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Mitochondrial oxygen consumption is synergistically inhibited by metallothionein and calcium.

OBJECTIVE: To determine the combined effect of metallothionein and calcium on the oxygen consumption of mitochondria. BACKGROUND: We previously showed that mitochondrial oxygen consumption was inhibited by the intracellular acute-phase reactant, metallothionein, which is rapidly induced by nearly all stressed cells. Other investigators have demonstrated that calcium also inhibited oxygen consumption. However, the calcium concentrations used in their experiments were supraphysiologic. Our hypothesis was that metallothionein would enhance the effect of calcium. METHODS: We conducted these experiments, of a paired design, on the effects of combinations of metallothionein and calcium using mitochondria isolated from rat liver. An oxygen electrode implanted into a 600-microliter chamber with a stir bar was used to measure oxygen consumption. Various concentrations of calcium, metallothionein, and other reagents were added while oxygen consumption was being continuously recorded. Metals were removed from metallothionein by gel filtration to produce apometallothionein. RESULTS: Physiological levels of metallothionein synergistically enhanced the inhibitory effect of calcium so that its action occurred at physiological concentrations. Metallothionein devoid of its metals, zinc and cadmium, had no effect on oxygen consumption. CONCLUSION: In isolated mitochondria metallothionein inhibits ADP-initiated oxygen consumption. This effect is synergistic with the inhibitory action of calcium. These observations suggest a possible enhancement by metallothionein of the effect of fluxes in intracellular calcium in stressed cells.

Adenosine Diphosphate↗

Estimated hepatic oxygen consumption in patients with chronic liver diseases as assessed by organ reflectance spectrophotometry.

We investigated the estimated hepatic oxygen consumption by reflectance spectrophotometry during peritoneoscopy and the rate of in vitro oxygen consumption of liver slices obtained by liver biopsy using the oxygen electrode apparatus in patients with chronic liver diseases. The estimated hepatic oxygen consumption decreased concomitantly with the decrease in blood supply, expressed as the regional hepatic blood hemoglobin concentration, and it was significantly decreased in cirrhosis compared to chronic hepatitis. The estimated hepatic oxygen consumption also was significantly correlated with the serum albumin level, 15-min retention rate of indocyanine green, and prothrombin time. There was no correlation between the estimated hepatic oxygen consumption calculated from the reflectance spectra and the rate of in vitro oxygen consumption measured by the oxygen electrode apparatus. Most cirrhotic liver slices had a respiratory rate comparable to that in chronic hepatitis. Thus, it is concluded that the reduction of estimated hepatic oxygen consumption in cirrhosis of the liver is mainly due to the reduction of oxygen supply secondary to the decrease of hepatic blood flow.

Adult↗

Alterations in cardiac oxygen consumption under chronic pressure overload. Significance of the isoenzyme pattern of myosin.

Hypertension and resulting left ventricular hypertrophy was induced in young male Wistar rats (60 to 70 days old) by narrowing of one renal artery (Goldblatt II). 8 and 24 weeks after operation, myocardial oxygen consumption was measured on a modified in situ heart-lung preparation with nearly isovolumetric left ventricular contractions. Measured myocardial oxygen consumption was related to left ventricular wall stress. The myosin isoenzyme pattern of each heart was determined with pyrophosphate gel electrophoresis. Oxygen consumption related to wall stress averaged over the entire heart cycle amounted to 15 mumoles O2/g X min 8 weeks after operation, and 24.4 mumoles O2/g X min in age-matched controls (delta 38%, p less than 0.0005). When wall stress was averaged over systole, oxygen consumption of the hypertrophied hearts amounted to 0.112 mumoles O2/g x beat, and 0.149 mumoles O2/g x beat in the controls (delta 25%, p less than 0.05). The proportion of VM-3 (the cardiac myosin isoenzyme of lowest ATPase activity) increased from 26.3% in the controls to 30.1% in the Goldblatt hearts (delta 14%, n.s.). 24 weeks after operation, oxygen consumption related to wall stress averaged over the entire heart cycle amounted to 16.1 mumoles O2/g x min, in age-matched controls 20.5 mumoles O2/g x min (delta 21%, p less than 0.05). When wall stress was averaged over systole, oxygen consumption of the Goldblatt hearts amounted to 0.080 mumoles O2/g x beat, and in the controls 0.107 mumoles O2/g x beat (delta 25%, p less than 0.0005). The proportion of VM-3 increased from 33.5% in the controls to 43.2% in the hypertrophied hearts (delta 29%, p less than 0.05). The present findings indicate that the reduced oxygen consumption of the pressure-loaded heart should be attributed to a redistribution of myosin isoenzymes. The transformation of myocardium into a slower, but more efficiently working muscle due to an increase in VM-3 can be interpreted as an adaptational process.

