Reduced Energy Supply Research Articles

'Myocardial hibernation'--questions and controversies.

Time for primary review 44 days. The term ‘hibernation’ has been borrowed from zoology and implies an adaptive reduction of energy expenditure through reduced activity in a situation of reduced energy supply. In the context of coronary artery disease, myocardial hibernation was originally seen as a chronic , adaptive reduction of myocardial contractile function in response to a reduction of myocardial blood flow. It was also viewed as a condition where there would be a complete recovery of contractile function upon restoration of flow. Thus, in the concept of myocardial hibernation, the observed chronic reduction of myocardial contractile function was not regarded as the result of a persistent energetic deficit, but instead as a regulatory event which acted to avoid an ongoing energy deficit and thereby maintain myocardial integrity and viability. The concept of myocardial hibernation did not originate in the laboratory, instead it was entirely founded on clinical grounds when, in the early eighties, Rahimtoola reviewed the results of coronary bypass surgery trials and identified a subset of patients with coronary artery disease and chronic left ventricular dysfunction that improved upon revascularization [1, 2]. Rahimtoola then popularized the term ‘hibernation’ previously coined by Diamond et al. [3]. Whereas originally the idea of an adaptive reduction of contractile function in response to a reduction in blood flow was straightforward and simple, the situation of chronic, yet reversible contractile dysfunction in the setting of coronary artery disease is now recognized to be enormously complex and controversial. The aim of this article is not to give definite answers to any questions, but rather to identify the most pressing questions and controversies in the field of hibernation. The introduction of the concept of hibernation has challenged the traditional view that the extent of chronic contractile dysfunction reflects the amount of infarcted … * Corresponding author. Abteilung fur Pathophysiologie, Zentrum fur Innere Medizin, Universitatsklinikum Essen, Hufelandstrase 55, 45122 Essen, Germany. Tel.: +49 (201) 7234480; fax: +49 (201) 7234481.

Effects of protein source and level on performance of lactating Damascus goats in negative energy balance

Effect of protein source (untreated soybean meal vs. formaldehyde-treated soybean meal) at three levels (13, 15 and 18% CP in the concentrate mixture, DM basis) on milk yield, milk composition, body weight (BW) change and rumen metabolites of 48 lactating Damascus goats was studied. Animals were fed to meet maintenance energy requirements and 60% of milk production energy requirements. Animals were housed and fed concentrates in groups of two animals, whereas roughage was offered to a single group per treatment. Goats consumed 0.175 kg barley hay and 0.269 kg barley straw/d. There were no significant effects of protein concentration or source on milk yield, milk composition, BW change and rumen metabolites. Protein source did not affect rumen NH 3-N and total VFA concentration, but dietary protein level had a significant effect ( P < 0.001) on rumen NH 3-N concentration. When all animals were changed to a higher feeding level at the end of the 42-d trial, milk yield was increased slightly; most of the extra feed allowance was directed towards weight gain. Formaldehyde (HCHO) treatment of soybean meal reduced degradability of DM (21 percentage units) and CP (19.2 percentage units) in the rumen. It was concluded that reduction in energy supply below requirements will result in considerably reduced milk yield, and that supply of a protein supplement of low degradability will not alleviate reduction in milk yield through greater mobilization of body reserves and subsequent use for milk production.

Acute adaptation to ischemia: short-term hibernating myocardium.

The term “hibernation” — a paradigm borrowed from zoology — implies a regulatory reduction of energy expenditure in adaptation to reduced energy supply, thereby allowing survival. In the heart, the situation of reduced contractile function (reflecting energy expenditure) during persistent reduction in blood flow (reflecting energy supply) was termed “myocardial hibernation”; by definition, the myocardium remains viable and contractile function recovers upon restoration of blood flow (4). While the initial period of adaptation to ischemia lasting for up to several hours, i.e., short-term myocardial hibernation, is well characterized in animal models, long-term myocardial hibernation lasting over weeks or months can only be inferred from clinical observations (4).

