Tissue Oxygen Consumption Research Articles

Postmortem Oxygen Consumption by Mitochondria and Its Effects on Myoglobin Form and Stability

The objective of this study was to assess the morphological integrity and functional potential of mitochondria from postmortem bovine cardiac muscle and evaluate mitochondrial interactions with myoglobin (Mb) in vitro. Electron microscopy revealed that mitochondria maintained structural integrity at 2 h postmortem; prolonged storage resulted in swelling and breakage. At 2 h, 96 h, and 60 days postmortem, the mitochondrial state III oxygen consumption rate (OCR) and respiratory control ratio decreased with time at pH 7.2 and 5.6 (p < 0.05). Mitochondria isolated at 60 days did not exhibit ADP-induced transitions from state IV to state III oxygen consumption. Tissue oxygen consumption also decreased with time postmortem (p < 0.05). Mitochondrial oxygen consumption was inhibited by decreased pH in vitro (p < 0.05). In a closed system, mitochondrial respiration resulted in decreased oxygen partial pressure (pO(2)) and enhanced conversion of oxymyoglobin (OxyMb) to deoxymyoglobin (DeoMb) or metmyoglobin (MetMb). Greater mitochondrial densities caused rapid decreases in pO(2) and favored DeoMb formation at pH 7.2 in closed systems (p < 0.05); there was no effect on MetMb formation (p > 0.05). MetMb formation was inversely proportional to mitochondrial density at pH 5.6 in closed systems. Mitochondrial respiration in open systems resulted in greater MetMb and DeoMb formation at pH 5.6 and pH 7.2, respectively, vs controls (p < 0.05). The greatest MetMb formation was observed with a mitochondrial density of 0.5 mg/mL at both pH values in open systems. Mitochondrial respiration facilitated a shift in Mb form from OxyMb to DeoMb or MetMb, and this was dependent on pH, oxygen availability, and mitochondrial density.

Measured pulmonary oxygen consumption: difference between systemic oxygen uptake measured by the reverse Fick method and indirect calorimetry in cardiac surgery

Measurement of oxygen uptake by indirect calorimetry was compared with the reverse Fick method in a series of patients undergoing cardiac surgery. Oxygen uptake measurements for indirect calorimetry were made using a calibrated measurement system utilizing the Haldane transformation in a simple semiclosed breathing system based upon a modified Bain circuit. Pulmonary blood flow for the reverse Fick method was measured using bolus thermodilution. The results were (mean [standard deviation]): indirect calorimetry 167[26] ml.min(-1), and reverse Fick 148[27] ml.min(-1). Indirect calorimetry overestimated the reverse Fick value by 11.3% (p < 0.001). These results are consistent with the findings of previous studies in similar patient groups and are explained by lung tissue oxygen consumption.

Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution

Extreme hemodilution was performed in the hamster chamber window model using 6% Dextran 70, lowering systemic hematocrit by 60%. Animals were subsequently divided into three groups and hemodiluted to a hematocrit of 11% using 6% Dextran 70, 6% Dextran 500, and a 4% Dextran 70 + 0.7% alginate solution (n = 6 each group). Final plasma viscosities were 1.4 +/- 0.2, 2.2 +/- 0.1, and 2.7 +/- 0.2 cp, respectively, (P < 0.05, high viscosity vs. low viscosity). Blood viscosities were 2.1 +/- 0.2, 2.9 +/- 0.4, and 3.9 +/- 0.3 cp, respectively. The lowest blood and plasma viscosity group had a significantly lower functional capillary density, 37 +/- 16%, whereas the two high-viscosity solutions were 71 +/- 15% and 76 +/- 12% (P < 0.05, high viscosity vs. low viscosity), respectively. Arteriolar and venular flow in the Dextran 500 and alginate groups was higher than baseline (i.e., normal nontreated animals), whereas the low-viscosity group showed a reduction in flow. These microvascular changes were paralleled by changes in base excess, which was negative for the Dextran 70 group and positive for the other groups. However, tissue Po(2) was uniformly low for all groups (average of 1.4 mmHg). Calculation of tissue oxygen consumption in the window chamber based on the microvascular data, flow, and intravascular Po(2) showed that only the alginate + Dextran 70 solution-exchanged animals returned to baseline oxygen consumption, whereas the other groups were lower than baseline (P < 0.05). These results show that hemodilution performed with high-viscosity plasma expanders yields systemic arterial pressures and functional capillary densities that are significantly higher (P < 0.05) than those obtained with 6% Dextran 70, a fluid whose viscosity is similar to that of plasma. A condition for obtaining these results is that the oncotic pressure of the plasma expander be titrated to near normal, so that autotransfusion of fluid from the tissue into the vascular compartment does not reduce the effects of increasing plasma viscosity and increased shear stress on the microvascular wall.

