values of MVO2. When coronary blood flow was further reduced, however, cardiac output and dP/dt were depressed by isoproterenol. Myocardial lactate production was at any MVO2 value higher during isoproterenol administration than during control periods, and stimulation of myocardial glycolysis by isoproterenol might –- at least in part –- explain an improved cardiac function during moderate ischemia. From these experim...

Effect of insulin on the performance and metabolism of the anoxic isolated perfused rat heart.

When the oxygen supply to the myocardium is compromised, glycolysis may provide the critical energy necessary for the heart's survival. We investigated whether insulin, through its effects on myocardial glycolysis, influences the performance and the metabolism of the perfused rat heart during anoxia. Hearts in a modified Langendorff apparatus were perfused for 30 minutes with anoxic media containing glucose (50-500 mg/100 ml) with and without insulin (100 munits/ml) or with anoxic media containing 200 mg glucose/100 ml and varying insulin concentrations (0.1-100 munits/ml). Hearts were paced, and left ventricular pressure, maximum rate of rise of left ventricular pressure, and lactate production were monitored. Increasing glucose concentration alone progressively enhanced performance and lactate generation in the beating anoxic heart. Addition of insulin resulted in significant increases in left ventricular performance and lactate production at all levels of glucose concentration. The myocardial content of high energy intermediates (creatine phosphate, adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate) after 30 minutes of anoxia was not altered by varying concentrations of glucose or insulin. To assess the effects of insulin and glucose in the absence of contraction, hearts were arrested with media containing a high potassium concentration (26 mEq/liter). Although lactate production was lower in arrested hearts than it was in beating hearts, it was enhanced by insulin. Insulin also produced significant increases in high-energy intermediates in arrested hearts. It was concluded that insulin increases the utilization of glucose and thus causes the enhancement of ventricular performance in the anoxic heart.

Some effects of bromotrifluoromethane inhalation on myocardial glycolysis

Bromotrifluoromethane (CBrF 3) would have considerable potential as a closed environment fire extinguishing agent, except for its membership in that large group of hydrocarbons capable of precipitating irregular heart action when inhaled by persons with elevated levels of blood epinephrine. These experiments were an effort to determine whether myocardial glycolysis was impaired in male Wistar rats breathing 79 21 CBrF 3 O 2 and challenged with 1-epinephrine in what would ordinarily constitute subtoxic doses. CNS effects were the major observations in rats exposed to both CBrF 3 and epinephrine; 17 of the 20 rats so exposed suffered respiratory arrest within 40 min, and several of them exhibited erratic, convulsive behavior prior to exhibiting respiratory difficulties. All control rats survived, and myocardial levels of glycolytic intermediates were compared in animals breathing air or CBrF 3 O 2 , with and without epinephrine challenge, using “crossover plots.” With air-epinephrine and CBrF 3-epinephrine there were crossovers (activation) at phosphofructokinase, and the general picture was consistent with the CBrF 3 induction of respiratory depression and hypoxia, resulting in the mobilization and intracellular accumulation of free fatty acids.

EFFECT OF HYPOTHERMIA ON MYOCARDIAL METABOLISM.

Effect of hypothermia of 25 C for 24 hr was determined on myocardial metabolism and efficiency in dogs fasted for approximately 15 hr and anesthetized with sodium pentobarbital. Coronary blood flow, cardiac output, myocardial oxygen and substrate utilization, and mechanical efficiency of the heart were determined at normal and reduced body temperatures. Prolonged reduction of myocardial temperature with concomitant reduction in coronary blood flow led to diminished oxygen and substrate utilization. Myocardial glycolysis began after 12 hr of cooling when pyruvate utilization stopped in negative balance. After 24 hr the heart stopped utilizing carbohydrates with negative arteriovenous differences for these substrates (in the presence of normal arterial carbohydrate levels), but continued to utilize nonesterified fatty acid. The coefficient of oxygen utilization for the heart increased following 24 hr of cooling, suggesting a relative state of myocardial hypoxia. The appearance of hypoxia and glycolysis during the late hours of cooling suggests that the limit of tolerance of the heart to cooling was near.