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J K Barclay

Publications and source records attributed to J K Barclay.

At least 55 records · Page 3Linked to original sources

Hyperoxia, mitochondrial redox state, and lactate metabolism of in situ canine muscle.

The effect of hyperoxia on lactate production and release and the mitochondrial NAD+-to-NADH ratio was studied in the in situ canine gastrocnemius to determine whether elevated PO2 altered metabolic regulation. Dogs breathed either air (21% O2) [arterial O2 partial pressure (PaO2) 90 mmHg; n = 8] or hyperoxia (100% O2) (PaO2 546 mmHg; n = 8). The left muscle was stimulated for 10 min at 3 Hz and then both right and left muscles were quick frozen in N2. Hyperoxia did not affect O2 uptake, blood flow, and developed tension. Activity increased glucose 6-phosphate (G-6-P), D-fructose 6-phosphate (F-6-P), NH3, lactate, and F-6-P/F-1,6-P in both treatment groups. No significant differences in arterial or venous lactate, muscle lactate, glucose uptake, or glycogen depletion were noted in hyperoxia. Cytoplasmic NAD+/NADH was in a more oxidized state in hyperoxia at rest but not during activity. The increase in NH3 with stimulation was significantly larger in hyperoxia. Activity decreased alpha-ketoglutarate in hyperoxia but not in air. At stimulation, the estimated mitochondrial NAD+/NADH increased in both groups suggesting that hypoxia was not present. Thus hyperoxia did not affect mitochondrial redox state or lactate production and release in active muscle.

Animals↗

Skeletal muscle lactate release and glycolytic intermediates during hypercapnia.

The effects of respiratory acidosis on glycolysis in the autoperfused canine gastrocnemius-plantaris were studied using anesthetized dogs that were ventilated either with air (n = 30) or with 4% CO2-21% O2-75% N2 (n = 30). The left muscle group was stimulated at 3 Hz for up to 20 min, after which the active and the contralateral resting muscles were removed and frozen in liquid N2. Blood flow, VO2, Vco2, and tension development were unaffected by CO2. Glycogen catabolism was not affected, but lactate release (La) was lower (P less than 0.05) during activity with CO2; and greater fructose 6-phosphate, fructose 6-phosphate/fructose 1,6-diphosphate, and alpha-glycerophosphate/dihydroxyacetone phosphate ratios resulted (P less than 0.05). With respiratory acidosis, muscle lactate tended to accumulate early in contractions, but a net lactate uptake occurred during the last 10 min of contractions. Thus, respiratory acidosis reduced lactate efflux and there was a net uptake late in the contraction period. Glycogen phosphorylase did not appear to be affected by the respiratory acidosis, but there was evidence of inhibition at the phosphofructokinase step as well as a tendency for lactate to accumulate within the muscle. La often occurred in a direction contrary to the muscle-venous lactate concentration difference with either air or CO2 and La also decreased far more rapidly over time than did the arterial-venous H+.

Acidosis, Respiratory↗

A delivery-independent blood flow effect on skeletal muscle fatigue.

The hypothesis that hyperperfusion decreases muscle fatigue by increasing O2 and substrate delivery to the muscle was tested. Canine gastrocnemius-plantaris in situ preparations were stimulated at 5 Hz for 4 min during a free-flow control period and for 20 min during a pump-perfused experimental period. O2 delivery during these two periods was matched either by decreasing blood flow in animals breathing 100% O2 (high O2/low flow) [experimental-to-control ratio (E/C) = 0.97 + 0.02] or by increasing the blood flow in animals breathing 14% O2 (low O2/high flow) (E/C = 1.01 + 0.01). Plasma flow estimated from hematocrit to approximate substrate delivery was matched in the two contraction periods either by maintaining blood flow at the steady-state level (constant flow) (E/C = 0.98 + 0.10) or by increasing flow in animals with a dextran for 6% of blood volume exchange (dilute/high flow) (E/C = 1.02 + 0.02). E/C for initial developed tension was 1.00 + 0.02. Over 20 min, developed tension decreased 15.0 + 1.1% with low O2/high flow and 16.0 + 1.8% with dilute/high flow. Tension decreased by 28.0 + 3.0 and 27.8 + 1.5% with high O2/low flow and constant flow, respectively. Thus hyperperfusion decreased fatigue by a mechanism independent of increased O2 and substrate delivery.

Animals↗

Metabolic factors from exercising muscle and the proliferation of endothelial cells.