Principle and technique of NIRS-Imaging for human brain FORCE: fast-oxygen response in capillary event

Two basic principles to measure positional information using photon have been discovered. The first one is the photon-CT (pCT) technique using straight-line light by Jobsis in 1977. The second is NIRS-Imaging of diffusion/scattering light that was discovered in 1991 by Kato. In the principle of NIRS-Imaging, a position of two probes and temporal responses of a measuring object determines each photon's functional pixels with border unclearness. As NIRS-Imaging uses uncertain light of positional information, it is thought of as a reversal to locate spatial information. At this point, for the pCT, which depends on precision of light for positional information, NIRS-Imaging is a completely opposite principle. It is difficult to penetrate the adult brain with light by pCT. With the discovery of the principle of NIRS-Imaging, which samples photon functional pixels, local blood physiology for oxygen exchange rapidly developed in brain and muscle studies. The sensibility of NIRS-Imaging is high for a signal of active oxygen exchange in capillaries. NIRS-Imaging is a non-invasive measurement for cerebral microcirculation in the capillary, not the vein. It is important to measure fast-oxygen response in capillary event (FORCE) related to neuronal responses, defined as the FORCE effect. Advanced NIRS-Imaging can distinguish the FORCE effect from a watering-the-garden effect. The slow blood change that defined a watering-the-garden effect can induce a strong signal in the vein by PET and fMRI. Therefore, oxygen consumption in tissues using fMRI and PET may be underestimated by the measurement of the passive washout flow in the vein.

Tissue oxygenation and capacity to deliver O 2 do the two go together?

Oxidative phosphorylation is the most important source of energy in mammals. Oxygen capture, convective and diffusive oxygen transport as well as the final intracellular oxygen utilization within the mitochondria represent highly refined mechanisms, supervised by a variety of physiological control systems. Any disease process interfering with the delivery of oxygen to tissue will ultimately lead to an impairment of cellular energy production. Generally, cellular hypoxia may result from either reduced oxygen uptake (hypoxic hypoxia), reduced convective and diffusive oxygen transport (circulatory and anemic hypoxia), impaired oxygen consumption (histotoxic hypoxia), or a combination of these states. To effectively treat any of these conditions, it is mandatory to recognize the underlying specific alterations of oxidative metabolism. Identification of the various types of hypoxia as well as contemporary treatment surveillance strategies depend primarily on measuring oxygen partial pressure in inspiratory gas, blood (arterial, mixed-venous) and tissue (extracellular fluid), next to monitoring of various circulatory parameters. This review focuses (a) on the diagnostic value of different techniques used to monitor blood and tissue oxygenation and (b) on the effects of impaired capacity to deliver O 2 on tissue oxygen delivery and consumption. The potential value of multiparametric monitoring in guiding specific treatment measures to improve oxygen delivery to tissue is highlighted.

Testing the free radical theory of aging in bats.

The extended longevity of bats, despite their high metabolic rates, may provide insight to patterns and mechanisms of aging. I tested the free radical theory of aging as an explanation for the extreme longevity of the little brown bat, Myotis lucifugus (maximum life span potential [MLSP] = 34 years). In a comparative study, I measured whole-organism oxygen consumption and mitochondrial hydrogen peroxide production in brain, heart, and kidney tissues from M. lucifugus and short-tailed shrews, Blarina brevicauda (MLSP = 2 years). As predicted by the free radical theory of aging, M. lucifugus produced approximately half the amount of hydrogen peroxide as B. brevicauda. In addition, I compared oxygen consumption and hydrogen peroxide production of adult (approximately 1 year) and juvenile (fully developed and fledged young of the year) M. lucifugus to assess oxidative damage to mitochondria (measured as an increase in hydrogen peroxide production) due to the high metabolic rate associated with flight. Contrary to my prediction, juveniles had significantly higher levels of hydrogen peroxide production than adults. I propose that the decreased free radical production in adults is the result of within-individual selection of efficient mitochondria due to selective pressure created by the high energetic demands of flight.