Cellular and Mechanical Effects of Myocardial Ischemia

Summary Myocardial pump failure during ischemia and hypoxia is often a reversible dysfunction. Contractile changes can occur in several different ways: during acute ischute ischemia, during chronic ischemia as an adaptive process, and during reperfusion following ischemia. Both systolic and diastolic contractile properties are impaired. Although a number of processes, e.g., the failure of the action potential generation mechanisms and reduced energy supply, have been suspected as causes of systolic impairment, the most likely factors appear to be H+ and inorganic phosphate concentrations. The increase in diastolic stiffness is most likely due to an increase in intracellular Ca2+ and, in severe instances, to rigor linkages between actin and myosin filaments. The extent of diastolic dysfunction depends on the nature of ischemia, being more marked in demand ischemia as compared with supply ischemia. Useful criteria to delineate the transition from reversible to irreversible ischemic damage are lacking. Nevertheless, assessment of the reversibility of ischemic contractile changes by nitroglycerin, inotropes, and postextrasystolic potentiation before surgical correction of the flow obstruction may have value in predicting outcome. Several adaptive biochemical changes are known to occur after stress. Hyperthermia produces a family of heat stress proteins that have been found to offer protection against ischemic cardiac damage. Future studies need to be performed to understand the mechanism of the regulation of production of these substances and how they afford protection to the ischemic myocardium. Furthermore, improvements in methods for imaging cardiac metabolic and perfusion status and the development of newer pharmacologic tools to alter intracellular pH regulation are expected to improve our understanding of the mechanism of ischemic cardiac damage and offer better possibilities of therapeutic management.

Extracellular sodium and chloride depletion enhances nonexocytotic noradrenaline release induced by energy deficiency in rat heart.

The effect of either extracellular sodium or extracellular chloride reduction on the release of endogenous noradrenaline and its deaminated metabolite dihydroxyphenylglycol (DOPEG) has been studied in the isolated perfused rat heart under conditions of ischaemia and cyanide intoxication. The overflow of noradrenaline and DOPEG was determined by high pressure liquid chromatography. The efflux of DOPEG, the predominant neuronal noradrenaline adrenaline metabolite, served as indicator of the free axoplasmic plasmic amine concentration. A calcium-free perfusion buffer was used to avoid exocytotic noradrenaline release. Sodium and chloride in the perfusion buffer were replaced by lithium and isethionate, respectively. (1) Reduction of extracellular sodium or chloride increased noradrenaline overflow in ischaemia. The release was suppressed by the uptake1 blocker cocaine indicating carrier-mediated outward transport of noradrenaline. (2) In cyanide intoxication sodium or chloride reduction accelerated the onset of DOPEG efflux reflecting increased axoplasmic noradrenaline concentrations. This was accompanied by increased noradrenaline release. The ratio of noradrenaline/DOPEG overflow was increased by reduced sodium or chloride, indicating facilitation of carrier-mediated noradrenaline net outward transport. (3) In the presence of unaltered energy metabolism overflow of both, noradrenaline and DOPEG, was not enhanced by sodium or chloride reduction. The results demonstrate that reduction of extracellular sodium or chloride has two effects on noradrenaline release from the sympathetic neuron with reduced energy supply. First, reduced sodium or chloride induces increased axoplasmic noradrenaline concentrations by interference with vesicular storage function. Second, both interventions enhance carrier-mediated noradrenaline release.

Metabolic and structural adaptations to exercise in chronic intermittent fasted rats.

The effect of repetitive alternance of 3 days fasting and 3 days refeeding on morphological and biochemical ability to perform exercise was investigated in adult male rats. At the end of 10 wk of chronic intermittent fasting, the rats had consumed 20% less food but were able to maintain their initial body weight. Intermittent fasted rats (IF) had significantly lower carcass fat but had maintained the percent contribution of proteins to total carcass weight. The relative mass of liver, heart, kidney, and muscles was not affected by such dietary manipulation. Both glycolytic and oxidative enzyme capacities were reduced in IF rat muscles. In response to exercise (2 h of swimming), control rats displayed hypoglycemia, whereas IF rats were able to maintain plasma glucose level in spite of a reduced energy supply from liver (low glycogen stores) and adipose tissue (low plasma free fatty acid levels). This had been obtained by accumulating glycogen and triglycerides in muscles and by deriving energy for muscular contraction from the in situ breakdown of these energetic substrates. In addition, although IF rats displayed a markedly reduced liver protein content, the liver exercise-induced protein breakdown was abolished in these animals.

