Evidence of myocardial injury during prolonged strenuous exercise

These preliminary data suggest that extremely prolonged intense exercise may induce subclinical myocardial injury. Although questions of assay interference exist, the importance of this finding has prompted planning of a larger study using a methodologically more specific assay.     

Effect of propionic acid on fatty acid oxidation and ureagenesis

Propionic acid significantly inhibited 14CO2 production from [1-14C] palmitate at a concentration of 10 muM in control fibroblasts and 100 muM in methylmalonic fibroblasts. This inhibition was similar to that produced by 4-pentenoic acid. Methylmalonic acid also inhibited 14CO2 production from [1-14C] palmitate, but only at a concentration of 1 mM in control cells and 5 mM in methylmalonic cells. Propionic acid (5 mM) also inhibited ureagenesis in rat liver slices when ammonia was the substrate but not with aspartate and citrulline as substrates. Propionic acid had no direct effect on either carbamyl phosphate synthetase or ornithine transcarbamylase. These findings may explain the fatty degeneration of the liver and the hyperammonemia in propionic and methylmalonic acidemia.     

Immune parameters in athletes before and after strenuous exercise

Secretory IgA levels were studied in nationally ranked Nordic skiers before and after the national cross-country races held in February 1981. Comparing the skiers with age-matched controls, there was significantly lower level of salivary IgA before the race. Concentrations of IgA decreased further following the competition (50 kn for males; 20 km for females) to very low levels. There also were a significant increase in the percentage of B lymphocytes and a decrease in the null population (non-T, non-B) in the athletes after the race compared with the controls. The mechanism responsible for these changes is unknown, but the low salivary IgA levels may result from depletion of nasal fluid and/or malfunction of the mucosal plasma cells due to a decrease temperature in the mucous membranes. We speculated that a temporary antibody deficiency on the mucosal surface might lead to a susceptibility to acquiring viral and bacterial infections, especially during the interval immediately following strenuous exercise.     

Peroxisomal fatty acid oxidation capacity is more resistant to ischaemic and reperfusion injury than mitochondrial fatty acid oxidation capacity in feline hearts

Mitotic recombination induced by six alkylating agents has been studied in the wing-spot test of Drosophila melanogaster. The model mutagens chosen have different models of action at the DNA level. These are: the direct-acting small alkylating agent methylmethanesulfonate (MMS), the small promutagens N-dimethylnitrosamine (DMN) and N-diethylnitrosamine (DEN), the bifunctional cross-linking alkylating agents mitomycin C (MMC), chlorambucil (CLA) and monocrotaline (MCT). Flies of the standard cross (flr3 / TM3, Bds females and mwh males) were used to produce the larvae to be treated. Three-day old Drosophila larvae were exposed by chronic feeding for 48 h to three different concentrations of all six alkylating agents. Acute feeding for only 2 h was used in addition with DEN and MMC. Wings of the marker-heterozygous (mwh+ / + flr3) as well as of the balancer-heterozygous (mwh+ / TM3, Bds) progeny were analysed. The ranking of the compounds with respect to their genotoxic potency, based on mwh clone formation frequency in marker-heterozygous wings was: MMS > MNC > DMN > CLA approximately MCT > DEN. The ranking with respect to the induction of twin spots, which are produced by mitotic recombination exclusively, was: MMS > DMN > MMC > MCT > CLA > DEN. The quantitative determination of recombinagenic activity, based on mwh clone formation frequencies obtained in both types of wings, gave the following values: MMS, 93%; MCT, 87%; CLA, 80%; MMC, 73%; DMN, 67%; DEN, 22%. A clear relationship exists between the extent of N-alkylation of DNA and the efficiency of the monofunctional agents MMS and DMN as well of the bifunctional agents MCT, CLA and MMC to induce mitotic recombination. This contrasts with the ethylation of base oxygen atoms and the resulting lower efficiency of DEN to produce mitotic recombination.     