Microvascular oxygen transport abnormalities in experimental sepsis interpreted using a computational model

Experimental studies using a peritonitis model of sepsis in rats have reported abnormalities in microvascular perfusion including increased stopped flow capillaries, increased fast flow capillaries and impaired regulation of blood flow. We have used a spectrophotometric functional microvascular imaging system to quantify capillary geometry, red blood cell flow and red blood cell hemoglobin oxygen saturation during sepsis. We found that while oxygen saturation at the entrance of the capillary bed was unaffected in sepsis, there was a significant drop in saturation at the venous end of capillaries with normal velocities. Although the fall in oxygen saturation correlated with the number of stopped flow capillaries, we could not determine from this data whether tissue oxygen consumption changed with sepsis, whether fast flow capillaries acted as functional oxygen shunts or whether any regions of the tissue were anoxic. To address these questions we constructed a computational model that simulated O2 transport in a three-dimensional volume of tissue supplied by heterogeneously spaced capillaries with fast, normal and stopped flow. The model was based on our experimental oxygen transport data (capillary density, number of stopped flow capillaries, capillary red blood cell velocity and supply rate, and entrance oxygen saturation levels) and the model predicted oxygen consumption, tissue oxygen levels and oxygen transport in fast flow capillaries; data that could not be measured experimentally with current technology. Tissue oxygen consumption in the model was adjusted to yield the same venous end oxygen saturation values as measured experimentally. Two cases were modeled; average sepsis (AS) with 33% stopped, 33% normal and 33% fast flow, and extreme sepsis (ES) with 50% stopped, 25% normal and 25% fast flow. Simulations found approximately twofold and fourfold increases in tissue oxygen consumption for AS and ES, respectively. Average (minimum) tissue PO2 decreased from 43(40) mmHg in control to 34 (27) and 26 (15) mmHg in AS and ES, respectively. Clustering fast flow capillaries to increase flow heterogeneity resulted in only a slight decrease in minimum tissue PO2, to 14.5 mmHg. Although fast flow capillaries did appear to be oxygen shunts with higher venous oxygen saturations, they were a significant factor in preventing tissue anoxia during sepsis. Despite the contribution of fast flow capillaries, simulated tissue PO2 values continued to fall as the degree of microvascular injury increased. The model predicts that microvascular oxygen transport abnormalities associated with sepsis expose the tissue to local regions of a hypoxic environment that may lead ultimately to significant changes in cellular function.

Oxidant stress leads to impaired regulation of renal cortical oxygen consumption by nitric oxide in the aging kidney.

Structural and functional changes occur in the kidney with aging. Previous studies have suggested that loss of nitric oxide production contributes to these changes. The authors therefore explored regulation of renal cortical oxygen consumption, a nitric oxide mediated effect, in tissue from Fischer 344 rats at different ages (4, 13, and 23 mo) to characterize changes in renal nitric oxide production with age. Bradykinin, enalaprilat, and amlodipine significantly suppressed cortical oxygen consumption in 4-mo-old rats (bradykinin: -2.5 +/- 0.9% to -21 +/- 1.5%; enalaprilat: -0.7 +/- 0.5% to -26 +/- 1.2%; amlodipine: -1.3 +/- 0.9% to -18 +/- 1.2%; P < 0.05). Similar results were obtained in 13-mo-old animals. However, in 23-mo-old animals, the responses to bradykinin and enalaprilat were attenuated (bradykinin: 0 +/- 0% to -13 +/- 0.9%; enalaprilat: -0.3 +/- 0.3% to -17 +/- 2.1%; P < 0.05), whereas the response to an NO donor was unaffected, suggesting decreased bioavailability of NO. Addition of the superoxide radical scavenger tempol restored the ability of bradykinin, enalaprilat, and amlodipine to suppress oxygen consumption in tissue from 23-mo-old animals to levels seen in younger animals, suggesting NO destruction by superoxide as the reason for decreased NO availability. Apocynin, an inhibitor of NAD(P)H oxidase, similarly restored the ability of all three drugs to suppress oxygen consumption, suggesting NAD(P)H oxidase as the enzyme responsible for enhanced superoxide production in aging. Levels of eNOS protein, assessed by immunoblotting, did not change significantly with age. These results suggest that NO availability is decreased in the aging kidney and that this is due to scavenging of NO by superoxide produced by NAD(P)H oxidase. Oxidant stress, by depleting NO, may contribute to the structural and hemodynamic changes characteristic of the aging kidney.