Animals↗

Oxygen consumption in infants and children during heart catheterization.

Oxygen consumption was measured in infants, children, and adolescents during diagnostic heart catheterizations. A total of 825 measurements of oxygen consumption (VO2) was performed in 504 subjects using a semiopen hood system and a paramagnetic oxygen analyzer. In 256 subjects under 3 years of age, body dimensions and heart rate were found to be significant factors for oxygen consumption. The regression equation for both sexes was: VO2/BSA (ml/min.m2) = 3.42.height (cm) - 7.83.weight (kg) + 0.38.HR - 54.1 (r2 = 0.39, SD = 38.7), where BSA is body surface area and HR is heart rate. VO2/BSA was significantly lower in infants less than 3 months of age (133 +/- 33 ml/min.m2) compared with infants of 3-12 months (171 +/- 37 ml/ min.m2; p < 0.01). In 272 children aged 3 years and older and adolescents, gender was a significant factor in oxygen consumption together with BSA and HR. The regression line equation for males was VO2/BSA (ml/ min.m2) = 0.79.HR - 7.4.BSA(m2) + 108.1 (r2 = 0.45, SD = 34.2). The regression line equation for females is VO2/BSA (ml/min.m2) = 0.77.HR - 5.2.BSA(m2) + 106.8 (r2 = 0.43, SD = 34.4). Hematocrit, systemic oxygen saturation, and blood pressure were not significant factors. The predictive value of nomograms for oxygen consumption is limited because of the large interindividual variations not explained by differences in gender, body size, or simple hemodynamic variables. Preferably, oxygen consumption is measured; but if nomograms for oxygen consumption are used for hemodynamic assessment, the wide confidence intervals should be considered.

Adolescent↗

Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans.

OBJECTIVE: Imbalance in the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischemic acute renal failure. Human atrial natriuretic peptide (h-ANP) increases glomerular filtration rate in clinical acute renal failure. This would increase renal oxygen consumption due to increased tubular load of sodium. Loop diuretics are commonly used in acute renal failure. Data on the effects of loop diuretics on glomerular filtration rate and renal oxygen consumption in humans are, however, controversial. We evaluated the effects of h-ANP and furosemide on renal oxygen consumption, glomerular filtration rate, and renal hemodynamics in humans. DESIGN AND SETTING: Prospective two-agent interventional study in a university hospital cardiothoracic ICU. PATIENTS: Nineteen uncomplicated, mechanically ventilated postcardiac surgery patients with normal renal function. INTERVENTIONS: h-ANP (25 and 50 ng/kg per minute, n=10) or furosemide (0.5 mg/kg per hour, n=9). MEASUREMENTS AND RESULTS: Renal plasma flow and glomerular filtration rate were measured using the infusion clearance technique for (51)Cr-labeled EDTA and paraaminohippurate, corrected for by renal extraction of PAH. h-ANP increased glomerular filtration rate, renal filtration fraction, fractional excretion of sodium, and urine flow. This was accompanied by an increase in tubular sodium reabsorption (9%) and renal oxygen consumption (26%). Furosemide infusion caused a 10- and 15-fold increase in urine flow and fractional excretion of sodium, respectively, accompanied by a decrease in tubular sodium reabsorption (-28%), renal oxygen consumption (-23%), glomerular filtration rate and filtration fraction (-12% and -7%, respectively). CONCLUSIONS: The filtered load of sodium is an important determinant of renal oxygen consumption. h-ANP improves glomerular filtration rate but does not have energy-conserving tubular effects. In contrast, furosemide decreases tubular sodium reabsorption and renal oxygen consumption and thus has the potential to improve the oxygen supply/demand relationship in clinical ischemic acute renal failure.