Regulation of tumour cell fatty acid oxidation by n-6 polyunsaturated fatty acids

The aim of this study was to evaluate acute effects of ethyl tert-butyl ether (ETBE) in man after short-term exposure. ETBE may in the future replace methyl tert-butyl ether, a widely used oxygenate in unleaded gasoline. Eight healthy male volunteers were exposed to ETBE vapor for 2 h at four levels (0, 5, 25, and 50 ppm) during light physical exercise. The subjects rated irritative symptoms, discomfort, and central nervous system effects in a questionnaire. Ocular (eye redness, tear film break-up time, conjunctival epithelial damage, and blinking frequency), nasal (acoustic rhinometry and analysis of inflammatory markers and cells in nasal lavage fluid), and pulmonary (peak expiratory flow, forced expiratory volume in 1 s, forced vital capacity, vital capacity, and transfer factor) measurements were performed. Significantly increased ratings of solvent smell (p = 0.001, repeated-measures ANOVA) were seen during exposures and correlated to exposure levels. Furthermore, significantly elevated ratings of discomfort in throat and airways were seen during and after 50 ppm compared to the control exposure (p = 0.02). Increased nasal swelling (p = 0.001) and blinking frequency (p = 0.01) were noted at all exposure levels, but their magnitudes were not related to exposure levels. A slightly impaired pulmonary function was seen at 25 and 50 ppm, since forced vital capacity (p = 0.02) and vital capacity (p = 0.04) differed significantly from the clean air exposure. Although the impairments seemed to fall within normal inter- and intraindividual variation and have no clinical relevance as such, it cannot be excluded that other individuals may react more severely than eight healthy male volunteers in this study.     

Modulation of peroxisomal and microsomal fatty acid oxidation by acetone. A comparative study between liver and kidney

Using an immunoelectron microscopic technique, we demonstrated the distinctive localization of L-selectin, alphaL and beta2 integrins (LFA-1) on lymphocytes adhering to high endothelial venules (HEVs) of peripheral lymph nodes. Immunogold staining clearly demonstrated the preferential localization of L-selectin on the faintly adherent microvilli to endothelial surfaces. Often, the particles of L-selectin were found around those microvilli with a dispersed distribution. Examination by antibody-coated latex beads showed that the localization of L-selectin was not restricted to the lymphocyte surface but also found on endothelial cells. These data suggest the molecular shedding from lymphocytes and its transfer to the HEV surface as the 'molecular footprints' of rolling cells. Concomitant with the dispersion of L-selectin, the gold particles of alphaL, and beta2 integrins showed significant capping and clustering images on the adherent border of lymphocytes. This redistribution of LFA-1 may be important for inducing the transition of the molecule into the active state to facilitate effective binding to its endothelial ligands. These morphological findings revealed the characteristic behavior of L-selectin and LFA-1 on lymphocytes, and they confirm their respective molecular roles in the current adhesion cascade model between lymphocytes and HEVs.     

Impaired fatty acid oxidation in children on valproic acid and the effect of L-carnitine

Fatty acid oxidation was studied in 12 patients (aged 3 to 19 years) receiving valproic acid (VPA), predominantly as monotherapy, before and after 1 month of L-carnitine supplementation (50 mg/kg/day po) in order to determine whether L-carnitine plays a role in preventing the hepatotoxic effects of this drug. Five of these patients were also studied prior to VPA treatment. Only one patient taking VPA had an abnormally low plasma free carnitine. Acyl-/free carnitine ratios were elevated in five patients on VPA and normalized after L-carnitine supplementation. Mean plasma concentrations of free fatty acids, beta-OH-butyrate, and cumulative excretion of 13CO2 after administration of 1-13C-octanoic acid were not changed by VPA or L-carnitine treatment. Urinary dicarboxylic acids, acylglycines, and octanoylcarnitine were elevated during VPA therapy and unaltered by L-carnitine. These results suggest that, in patients at low risk for VPA-induced hepatotoxicity (patients aged > 2 years and taking VPA as monotherapy), VPA causes metabolic abnormalities resembling those found in inborn errors of mitochondrial beta-oxidation which are not corrected by L-carnitine.     