Effect of live weight gain of steers during winter grazing: II. Visceral organ mass, cellularity, and oxygen consumption.

Two experiments were conducted to examine the effect of BW gain during winter grazing on mass, cellularity, and oxygen consumption of splanchnic tissues before and after the feedlot finishing phase. In each experiment, 48 fall-weaned Angus x Angus-Hereford steer calves were assigned randomly to one of three treatments: 1) high rate of BW gain grazing winter wheat (HGW), 2) low rate of BW gain grazing winter wheat (LGW), or 3) grazing dormant tallgrass native range supplemented with 0.91 kg/d of a 41% CP supplement (NR). At the end of winter grazing, four steers were selected randomly from each treatment for initial slaughter to measure organ mass, cellularity, and oxygen consumption. All remaining steers were placed into a feedlot and fed to the same backfat end point (1.27 cm). Six steers were selected randomly from each treatment for final organ mass, cellularity, and oxygen consumption. Initial empty BW (EBW) was greatest (P < 0.001) for HGW, intermediate for LGW, and least for NR steers in both Exp. 1 and 2 (355 > 263 > 207 +/- 6.5 kg and 337 > 274 > 205 +/- 8.7 kg, respectively). For both experiments, the initial total gastrointestinal tract (GIT; g/kg of EBW) proportional weight was greater (P < 0.05) in NR steers than in LGW, and LGW steers had greater (P < 0.05) initial GIT proportional weight than HGW steers. Proportional weight of total splanchnic tissues (TST; g/kg of EBW) did not differ (P < 0.19) among treatments. Initial duodenal RNA concentration and RNA:protein were greater (P < 0.02) in LGW than in HGW steers, and NR steers were intermediate. Initial in vitro liver O2 consumption was greater (P < 0.09) in HGW and LGW than in NR steers (34.5 > 16.9 mL/min), whereas initial small intestinal oxygen consumption was greater (P < 0.01) in LGW than in HGW and NR steers (12.1 > 5.2 mL/min). Ruminal papillae oxygen consumption did not differ (P < 0.55) among treatments. The rate of decrease of GIT (g x g EBW(-1) x d(-1)) during finishing was greater in NR than in HGW and LGW steers in both Exp. 1 and 2, but mesenteric fat (g x g EBW(-1) x d(-1)) increased for NR steers, resulting in a similar (P < 0.75) increase in TST across the finishing period for all treatments. Similar rates of increase in TST across the finishing phase corresponded with similar rates of live and carcass weight gain among treatments. Our data support the hypothesis that increased visceral organ mass increases maintenance energy requirements of growing cattle.

The relationship between central venous saturation and outcome following high-risk surgery

Central venous oxygen saturation (ScvO2) reflects both tissue oxygen delivery and consumption and has been shown experimentally to closely reflect a range of circulatory disturbances. This and related parameters have been used successfully to improve outcome in various patient groups. Despite this fact, there is little or no observational data to link derangements of these parameters to outcome in the high-risk surgical patient.

Coronary microvascular endothelial stunning after acute pressure overload in the conscious dog is caused by oxidant processes: the role of angiotensin II type 1 receptor and NAD(P)H oxidase.

Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation. In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin. Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.

Pharmacology Review

During the past 2 decades, dopamine has become the most frequently used sympathomimetic amine in the treatment of neonatal shock. The observations that severe and prolonged hypotension may result in the development of irreversible shock, which is associated with increased mortality and central nervous system morbidity, form the rationale behind the early use of dopamine and other sympathomimetic amines in neonates if volume administration fails. However, although cautious volume administration and the early use of dopamine are effective in improving the cardiovascular status and renal function in most neonates who have hypotension, there is only indirect evidence that the use of dopamine (and the other sympathomimetic amines) in the management of neonatal shock improves mortality and morbidity. Recent advances in understanding of the pathophysiology of neonatal shock and the developmentally regulated mechanisms of dopamine action have led to more sophisticated use of this drug. Yet, limitations in the ability to assess accurately tissue perfusion at the bedside present challenges to management of neonatal shock, especially in the very preterm neonate during the immediate postnatal period. Furthermore, although recent studies have shed light on the effects of dopamine on regional organ blood flow in the neonate, there is very little evidence on the effects of dopamine (and the other sympathomimetic amines) on tissue oxygen delivery and consumption. Bearing these limitations in mind, we review the mechanisms of action and pharmacokinetics of dopamine and discuss the cardiovascular, renal, and neuroendocrine effects of the drug. Additionally, we examine the clinical evidence supporting and challenging the use of this sympathomimetic amine in the treatment of neonatal cardiovascular compromise. Dopamine, an endogenous catecholamine and the precursor of epinephrine and norepinephrine, plays an important physiologic role in the regulation of cardiovascular, renal, neuroendocrine, and central nervous system functions. Therefore, when used for its cardiovascular and renal …