Acute Kidney Injury↗

Oxygen consumption by lungs with acute and chronic injury in a rabbit model.

OBJECTIVE: To study the oxygen consumption by lungs with acquired acute and chronic injury in a rabbit model. DESIGN: A non-randomized controlled animal study. SUBJECTS AND METHOD: Three groups of White New Zealand rabbits were studied to determine the oxygen consumption of the lungs. Group 1 (n=21, controls) consisted of healthy rabbits with normal lungs. The rabbits in group 2 (n=14) had sustained acute lung damage induced by subcutaneous N-nitroso-N-methylurethane and those in group 3 (n=9) had sustained chronic lung damage inflicted by a single dose of intra-tracheal bleomycin. Pulmonary oxygen consumption was estimated from the difference between the whole body oxygen consumption, measured by indirect calorimetry, and systemic oxygen consumption estimated by the Fick method. MEASUREMENTS AND RESULTS: Both acute and chronic lung-damaged groups had significantly greater pulmonary oxygen consumption than the control group, both as absolute values [control vs acute vs chronic: 0.25 (0.04) vs 0.76 (0.10) vs 1.77 (0.21) ml/kg per min, p<0.001], and as a percentage of total body oxygen consumption [2.98 (0.47) vs 9.34 (1.39) vs 20.20 (2.11)%, p<0.0001]. Histological evaluation of the severity of lung damage using a lung-injury score revealed significantly higher scores in both lung-injury groups than in the controls. CONCLUSIONS: These findings suggest that the lung is an important site of energy loss in subjects with acute and chronic lung injury.

Acute Disease↗

Oxygen delivery and consumption in critically ill pregnant patients: association with ophthalmic artery diastolic velocity.

OBJECTIVES: We aimed to investigate the relation between orbital vessel flow velocity and oxygen delivery, oxygen consumption, cardiac index, and systemic vascular resistance index in critically ill pregnant patients. STUDY DESIGN: Eighteen pregnant or early postpartum patients requiring invasive monitoring were prospectively studied with Doppler ultrasonography. The blood flow velocity and resistance index from the central retinal and ophthalmic arteries were plotted against the oxygen delivery index, oxygen consumption index, cardiac index, and systemic vascular resistance index. Linear and polynomial regression analysis and receiver-operator characteristic curves were used to examine the data. RESULTS: The ophthalmic artery resistance index correlated with oxygen consumption, oxygen delivery index, and cardiac index. Only the cardiac index was independently related to the the ophthalmic artery resistance index. The ophthalmic artery diastolic velocity correlated with oxygen consumption index, oxygen delivery index, and cardiac index. The ophthalmic artery diastolic velocity correlated independently with mixed venous oxygen content and arteriovenous oxygen content difference. The central retinal artery Doppler index did not correlate with any of the invasively measured parameters. An ophthalmic artery diastolic velocity of > 7.12 cm/sec identified 75% of patients with an oxygen consumption index of < 140 ml/min per square meter and 91% of patients with an oxygen delivery index of < 600 ml/min per square meter. CONCLUSIONS: These data suggest that the ophthalmic artery flow velocity is correlated with systemic oxygen delivery and consumption. This relationship may have potential research applications in the noninvasive assessment of oxygen delivery index and oxygen consumption index in critically ill pregnant patients.

Adolescent↗

Effect of selective blockade of oxygen consumption, glucose transport, and Ca2+ influx on thyroxine action in human mononuclear cells.