Alterations in eighteen-carbon saturated, monounsaturated and polyunsaturated fatty acid peroxisomal oxidation in mouse brain during development and aging

PURPOSE/OBJECTIVES: To provide an update on the breast cancer genes BRCA1 and BRCA2 and to review available primary preventive options. DATA SOURCES: Published articles, abstracts, and clinical experience. DATA SYNTHESIS: While genetic testing will help identify a cadre of women at high risk for breast cancer development, it also will raise many psychosocial and ethical issues, including if and when to be tested and what patients and healthcare professional should do with the information. CONCLUSIONS: The only currently available putative form of primary prevention is prophylactic mastectomy. Diet and the use of tamoxifen remain areas for future research. IMPLICATIONS FOR NURSING PRACTICE: Nurses can play an important role in educating patients who face difficult decisions surrounding genetic testing and primary prevention modalities. Nurses also can design and conduct much needed research in these areas.     

Ventilatory and arterial blood gas tension adjustments to strenuous exercise in standardbreds

Five healthy, fit Standardbreds (mean +/- SEM, 490.4 +/- 15.0 kg, 4.0 +/- 0.5 years) were studied during a standardized test carried out on a treadmill. The test consisted of an 8-minute warm-up and a 9-minute exercise period (1 minute at 1.7, 4, 7, 8, 9, and 10 m/s; 2 minutes at 4 m/s; and a 1-minute walk at a 6% slope). Respiratory airflow, tidal volume (V(T)), and respiratory frequency (f) were continuously recorded, using 2 ultrasonic pneumotachographs connected to a face mask and mass spectrometer. Oxygen uptake, carbon dioxide output, and expired minute volume (V(E)) were obtained on a breath by breath basis. Arterial blood was tested at the end of each step for O2 and CO2 partial pressures. Heart rate was continuously recorded, using a heart rate recording system. Stride frequency was measured at each step, and the stride frequency-to-f ratio was calculated. Venous blood was tested for plasma lactate concentration be fore and 2 minutes after completion of the test. Some horses had a locomotion-respiration coupling (LRC), but this coupling was occasional and intermittent. The f was lower and V(T) was higher than values reported for thoroughbreds working under similar experimental conditions. Nevertheless, maximal V(E) did not overshoot maximal V(E) reported in Thoroughbreds. All horses were hypoxemic and hypercapnic, but there was wide variability between subjects. The horses with the highest oxygen uptake and the lowest plasma lactate concentration were more hypoxemic and hypercapnic. The Standardbreds, studied under our laboratory conditions, did not have constant LRC and had lower f with higher V(T) than did Thoroughbreds under similar experimental conditions. Despite these differences in breathing strategy, the Standardbreds did not have higher V(E) than did Thoroughbreds, and they were hypoxemic and hypercapnic. The fact that these Standardbreds, which obviously freely selected their breathing strategy, were unable or unwilling to adopt compensatory hyperventilation reinforces the hypothesis that, in strenuous exercising horses, there could be a physiologic limit to ventilation, most probably related to mechanical factors, but independent of any LRC.     

Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes

We have studied the inhibitory action of long- and short-chain fatty acids on hepatic glucose utilization in hepatocytes isolated from fasted rats. The rates of hepatic glucose phosphorylation and glycolysis were determined from the tritiated products of [2-3H] and [6-3H]glucose metabolism, respectively. The difference between these was taken as an estimate of the 'cycling' between glucose and glucose-6-phosphate. In the presence of 40 mM glucose this cycling was estimated at 0.68 mumol/min/g wet wt. Glucose phosphorylation was unaffected during palmitate and hexanoate oxidation to ketone bodies but glycolysis was inhibited. The rate of glucose cycling was increased during this phase to 1.25 mumol/min/g. Following the complete metabolism of the fatty acids, glycolysis was reinstated and cycling rates returned to control levels. Hepatic glucose cycling appears to be an important component of the glucose/fatty acid cycle.     

Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation

We have studied mechanisms by which leptin overexpression, which reduces body weight via anorexic and thermogenic actions, induces triglyceride depletion in adipocytes and nonadipocytes. Here we show that leptin alters in pancreatic islets the mRNA of the genes encoding enzymes of free fatty acid metabolism and uncoupling protein-2 (UCP-2). In animals infused with a recombinant adenovirus containing the leptin cDNA, the levels of mRNAs encoding enzymes of mitochondrial and peroxisomal oxidation rose 2- to 3-fold, whereas mRNA encoding an enzyme of esterification declined in islets from hyperleptinemic rats. Islet UCP-2 mRNA rose 6-fold. All in vivo changes occurred in vitro in normal islets cultured with recombinant leptin, indicating direct extraneural effects. Leptin overexpression increased UCP-2 mRNA by more than 10-fold in epididymal, retroperitoneal, and subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese rats. By directly regulating the expression of enzymes of free fatty acid metabolism and of UCP-2, leptin controls intracellular triglyceride content of certain nonadipocytes, as well as adipocytes.     

Relationship between adherence to exercise and scores on extraversion and neuroticism

A sample of 116 subjects were classified as adherers or drop-outs on the basis of exercising at an on-campus exercise facility over 1 yr. Scores on the Eysenck Personality Inventory showed that adherers did not differ from drop-outs in scores on extraversion; however, drop-outs recorded significantly higher neuroticism scores than adherers.     

Inhibiting effects of mixtures of alpha-tocopherol with beta-carotene or vitamin A during oxidation of polyunsaturated fatty acid esters]

Use of sodium sulfite to reduce nitrogenous contamination in fiber analysis was evaluated. The effects of sodium sulfite on analytical accuracy and precision were examined for amylase-treated neutral detergent fiber (aNDF), sequentially determined acid detergent fiber (sADF), and acid detergent lignin (sADL) in animal feeds. In one experiment, 0.5 g sodium sulfite was added per sample during neutral detergent (ND) extraction. The treatment consistently reduced aNDF, sADF, and sADL values of 180 alfalfa samples and improved precision (decreased within-sample variance of replicated analyses). The greatest effect was on precision of sADL analysis, with within-sample variance reduced by more than 50%. In a second experiment, 24 animal feeds were analyzed for a aNDF, sADF, and sADL with and without addition of 0.5 g sodium sulfite per sample during ND extraction. Nitrogen contents of the recovered fiber fractions were determined. Sodium sulfite reduced fiber and lignin values and decreased nitrogen concentration in residues. Within-sample variance was lower in all analyses. In a third experiment, 23 animal feeds were analyzed for aNDF with sodium sulfite at 0, 0.25, 0.5, and 1.0 g per sample. Average aNDF of feeds was reduced by each additional increment of sodium sulfite; however, 1.0 g sodium sulfite resulted in only a slight reduction in aNDF compared with 0.5 g. Therefore, 0.5 g sodium sulfite per sample should be added to samples prior to aNDF analysis.     

Primary plasmalemmal carnitine transporter defect manifested with dicarboxylic aciduria and impaired fatty acid oxidation

Respiratory syncytial virus (RSV), a common cause of both upper and lower respiratory tract infection (LRTI) in infants and children, is rarely described as an infective agent in adults. It has been reported in bone marrow transplant (BMT) recipients and patients with malignancy immunosuppressed by chemotherapy. Such reports are often associated with a high mortality. We report an outbreak of RSV infection which occurred predominantly in BMT recipients in which early investigation and institution of ribavirin therapy resulted in all patients making a full recovery.     

Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.     