Switching of metabolic-rate scaling between allometry and isometry in colonial ascidians.

The metabolic rate and its scaling relationship to colony size were studied in the colonial ascidian Botrylloides simodensis. The colonial metabolic rate, measured by the oxygen consumption rate (V(O2) in millilitres of O(2) per hour) and the colony mass (wet weight M(w) in grams) showed the allometric relationship (V(O2) = 0.0412 M(w)(0.799). The power coefficient was statistically not different from 0.75, the value for unitary organisms. The size of the zooids and the tunic volume fraction in a colony were kept constant irrespective of the colonial size. These results, together with the two-dimensional colonial shape, excluded shape factors and colonial composition as possible causes of allometry. Botryllid ascidians show a takeover state in which all the zooids of the parent generation in a colony degenerate and zooids of a new generation develop in unison. The media for connection between zooids such as a common drainage system and connecting vessels to the common vascular system experienced reconstruction. The metabolic rate during the takeover state was halved and was directly proportional to the colonial mass. The scaling thus changed from being allometric to isometric. The alteration in the scaling that was associated with the loss of the connection between the zooids strongly support the hypothesis that the allometry was derived from mutual interaction among the zooids. The applicability of this hypothesis to unitary organisms is discussed.

Oxygen regulation and limitation to cellular respiration in mouse skeletal muscle in vivo

In skeletal muscle, intracellular Po2 can fall to as low as 2-3 mmHg. This study tested whether oxygen regulates cellular respiration in this range of oxygen tensions through direct coupling between phosphorylation potential and intracellular Po2. Oxygen may also behave as a simple substrate in cellular respiration that is near saturating levels over most of the physiological range. A novel optical spectroscopic method was used to measure tissue oxygen consumption (Mo2) and intracellular Po2 using the decline in hemoglobin and myoglobin saturation in the ischemic hindlimb muscle of Swiss-Webster mice. 31P magnetic resonance spectroscopic determinations yielded phosphocreatine concentration ([PCr]) and pH in the same muscle volume. Intracellular Po2 fell to <2 mmHg during the ischemic period without a change in the muscle [PCr] or pH. The constant phosphorylation state despite the decline in intracellular Po2 rejects the hypothesis that direct coupling between these two variables results in a regulatory role for oxygen in cellular respiration. A second set of experiments tested the relationship between intracellular Po2 and Mo2. In vivo Mo2 in mouse skeletal muscle was increased by systemic treatment with 2 and 4 mg/kg body wt 2,4-dinitrophenol to partially uncouple mitochondria. Mo2 was not dependent on intracellular Po2 above 3 mmHg in the three groups despite a threefold increase in Mo2. These results indicate that Mo2 and the phosphorylation state of the cell are independent of intracellular Po2 throughout the physiological range of oxygen tensions. Therefore, we reject a regulatory role for oxygen in cellular respiration and conclude that oxygen acts as a simple substrate for respiration under physiological conditions.

Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats.

Traumatic brain injury (TBI) triggers a complex pathophysiological cascade, leading to cell death. A major factor in the pathogenesis of TBI is neuronal overloading with calcium, causing the opening of mitochondrial permeability transition pores (MPTP), which consequently inhibit normal mitochondrial function. The immunosuppressant Cyclosporin A (CsA) has been shown to block MPTPs, and to be neuroprotective in ischemia and TBI. However, the translation of these effects on mitochondrial function, into behavioral endpoints has not been investigated thoroughly. Therefore, we tested the effect of a low, clinically evaluated, CsA dose of 0.125 mg/kg (infused for 3 h) and a higher "known" neuroprotective dose of 18.75 mg/kg on brain tissue O(2) consumption, and on motor and cognitive performance following lateral fluid percussion injury (FPI) in rats. CsA at both concentrations abolished the 25% decrease in O(2) consumption (VO(2)), seen in saline-treated animals at 5 h post-FPI. Furthermore, the lower dose of CsA also ameliorated acute motor deficits (days 1-5 post-FPI) and learning and memory impairments in a Morris water maze test on days 11-15 post-FPI. Although, the higher dose of CsA improved cognitive performance, it worsened acute motor functional recovery. These results suggest, that the CsA-induced preservation of mitochondrial function, as assessed by tissue O(2) consumption, directly translated into improvements in motor and cognitive behavior.