Inhibition of spermatogenesis, motility and metabolic enzymes of sperm by gossypol.

Available data about gossypol a potential male antifertility agent explain its inhibition of spermatogenesis and possible mechanism of action. Spermatogenesis in rats has been inhibited by gossypol with no adverse effects on Leydig cells or Sertoli cells. The degree of damage to rat testes seminiferous epithelium was dose and duration related. Opinion varies regarding the site and mechanism of gossypols antifertility action. Early studies suggested an inhibition of the development of the spermatozoal nucleus and acrosome indicating a site of action for gossypol at the level of the testes but not the epididymis. Other studies did not confirm spermatozoal head defects but rather showed lesions in the spermatozoa tail in the epididymis. This discrepancy may indicate differences in spermatozoa response to gossypol with various mature stages. Other studies with rats and guinea pigs indicated an inhibitory action of gossypol preventing epididymal spermatozoa from attaining maturation. No consensus about the nature or site of gossypols antifertility action has been reached. In men the 1st effect of gossypol is a rapid loss of spermatozoa motility followed by a reduction of spermatozoa count. This decreased motility resulted from a reduction in energy supply through inhibition of glycolysis and the respiratory chain and the uncoupling of oxidative phosphorylation and reduction in ATP synthesis. The influence of gossypol on the tubulin-dynein system has recently been investigated in sea urchins. Gossypol has also been shown to inhibit the activity of several enzymes involved in energy metabolism including several dehydrogenases. Gossypol also decreased adenylate cyclase activity and inhibited fructolysis in human spermatozoa. Oral administration of gossypol at 12-30 mg/kg/day for 5-12 weeks induced infertility in rats hamsters guinea pigs dogs monkeys and men.

Commentary: Health Costs of a Reduced Energy Supply

Health effects associated with electricity production, especially air pollution from fossil fuel combustion, have received much attention in the past 30 years. Virtually no attention has been paid to the health costs of a reduced or overpriced energy supply although these are real and formidable. Stringent regulations mandating control technology on stack emissions and/or burning of low sulfur fuels have been promulgated which cost the American public billions of dollars. These have indeed alleviated some health problems, but pressures to further tighten regulations offer little chance of further health benefits commensurate with their cost and are most likely to produce a new series of problems.

Health costs of a reduced energy supply.

Health effects associated with electricity production, especially air pollution from fossil fuel combustion, have received much attention in the past 30 years. Virtually no attention has been paid to the health costs of a reduced or overpriced energy supply although these are real and formidable. Stringent regulations mandating control technology on stack emissions and/or burning of low sulfur fuels have been promulgated which cost the American public billions of dollars. These have indeed alleviated some health problems, but pressures to further tighten regulations offer little chance of further health benefits commensurate with their cost and are most likely to produce a new series of problems.

Energy conservation in solvent extraction

AbstractIncreased costs for energy and unpredictable supplies of fuel have created a new dimension in business management. Energy and solvent costs account for 40–50% of total costs in operating an oilseed solvent extraction plant in the USA. Many companies are finding that an organized energy conservation program can hold down both energy use and costs without disrupting plant production. It has been repeatedly demonstrated that conservation measures can reduce energy by 15–30% or more with justifying cost savings. More importantly, if by energy conservation you can maintain production despite a reduction in energy supply, or increase production in the face of frozen fuel allocations, the effect on your sales and profits is obvious.

METABOLIC PRIORITIES WITH RESPECT TO GROWTH AND MINERAL UPTAKE IN ROOTS OF HORDEUM, TRITICUM AND LYCOPERSICON

Reduction in the supply of photosynthate to the roots of tomato, barley, and wheat plants was achieved indirectly by lowering the intensity of sunlight striking the foliage of test plants. The decrease in sugar and starch concentrations in the roots was verified by appropriate extraction and colorimetric analysis, and a corresponding reduction in the total respiratory rate of the roots was confirmed using an oxygen tension monitor. Other processes measured directly include the rate of uptake of potassium, the mitotic quotient in the root tip—a measure of growth—and the rate of accumulation of dry matter in the root. The study demonstrated that of the metabolic activities observed, root growth is the process first limited when the supply of photosynthetic fuel is decreased. Root growth was severely inhibited under conditions that did not significantly affect either the active uptake of potassium per gram of root or total respiration per gram of root. With greater restriction of photosynthesis, growth was completely halted while the uptake of potassium was strongly decreased and total respiration was still affected only moderately. As the light intensity is reduced significantly, most of the reduced energy supply in the root appears to be used in support of processes critical to maintenance of the organ and the organism.