Heat stress induces rapid recovery of mechanical function of ischemic fatty acid perfused hearts by stimulating glucose oxidation during reperfusion

Whole-body heat stress (HS) in rats leads to the accumulation of myocardial heat shock proteins and subsequent protection against ischemic injury in glucose-perfused hearts. We determined whether HS treatment would confer protection against ischemia in hearts perfused with high levels of fatty acids. In addition, since fatty acids can potentiate ischemic injury by inhibiting glucose metabolism, the effects of HS on glucose utilization were also determined. Anesthetized rats were subjected to whole-body hyperthermia by raising body temperature to 41-42 degrees C 15 min. Twenty four hours later, their hearts were perfused with buffer containing either 11 mM glucose alone or 11 mM glucose and 1.2 mM palmitate, and then subjected to ischemic conditions followed by reperfusion. In hearts perfused with glucose only, HS improved aortic flow (expressed as percent change from preischemic aortic flow) late into the reperfusion period. Rates of overall glucose utilization under these conditions were similar between control and HS hearts. When hearts were perfused with 1.2 mM palmitate, the benefits of HS on aortic flow occurred at the onset of the reperfusion period. This beneficial effect was associated with a significant increase in glucose oxidation. Our results show that HS induces a faster rate of recovery in fatty acid perfused hearts but does not offer more protection against ischemic damage when compared with hearts perfused with glucose as a sole substrate.     

Associations between breathing pattern during submaximal exercise and exercise capacity in patients with pulmonary emphysema

We sought to clarify the factors associated with exercise capacity in patients with pulmonary emphysema. Exercise capacities of 20 men with pulmonary emphysema were evaluated by bicycle ergometery, and the results were used to divide the subjects into two groups: high exercise capacity (n = 10) and low exercise capacity (n = 10). Pulmonary-function tests were done, emphysema scores were computed from CT scans, breathing pattern was recorded during submaximal exercise (up to 20 watts), and index of rapid shallow breathing was computed. Neither FEV1 nor airway resistance differed between the two groups, and patients with lower exercise capacity tended to have lower tidal volumes and higher values of the index of rapid shallow breathing during submaximal exercise. Functional residual capacity measured by body plethysmography and emphysema scores were inversely associated with exercise capacity. We speculate that among patients with pulmonary emphysema and a given degree of airway obstruction, a high functional residual capacity causes breathing during submaxinal exercise to be rapid and shallow, and that this rapid and shallow breathing makes ventilation inefficient, increases the work of breathing, and limits exercise capacity.     

Relationship between external resistances, lung function changes and maximal exercise capacity

In upper airway obstruction (UAO) the relationship between the degree of obstruction, exercise limitation and lung function indices is not well established. Therefore, we investigated in nine healthy subjects (age 36+/-9 yrs) the effects of two added resistances at the mouth (R1 = added resistance with 7.8 mm diameter; R2 = 5.7 mm) on forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), airway resistance (Raw) and maximal breathing capacity (measured during 15 s = measured maximum breathing capacity (MBCm); calculated as FEV1x37.5 = calculated maximum breathing capacity (MBCc)) on the one hand, and maximum exercise capacity (W'max), minute ventilation (V'E) and CO2 elimination (V'CO2) on the other. We found that R1 had almost no influence on FEV1 but decreased PEF by approximately 35% and increased Raw by almost 300%; it decreased W'max by merely approximately 10% while maximal exercise ventilation (V'Emax) was only 65% of control and only reached approximately 40% MBCc and approximately 70% MBCm; yet V'E and V'CO2 were significantly reduced at high exercise levels indicating hypoventilation. With R2, FEV1 was reduced by 25% and PEF by 55%, and Raw was increased by 600%; W'max was approximately 60% of control, V'Emax was only 35% of control and reached approximately 30% MBCc and approximately 60% MBCm, V'E was already reduced at moderate exercise levels. We conclude that: 1) an upper airway obstruction of 6 mm diameter (but not of 8 mm) had a marked influence on maximum exercise capacity due to hypoventilation; 2) calculated maximum breathing capacity markedly overestimated measured maximum breathing capacity because the forced expiratory volume in one second is an insensitive index of upper airway obstruction and because it does not take inspiratory flow limitation into account; and 3) a 10% decrease in maximum exercise capacity was linearly related with a 7% decrease in the forced expiratory volume in one second and a 150% increase in airway resistance. A 10% decrease in maximal exercise ventilation was related to a 8.5% decrease in peak expiratory flow and 9% decrease in measured maximum breathing capacity.