The effect of selective blockade of cellular glucose transporters, Ca2+ influx, and mitochondrial oxygen consumption on thyroxine (T4)-stimulated oxygen consumption and glucose uptake was examined in human mononuclear blood cells. Blockade of glucose transporters by cytochalasin B (1 x 10(-5) mol/L) and of Ca2+ influx by alprenolol (1 x 10(-5) mol/L) and verapamil (4 x 10(-4) mol/L) inhibited T4-activated glucose uptaken and reduced T4-stimulated oxygen consumption by 20%. Uncoupling of mitochondrial oxygen consumption by azide (1 x 10(-3) mol/L) inhibited T4-stimulated oxygen consumption, but had no effect on glucose uptake. We conclude that T4-stimulated glucose uptake in human mononuclear blood cells is dependent on intact glucose transporters and Ca2+ influx, but not on mitochondrial oxygen consumption. However, oxygen consumption is, in part, dependent on intact glucose uptake.

Adult↗

Oxygen consumption in Plasmodium berghei-infected murine red cells: a direct spectrophotometric assay in intact erythrocytes.

A spectrophotometric assay has been devised to measure oxygen consumption non-invasively in intact murine red cells parasitized by Plasmodium berghei. The method uses oxyhemoglobin in the erythrocytes both as a source of oxygen and as an indicator of oxygen consumption. Spectra of intact cells show broad peaks and sloping baselines due to light-scattering. In order to ascertain the number of varying components in the 370-450 nm range, the resolution of the spectra was enhanced using Fourier transforms of the frequency domain spectra. Calculation of oxygen consumption was carried out for two-component systems (oxyhemoglobin, deoxyhemoglobin) using absorbances at 415 and 431 nm. Samples prepared from highly parasitized mice (greater than 80% parasitemia, 5% hematocrit) showed oxygen consumption rates of (4-8) X 10(-8) microliter/cell per h. This rate was not attributable to the presence of white cells or reticulocytes. The rate of oxygen consumption in the erythrocytes is shown to be modulated by various agents: the respiratory inhibitors NaN3 and KCN (1 mM) reduced oxygen consumption 2-3-fold; salicylhydroxamic acid (2.5 mM) caused a 20% reduction in rate and 10 mM NaN3, completely blocked deoxygenation. Antimalarial drugs and metal-chelating agents were also tested. Chloroquine, EDTA and desferal (desferoxamine mesylate) did not decrease the deoxygenation rate of hemoglobin in parasitized cells. Quinacrine, quinine and primaquine reduced the rate of formation of deoxyhemoglobin but also produced substantial quantities of methemoglobin. The lipophilic chelator, 5-hydroxyquinoline, decreased the rate of deoxygenation one-third. The spectrophotometric assay provides a convenient means to monitor oxygen consumption in parasitized red cells, to test the effects of various agents thereon, and potentially to explore possible mechanisms for oxygen utilization.

Animals↗

Effect of AF64A on cerebral oxygen consumption in young and old rats.

Regional brain O2 consumption was determined in conscious Fischer-344 rats 3- and 33-months of age after intrahippocampal injection of the selective presynaptic cholinergic neurotoxin AF64A to investigate the influence of acetylcholine on this parameter. Regional cerebral blood flow (rCBF) was determined with 14[C]-iodoantipyrine. Regional arterial and venous oxygen saturation was measured microspectrophotometrically. Regional cerebral oxygen consumption was calculated by multiplying rCBF and cerebral oxygen extraction. Systemic hemodynamic and blood gas parameters were not altered by aging or AF64A. Aging or sham injection per se did not have any significant effect on rCBF, oxygen extraction and cerebral oxygen consumption. In 3-month-old AF64A-treated rats, rCBF, oxygen extraction or cerebral oxygen consumption were significantly lower than in the control group of the same age. Old AF64A-treated animals demonstrated a significant decrease in rCBF and cerebral oxygen consumption but not in cerebral oxygen extraction when compared to the sham-lesioned group of the same age. Oxygen consumption was significantly decreased by AF64A in each examined region of both young and old groups of rats, although the decreases were less severe in the older rats. This may be related to the lesser influence of the cholinergic system on cerebral oxygen consumption in old animals or a decreased toxicity of AF64A in older animals.

Aging↗

Continuous measurement of oxygen consumption during cardiopulmonary bypass: description of the method and in vivo observations.