Metabolic Priorities with Respect to Growth and Mineral Uptake in Roots of Hordeum, Triticum and Lycopersicon

Reduction in the supply of photosynthate to the roots of tomato, barley, and wheat plants was achieved indirectly by lowering the intensity of sunlight striking the foliage of test plants. The decrease in sugar and starch concentrations in the roots was verified by appropriate extraction and colorimetric analysis, and a corresponding reduction in the total respiratory rate of the roots was confirmed using an oxygen tension monitor. Other processes measured directly include the rate of uptake of potassium, the mitotic quotient in the root tip—a measure of growth—and the rate of accumulation of dry matter in the root. The study demonstrated that of the metabolic activities observed, root growth is the process first limited when the supply of photosynthetic fuel is decreased. Root growth was severely inhibited under conditions that did not significantly affect either the active uptake of potassium per gram of root or total respiration per gram of root. With greater restriction of photosynthesis, growth was completely halted while the uptake of potassium was strongly decreased and total respiration was still affected only moderately. As the light intensity is reduced significantly, most of the reduced energy supply in the root appears to be used in support of processes critical to maintenance of the organ and the organism.

Energy-dependent phases of the circadian clock and the clock-controlled leaf movement in Phaseolus coccineus L.

The energy requirements of the various phases of the circadian clock in the laminar pulvini cells of primary leaves of Phaseolus coccineus L. were investigated using 4-h pulses of NaCN (5 mM) and NaN3 (1 mM). The induced phase shifts were calculated from the timing of the subjective night position during the third cycle after the treatment. Both inhibitors produce advances during phases which are correlated with the upward movement of the leaf (ca. 0-12 h after the maximum of the subjective night position) and during phases which are correlated with the downward movement of the leaf (ca. 20-28 h after the maximum of the subjective night position). Maximal advances are induced during the phase which is correlated with the maximum of the subjective night position (hour 0), whereas during phases which are correlated with the subjective day position (ca. 12-20 h after the maximum of the subjective night position) the inhibitors have no effect or induce only small advances. These results demonstrate that the part of the circadian cycle which, according to Bünning's tension-relaxation model of the circadian clock, is characterized by features of relaxation, represents a sequence of phases with decreasing energy requirement, whereas the tension part of the circadian cycle represents a sequence of phases with increasing energy requirement. The energy requirement for changing and maintaining the leaf positions was investigated by continuously offering NaCN, NaN3, and dinitrophenol (DNP) to leaves with intact and half (flexor cut away) pulvini. The substances inhibit in both pulvini the upward movement or induce a downward movement, depending on the leaf position, when the transfer to the inhibitor solution takes place. These results give evidence that the movement of intact pulvini reflects the turgor (volume) state of the extensor cells and that the increase of turgor (volume) and high turgor (volume) state requires more energy than the decrease of turgor (volume) or low turgor (small volume) state. Therefore, the time course of the energy requirements of the circadian clock and the clock-controlled turgor (volume states or leaf movement) is out of phase during a circadian cycle. Consequently the reaction of the clock-controlled leaf movement to the reduced energy supply can mask the clock behavior in pulse and step experiments. The phase response curves towards CN(-) and N 3 (-) reflect the time course of the CN(-)-induced membrane depolarizations (the energy requirement of the electrogenic pump) in extensor cells of the pulvinus (Freudling et al. (1980), Plant Physiol. 65, 966-968), and both are out of phase with the time course of the energy requirement of the turgor. Consequently it is hypothesized that in Phaseolus advances are due to membrane depolarization and that at least in this organism electric properties of the plasmalemma are essentially involved in the mechanism of the circadian clock.