Influence of high contents of dietary soybean oil on growth, feed utilization, tissue fatty acid composition, heart histology and standard oxygen consumption of Atlantic salmon ( Salmo salar) raised at two temperatures

The uncertain supply and variable price of fish oil warrants the investigation of other sources of energy in salmon diets. A study was done to test the effects on growth, feed utilization, tissue fatty acid composition, heart histology and standard oxygen consumption of replacing 50% or 100% of the supplementary fish oil (FO) with soybean oil (SO) in high energy, fish meal-based diets for Atlantic salmon smolts. Triplicate groups of fish were tested for approximately 950 day-degrees (DD) at both 5 (initial weight, 108 g) and 12 °C (initial weight, 118 g). The salmon tripled their weight during the trial. Total feed intake and growth were significantly greater in the groups fed the 100% FO diet compared with those fed the 50% SO diet, with the 100% SO-fed groups in the middle. Feed efficiency ratios were not affected by dietary treatment or water temperature. No histological pathologies were found in heart tissue of salmon sampled at the end of the trial. Neither diet nor temperature affected whole body composition or lipid content in the heart of fish sampled at the end of the trial. Standard oxygen consumption was significantly lower in salmon fed the 50% SO diet (83±2 mg O 2 kg −1 h −1) compared with fish fed the 100% FO and 100% SO diets (90±2 and 92±2 mg O 2 kg −1 h −1, respectively). In general, the levels of the individual fatty acids in the triacylglyerol fraction of the heart and fillet lipids showed either no response or a linear response to the corresponding fatty acids in the diets. Thus, no relationship was evident between the tissue fatty acid levels and oxygen consumption. This study showed that Atlantic salmon grow well and with high efficiency on high energy, fish meal-based diets containing up to 100% supplementary soybean oil. No evidence of detrimental effects of the soybean oil on the health of the fish was found.

Olive oil feeding up-regulates uncoupling protein genes in rat brown adipose tissue and skeletal muscle

Some nutrients, such as carotenoids, retinoic acid, and certain types of fatty acids, increase thermogenic capacity. The influence of 4 dietary lipid sources (olive oil, sunflower oil, palm oil, and beef tallow) on the content of uncoupling proteins 1, 2, and 3 (UCP1, UCP2, and UCP3) and their messenger RNA (mRNA) expression in several tissues of rats was compared. Wistar rats were randomly divided into 4 groups and fed ad libitum diets containing 40% of energy as fat. UCP1, UCP2, and UCP3 mRNA and protein were assessed by Northern blot and Western blot, respectively. Oxygen consumption in tissues was measured by polarography. Total-body oxygen consumption was assessed in an open-circuit chamber system. Circulating fuels (fatty acids and glucose) and hormones (triiodothyronine, thyroxine, corticosterone, and insulin) were measured. Olive oil feeding induced the highest UCP1, UCP2, and UCP3 mRNA expression in interscapular brown adipose tissue. An analogous effect was observed in gastrocnemius muscle UCP3 mRNA. No significant differences were observed in perirenal white adipose tissue UCP2 mRNA. Changes in mRNAs were not accompanied by close changes in the protein content of UCPs and were not associated with changes in adipose tissue oxygen consumption. Nevertheless, total-body oxygen consumption was higher in rats fed olive oil than in those fed the other 3 diets. No significant differences were found in body and tissue weights or in serum indexes. Olive oil induced an up-regulating effect on UCP mRNA that was probably not mediated by systemic metabolic changes, but rather related to a local effect on interscapular brown adipose tissue and skeletal muscle.

Paradoxical release of nitric oxide by an L-type calcium channel antagonist, the R+ enantiomer of amlodipine.