BACKGROUND: Systemic oxygen consumption is not routinely measured during cardiopulmonary bypass, despite its potential benefits. We aimed to develop a noninvasive method to continuously measure oxygen consumption using respiratory mass spectrometry during hypothermic cardiopulmonary bypass in pigs. METHODS: Nine pigs weighing 18.5 (1.6) kg underwent hypothermic (32 degrees C) cardiopulmonary bypass for 180 minutes with 120 minutes of aortic cross clamping. An AMIS 2000 mass spectrometer (Innovision A/S, Odense, Denmark) was adapted for the on-line measurement of oxygen consumption by sampling the inlet and outlet gases of the membrane oxygenator together with measurement of the "expired" gas volume. RESULTS: Active cooling for 60 minutes reduced the venous blood temperature by 2.9 (0.8) degrees C and VO(2) by 0.70 (0.33) mL/kg/min. The 40-minute active rewarming restored the venous blood temperature by 4.4 (0.4) degrees C and oxygen consumption increased by 1.36 (0.33) mL/kg/min. There was wide interanimal variability, however, particularly at higher venous blood temperatures. Immediately after the release of aortic cross clamp, there was a noticeably acute increase in oxygen consumption in all the pigs (0.64 [0.21] mL/kg/min). CONCLUSIONS: A simple and safe adaptation of mass spectrometry allows continuous measurement of oxygen consumption during hypothermic cardiopulmonary bypass. The wide interindividual variations observed in this pilot study underscore the need to more accurately describe changes in oxygen consumption and how they are affected by temperature, oxygen delivery, and other interventions during cardiopulmonary bypass. As such, the technique may have an important role in clinical research and management of oxygen transport in patients undergoing cardiac surgery.

Animals↗

Oxygen consumption and chloride secretion in rat distal colon isolated mucosa.

The aerobic metabolic cost of chloride secretion was studied in rat distal colon isolated mucosa under several conditions by simultaneous measurement of short-circuit current and oxygen consumption under conditions that preserve vectorial ion transport. A low-chloride solution and the presence of bumetanide plus diphenylamine-2-carboxylate reduced short-circuit current by 75% and oxygen consumption by 25%. Ouabain decreased short-circuit current by 93% and oxygen consumption by 32%. Serotonin increased both variables by 59% and 33%, respectively. Bumetanide and diphenylamine-2-carboxylate reduced but did not abolish the effect of serotonin on short-circuit current and oxygen consumption. Changes in short-circuit current and oxygen consumption were linearly correlated under all conditions tested. It is concluded that, in the unstimulated rat distal colon epithelium, chloride secretion accounts for about 75% of ouabain-sensitive short-circuit current and oxygen consumption. Stimulated chloride secretion may demand over 40% of total oxygen consumption.

Animals↗

Reduced oxygen consumption induced by vasopressin in dogs depends on systemic administration.

1. Arginine vasopressin reduces whole-body oxygen consumption in conscious dogs. To determine whether this decrease could result from limited oxygen delivery, studies were performed in two groups of chronically instrumented dogs. 2. In the first group (n = 7), vasopressin was infused at a rate of 18.5 pmol min-1 kg-1 while the animals were breathing 10% oxygen. Hypoxaemia alone (arterial partial pressure of oxygen 4.67 kPa) decreased whole-body oxygen delivery by 30%. The fall in whole-body oxygen consumption induced by vasopressin during hypoxaemia was not different from that measured under normoxic conditions, even though whole-body oxygen delivery was more reduced. 3. In a second group of seven dogs, hindquarter blood flow (electromagnetic flowmeter on lower abdominal aorta) and oxygen consumption (blood flow multiplied by arteriovenous oxygen difference) were measured as infusions of vasopressin were given either systemically or into the lower abdominal aorta. Systemic vasopressin infusions at 0.92, 4.6 and 18.5 pmol min-1 kg-1 reduced hindquarter blood flow, oxygen delivery and oxygen consumption, but the decreases in blood flow and oxygen delivery were dose-related whereas that in oxygen consumption was not. Intra-arterial infusions of vasopressin that increased venous concentrations as much as or more than systemic infusion of 0.92 pmol of vasopressin min-1 kg-1 had no effect on oxygen consumption, even though the higher intra-arterial rate reduced blood flow and oxygen delivery as much as the systemic infusion. Thus systemic but not locally administered vasopressin reduced hindquarter oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Energetics of sodium transport in frog skin. I. Oxygen consumption in the short-circuited state.