Health effects associated with increased use of coal

The increased use of coal projected under the National Energy Plan has raised fears of increased morbidity and mortality related to fossil fuel combustion products. The evidence for adverse health effects from the major emissions of coal combustion is considered, as well as the basis for predictions of an increase in morbidity and mortality. It can be concluded that with presently available control technology, no detectable adverse health effects will be observed associated with increased coal combustion. It is further concluded that a reduction in energy supply, or a large increase in energy cost leading to reduced energy supply to lower socio-economic groups will cause far more demonstrable adverse health effects than increased coal utilization.

The potential for energy conservation in U.K. industry

The potential for energy conservation via the implementation of proven technology within United Kingdom industry is examined using a disaggregated model of individual industrial sectors, fuels supplied, and end-use energy purposes. Energy savings are quantified following the application of general and process-specific conservation measures. Overall, a 30% reduction in energy supply may be achieved at present output levels, varying from 22% in the Paper, Printing, and Stationery sector to 35% in the Food, Drink, and Tobacco inductries. Additionally, a pricing regime in favour of solid fuels is expected to effect a shift away from oil- and natural-gas consumption towards coal. With the advent of low-energy-intensive industries increasingly replacing traditionally high-energy-consuming operations such as iron and steel making, shipbuilding, and heavy engineering, there appears to be no reason for supposing that the continuing overall decline in the energy intensity of British industry will come to a halt. Industrial growth does not require profligate energy consumption.

Inhibition of fast axonal transport and microtubule polymerization in vitro by colchicine and colchiceine

The effects of colchicine and colchiceine on fast axonal transport in frog sciatic nerves were studied in vitro. Colchiceine inhibited the transport to about the same extent as colchicine. Preincubation at low temperature potentiated the inhibitory effect of either drug. The polymerization of purified brain tubulin was inhibited by colchiceine at 5-10 times higher concentrations than colchicine. The similarity of the effects obtained with colchicine and colchiceine indicates that both drugs arrest axonal transport by interfering with microtubule function. Colchicine and colchiceine did not affect the levels of high energy phosphates (ATP and CrP) in frog nerves indicating that a reduced energy supply was not responsible for the arrested transport.

Chloride transport and cation pump in Ehrlich ascites cells

It was investigated whether the movement of chloride ions through the osmotic barrier of Ehrlich cells is passive. i.e. driven by a membrane potential, which again is controlled by an active cation pump, or is active. Therefore, the distribution and the unidirectional fluxes of Cl−, along with the distribution of K+, Na+ and water between cells and medium, were measured while the cation pump was active (37°, Krebs‐Henseleit buffer, pH 7.4, 95% O2+ 5% CO2) and, for comparison, while the cation pump was inhibited by gassing with N2 instead of O2 or by adding DNP to the medium. In the presence of 1% bovine serum albumin, DNP altered the electrolyte levels inside the cell only at relatively high concentrations, 0.5–1 mM, then having the same effects as has anoxia. In either case, cells shrank by about 10%, attaining a new steady state which lasted for at least 20 min. K+ and Na+ gradients were than reduced to 2/3 and 1/2 of their normal values respectively. With cells thus shrunken and with control cells, exchange of cell chloride for labelled chloride in the medium reached an equilibrium after about 20 min. In the controls, the exchangeable fraction of total cell chloride, calculated by logarithmic extrapolation, amounted to 60–70% only (Hempling and Kromphardt [1]); the same fraction exchanged with nitrate in the medium. In cells treated with DNP or N2, the exchangeable fraction (for 36Cl) was still smaller: 45–55%. It seemed to be proportional to the water content of the cell. On the other hand, the non exchangeable chloride did not depend on cell water content nor did it change on DNP treatment or anoxia. It stayed fairly constant at 100 μequiv per g dry weight. Total cell chloride, however, increased again in direct proportion to the cell water (which varied spontaneously in different batches at the same medium osmolarity). It is concluded that the concentration of exchangeable chloride with respect to its corresponding cell compartment equals that of total chloride with respect to total cell water. On the basis of this assumption, the distribution ratio (cell: medium) of free exchangeable chloride was calculated to be 0.65 in control cells and 0.57 in cells with inhibited energy supply. Both unidirectional Cl− fluxes decreased in the last case to 30–50% of control; the 42K influx, however, measured simultaneously, was depressed more strongly than the 36Cl influx. This suggests that the inhibition of the cation pump is primary and that of chloride fluxes is secondary, i.e. that the chloride fluxes are passive and that chloride distributes according to the membrane potential. A measured potential, as reported by Hempling [2], agrees with this view. But the distribution of chloride and that of the sum of [Na+] + [K+] do not follow Donnan's law, suggesting that either the passive permeabilities or the pumped fluxes of the two cations must be different. Therefore the cation pump, be it electroneutral or electrogenic, must determine the potential in either case. Furthermore, since reduced energy supply diminishes Cl− influx and efflux while leaving the influx of the small neutral thiourea molecule unchanged, the cation pump must influence the passive permeability for ions specifically.