Amlodipine is a mixture of two enantiomers, one having L-type channel blocking activity (S-) and the other about 1,000-fold weaker activity and of little known other activity (R+). To determine whether the R+ enantiomer releases nitric oxide, the ability of amlodipine, its enantiomers, and nitrendipine to release nitric oxide in isolated coronary microvessels and to regulate cardiac tissue oxygen consumption via nitric oxide release was studied in vitro. Amlodipine and the R+ enantiomer released nitric oxide in a concentration-dependent fashion, increasing nitrite release from coronary microvessels by 57 +/- 12 and 45 +/- 5 pmol/mg/20 min at 10(-6) M (p < 0.05 from control). Nitrite release was entirely blocked by N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and HOE-140, a B2-kinin receptor antagonist. The S- enantiomer had no effect on nitrite release at any concentration. Amlodipine and the R+ enantiomer also reduced oxygen consumption in canine cardiac tissue in vitro and this was in an L-NAME-blockable manner. The S- enantiomer of amlodipine had no effect. This study shows that the R+ enantiomer of amlodipine is responsible for the release of nitric oxide and not the S- enantiomer (the L-type calcium channel blocking portion of amlodipine). Interestingly, nitric oxide release is dependent on the production of kinins because it is blocked by HOE-140. This study defines a potentially important property by which calcium channel blockers may release nitric oxide and may contribute to their use in the treatment of cardiovascular disease.

Messung der regionalen zerebralen Sauerstoffsättigung (rSO 2 ) mit near-infrared-Spektroskopie bei Kindern während postoperativer Hyperventilations- und Hyperoxygenierungsphasen

We report about the determination of the regional cerebral oxygen saturation of 30 children without any cerebral diseases. The regional cerebral oxygen saturation is not used routinely to describe the oxygenation of the infant brain. Methods and patients: We used the near-infrared-spectroscopy equipment by Symanetics (USA). We examined prospectively the correlation between hyperoxygenation, hypercapnia and regional cerebral saturation in 30 children with artificial respiration after a cardiac operation. Results: We found an decreased regional cerebral saturation from 68.6% to 65.5% in children with hypercapnia. The regional cerebral saturation increased from 65.9% to 69.1% during the time of hyperoxygenation (100% O 2 ). Conclusions: The interpretation of the regional cerebral saturation is difficult, because there is a multifactorial influence on this. That is why this method is not used routinely. The following points influence the regional cerebral saturation: the distribution of the intracerebral blood pool, the oxygenation of the blood, the cerebral blood flow, and the oxygen consumption of the cerebral tissue. We found a significant correlation between an increasing of the regional cerebral saturation and a small increasing of CO 2 .

Attenuation of vascular endothelial dysfunction by testosterone receptor blockade after trauma and hemorrhagic shock.

The salutary effects of the testosterone receptor antagonist flutamide on the depressed immune and cardiovascular functions after hemorrhage and resuscitation are related to improved endothelial cell function, which can subsequently lead to an increase in organ blood flow, oxygen delivery, and tissue oxygen consumption. Male adult rats underwent a 5-cm midline laparotomy (ie, trauma) and were bled to and maintained at a mean systemic arterial pressure of 40 mm Hg until 40% maximal blood-out volume was returned in the form of Ringer lactate). The animals were then resuscitated with 4 times the total volume of shed blood with Ringer lactate for 60 minutes. Flutamide (25 mg/kg) or an equivalent volume of the vehicle propanediol was injected subcutaneously 15 minutes before the end of resuscitation. At 20 hours after resuscitation, aortic rings (approximately 2.5 mm in length) were isolated and mounted in an organ chamber. Dose responses for an endothelium-dependent vasodilator (acetylcholine chloride) and endothelium-independent vasodilator (nitroglycerine) were determined. Organ blood flow was measured using strontium 85-labeled microspheres. Total hemoglobin and oxygen content in the femoral artery and portal, hepatic, and renal veins were determined. Oxygen delivery and consumption in liver, small intestine, and kidneys were calculated. Administration of flutamide after trauma-hemorrhage attenuated the depressed endothelial function. Furthermore, flutamide treatment restored the reduced blood flow and oxygen delivery and consumption in all organs tested after trauma-hemorrhage and resuscitation. Flutamide appears to be a useful adjunct for improving vascular endothelial function and regional hemodynamics after trauma-hemorrhage and resuscitation.