Sodium transport and oxygen consumption were studied simultaneously in the short-circuited frog skin. Sodium transport was evaluated from I(o)/F, where I(o) is the short-circuit current measured with standard Ringer's solution bathing each surface and F is the Faraday constant. Oxygen tension was measured polarographically. Under a variety of circumstances the rate of oxygen consumption from the outer solution exceeded that from the inner solution, the ratio being constant (0.57 +/- 0.09 SD). Both I(o) and the associated rate of oxygen consumption J(ro) declined nonlinearly with time, but the relationship between them was linear, suggesting that the basal oxygen consumption was constant. For each skin numerous experimental points were fitted by the best straight line. The intercept (J(ro))(Io=0) then gave the basal oxygen consumption, and the slope dNa/dO(2) gave an apparent stoichiometric ratio for a given skin. The basal oxygen consumption was about one-half the total oxygen consumption in a representative untreated short-circuited skin. Values of dNa/dO(2) in 10 skins varied significantly, ranging from 7.1 to 30.9 (as compared with Zerahn's and Leaf and Renshaw's values of about 18). KCN abolished both I(o) and J(ro). 2,4-dinitrophenol (DNP) depressed I(o) while increasing J(ro) four- to fivefold. Anti-diuretic hormone stimulated and ouabain depressed both I(o) and J(ro); in both cases apparent stoichiometric ratios were preserved.

Animals↗

Heart rate and oxygen consumption of northern elephant seals during diving in the laboratory.

Many techniques have been employed to measure metabolic and cardiovascular changes in diving marine mammals. Each of these methods has its advantages, but the methods also have drawbacks when applied to phocid seals. The aim of this study was to investigate heart rate and metabolic responses to diving in juvenile northern elephant seals that are not associated with forced changes in exercise state, and, secondarily, to investigate whether heart rate could be used as an indicator of metabolic rate in this species. Six seals were allowed to dive freely in a metabolic chamber while simultaneous measurements of heart rate and oxygen consumption were made. Within each dive cycle (dive and surface interval), the seals spent an average of 74% of the time submerged. Mean dive duration was 6.43+/-0.6 (SD) min. Mean oxygen consumption during diving was 3.32+/-0.4 mL O2 min-1 kg-1, a decrease of approximately 26% from baseline values. An inverse relationship was observed between oxygen consumption and the percentage of time spent submerged in each dive cycle. The total amount of oxygen consumed during the surface interval increased with increasing dive duration, while the duration of the surface interval itself did not change, indicating that seals alter the rate of O2 uptake rather than the time spent at the surface. Mean heart rate during diving was 34.5+/-6.2 beats min-1, 36% lower than resting values. Mean diving heart rate was independent of dive duration, percent time submerged, and oxygen consumption. Mean surface interval heart rate was 66.6+/-11.1 beats min-1 and was not correlated with oxygen consumption. Average heart rate over the entire dive cycle increased with increasing oxygen consumption in all of the seals, but there was only a significant relationship in two seals, which casts some doubt on the usefulness of heart rate as an indicator of metabolic rate in this species. While providing important information on the changes in heart rate and oxygen consumption during diving in northern elephant seals, a complete understanding of the diving metabolic rate of these animals will require a combination of approaches that can be used in concert with data on freely living animals.

Animals↗

The effect of an herbal dietary supplement containing ephedrine and caffeine on oxygen consumption in humans.