Hormonal regulation of liver hexokinase activity

Summary 1. In liver cells of the rabbit embryo hexokinase activity is much higher, its intracellular distribution being different from that found in mature animals (higher activity of hexokinase bound to mitochondria, occurrence of hexokinase in microsomes). Hexokinase activity of cell fractions decreases with embryonic age. Glucose-6-phosphate dehydrogenase activity of embryonic liver is also shown to be much higher than in adult rabbits and to decrease gradually towards term. Glucose-6-phosphatase activity is absent at early embryonic periods and shortly before birth, rising up to levels found in adult rabbits shortly after birth. 2. Absence of any “barrier” for penetration of glucose in liver cells provides favorable conditions for studying hormonal influences (glucocorticosteroids and insulin) on the activity of HK and other enzymes of liver glucose-6-phosphate metabolism. 3. Glucocorticoid (cortisone acetate) administration to adult rabbits and rats provokes inhibition of hexokinase and glucose-6-phosphate dehydrogenase dissolved in hyaloplasm of liver cells, inhibition of HK bound to mitochondria being more slow to set in. 4. 6. After cortisone acetate administration, hepatic glucose-6-phosphatase activity is shown to rise considerably, both in the adult animal and embryo. 7. Dissimilar reactivity to the effects of glucocorticoids displayed by hexokinase or glucose-6-phosphate dehydrogenase on one hand, and by glucose-6-phosphatase on the other, in cell fractions from embryonic liver, apparently depends on different mechanisms underlying the effects exerted by these hormones on activity or synthesis of the enzymes under consideration. 8. Hexokinase activity diminishes considerably in liver cell fractions from alloxan diabetic rabbits. Insulin administration restores mitochondrial hexokinase activity rapidly, while hexokinase dissolved in hyaloplasm is restored much more slowly. 9. The effect of insulin in vitro has been studied under conditions ensuring against its destruction by insulinase. Rapid reversal by insulin of the inhibiting influence of glucocorticoids on hepatic hexokinase and glucose-6-phosphate dehydrogenase activities of alloxan diabetic or of cortisonetreated animals, as well as reversal of their glucose-6-phosphatase enhancing influence, enzymatic activity tending to approach normal values have been demonstrated to occur in vitro . These facts provide evidence for a direct action of insulin on hepatic glucose-6-phosphate metabolism. 10. The inhibiting effect of cortisone (dissolved in β -lipoprotein) and of β -lipoprotein from blood plasma of alloxan diabetic or fasted animals on yeast hexokinase activity, as well as reversal of the inhibition by insulin, have been confirmed. Inhibition of yeast hexokinase by cortisone is shown to occur even after N-ethylmaleimide assay, binding SH groups of the enzyme. Cortisone inhibits phosphorylation of glucose and mannose by yeast hexokinase, but fails to influence phosphorylation of 2-desoxyglucose or fructose. Insulin produces rapid reversal of the inhibiting effect of cortisone on yeast hexokinase, activity of the enzyme being restored entirely. The influence of insulin fails to take place after the SH groups of hexokinase have been bound (by N-ethylmaleimide). Insulin may, therefore, be assumed to bind these groups of yeast hexokinase. 11. The block of hepatic glucokinase reaction occurring in diabetes results in a lowered level of energy metabolism and reduced energy supply to synthesis in the liver. 12. Primary disturbance of hepatic glucose-6-phosphate metabolism proves to be a significant factor in the onset of secondary metabolic disorders, affecting the organ and the body as a whole.