OBJECTIVE: To determine if an herbal dietary supplement for weight loss increases metabolism. DESIGN: Measurement of peak oxygen consumption in response to the supplement followed by a double-blind placebo-controlled crossover measurement of oxygen consumption in response to the supplement. SETTING: The study was conducted in an academic research clinic. SUBJECTS: Ten obese females (aged 41 +/- 4 years [body mass index (BMI)] 33.3 +/- 2.6 kg/m2) participated in the peak oxygen consumption test; six of these females participated in the crossover trial. INTERVENTIONS AND OUTCOME MEASURES: Peak oxygen consumption was measured for 45 minutes after taking two herbal dietary supplement capsules orally, each containing the equivalent of 10 mg of caffeine and 5 mg of ephedrine. The crossover trial measured oxygen consumption for 45 minutes after taking two herbal dietary supplement capsules or two placebo capsules orally. RESULTS: The herbal dietary supplement increased peak oxygen consumption 0.178 +/- 0.03 (SEM) kcal/min (8.01 +/- 1.35 kcal/min expressed over 45 minutes) above baseline (p < 0.0001), and 2.0 +/- 0.56 kcal/min over 45 minutes compared to placebo (p < 0.006). CONCLUSIONS: The herbal dietary supplement increased oxygen consumption when taken according to the package directions. The significance of this rise for weight loss requires further research.

Caffeine↗

Effect of moderate arterio-venous shunt on regional extraction, blood flow and oxygen consumption in the dog heart.

The effects of a moderate sized arterio-venous shunt on the relationship of oxygen supply to consumption were studied on a regional basis in the dog left ventricle. Experiments were conducted on fourteen hearts, seven in control pentobarbital-anaesthetised, open-chest dogs and seven in dogs with an additional abdominal aorto-caval shunt. Regional oxygen extraction was determined by a microspectrophotometric method and coronary blood flow was measured with radioactive microspheres. The shunt, when opened, allowed cardiac output to increase by 50%. This was accomplished by increasing stroke volume, not heart rate. In control animals the subendocardium exhibited higher oxygen extraction, coronary flow, and oxygen consumption than did the subepicardium. There were no differences between base and apex. In open-shunt animals, subepicardial-subendocardial differences in extraction, flow and consumption were abolished. Subepicardial values for these in shunt animals were not different from the values obtained for the subepicardial values of controls. The subendocardium of shunt animals exhibited significant differences between base and apex for blood flow and oxygen consumption. There was a significant difference in subendocardial oxygen consumption between groups, the effect of the arterio-venous shunt being to reduce subendocardial consumption, especially in the apex, without reducing subepicardial oxygen consumption.

Animals↗

Relationship between local oxygen consumption and local and external cardiac work: effect of tachycardia.

This study was designed to determine the extent of coupling between regional myocardial segment work and corresponding regional oxygen consumption, and to examine whether tachycardia induced changes in regional work are translated into corresponding changes in external cardiac work. In the open chest anaesthetised dog, the heart was paced at frequencies of 120-270 beats.min-1. Global and regional myocardial O2 supply, consumption, and balance were evaluated at each heart rate, and correlated with corresponding functional changes. Global cardiac function was evaluated from aortic flow, blood pressure, and left ventricular pressure. Coronary sinus flow and O2 saturation were used to calculate O2 consumption. The integrated multiple of myocardial shortening (ultrasonic dimension crystals) by corresponding force (strain gauge arch) during an averaged beat was used to express regional segment work. Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry was used to evaluate O2 saturation in small arteries and veins. These indices were used to calculate regional myocardial oxygen consumption. NADH redox levels were recorded by surface fluorometry, and were found to increase with heart rate by up to 67%. Increasing heart rate from 120 to 180 beats.min-1 increased regional work from 3040(SEM 220) to a peak of 4290(280) mm.g-1.min-1, whereas external cardiac work did not increase [67.0(2.6) to 65.3(4.4) mm Hg.litre-1.min-1] and fell further at the highest rates. Regional oxygen consumption increased from 6.16(0.47) to 8.29(0.53) ml O2.min-1.100 g-1 and was linearly related to regional work at all heart rates (r = 0.971, p less than 0.05). External cardiac work fell by about 26% whereas global myocardial oxygen consumption increased by 49% during tachycardia. It is concluded that myocardial oxygen consumption is more closely related to regional segment work than to external work, and that tachycardia significantly raises the oxygen cost of external work of the heart.

Animals↗