In order to identify factors that may be involved in angiogenesis in mammalian skeletal muscle after endurance exercise, the growth of cultured vascular endothelial cells derived from the canine hindlimb was measured in response to hypoxia and changes in temperature and concentrations of hydrogen ion and adenosine. Endothelial cells were freed from vessels of exsanguinated canine hindlimbs using collagenase. Cultures were grown on plastic culture dishes at 37 degrees C and 40 torr CO2 in air. Primary cultures reached confluency by 21 days. Cell number in secondary cultures was significantly increased in 7 days by exposure to 35 torr oxygen for 1 h daily, but cell growth rate was unaffected by 65 torr oxygen. Cell growth was inhibited when hydrogen ion concentration was increased by adding lactic acid daily (5 mmol X l-1). Exposing cell cultures for 1 h daily to an elevated PCO2 (70 torr) or to an environmental temperature of 41 degrees C, adding sodium lactate (5 mmol X l-1), or adenosine (10 or 100 mumol X l-1) daily did not affect cell growth rate. Thus, hypoxia increased the growth rate of cultured vascular endothelial cells and may play a role in blood vessel growth in vivo.

Adenosine↗

Midazolam and diazepam compared as sedatives for outpatient surgery under local analgesia.

Patients who had given their informed consent took part in a study to compare the sedative properties of the new benzodiazepine, midazolam, with diazepam. The drugs were administered intravenously and the quality of sedation, profoundness of amnesia, and rate of recovery were examined. Both drugs provided good-quality sedation, with midazolam producing a significantly greater degree of amnesia. Psychomotor tests used to assess recovery showed that patient performance following exposure to either drug had returned to normal 2 hours postsedation. However, patients who had received diazepam were drowsier later in the day and during the night following sedation than those who received midazolam. The implications of these findings are discussed.

Adolescent↗

Variations in amnesia with intravenous diazepam.

Volunteer senior students who had not previously received a benzodiazepine were employed to determine whether amnesia induced by the intravenous administration of diazepam remained constant. Profoundness of amnesia was tested 24 hours after drug administration following a first and second exposure to the drug. The two experiences were set 28 days apart. The study showed that recall of events in the immediate post-drug administration period was likely to be less impaired following a second exposure to diazepam than following the first. It also revealed that recall of visual stimuli was significantly better than recall of cutaneous-tactile stimuli. The clinical implications of these findings are discussed.

Amnesia↗

Energetics of mammalian fast and slow twitch muscles.

Myothermic determinations of the energetics of rat fast twitch extensor digitorum longus (EDL) and slow twitch soleus (SOL) reveal that at birth the total energy production is similar but by 41 days postpartum, the total energy production of the EDL is much greater, The higher energy liberation of EDL also exists in the mature mouse. The differences in total energy production result from higher values for both tension-independent and tension-dependent heat in the EDL. The heat-load relations of the two muscles are similar and were temperature- and initial length-dependent. Recovery in EDL is glycolytic in nature whereas mitochondrial oxidation predominates in the SOL. Quantitative differences exist between mature mammalian fast and slow twitch muscles that result from basic differences in excitation-contraction coupling, maximum velocity of shortening, and the muscle's enzymatic characteristics.

Animals↗

Diazepam and lorazepam compared as sedatives for outpatient third molar surgery.

A clinical trial was designed to compare diazepam and lorazepam when administered intravenously immediately prior to third molar surgery. The two drugs were compared on three scores, patient behaviour during surgery, presence of amnesia and extent of psychomotor impairment. Within the confines of the investigation the principle difference between diazepam and lorazepam was the greater degree of psychomotor impairment induced by the latter drug two hours post-injection.

Adolescent↗

Exercise efficiency: validity of base-line subtractions.

In evaluating the efficiency of humans performing exercise, base-line subtractions have been used in an attempt to determine the efficiency of the muscles in performing the external work. Despite the fact that base lines have been criticized previously, they have been widely used without adequate analysis of the implications involved. Calculations of efficiencies using data available in the literature for isolated muscle preparations revealed that base-line subtractions result in unreasonably high efficiencies. This suggests strongly that the base lines are invalid. To be valid, a base line must continue unchanged under all the conditions in which it is applied. Previously published data indicate clearly that exercise base lines change with increasing work rate and are therefore invalid. The use of base lines is further complicated by elastic energy storage in some types of exercise. Although exercise efficiencies using base line subtractions may be useful, they do not indicate muscle efficiency. Perhaps future studies of exercise metabolism should be directed less at refining base lines and more toward describing and quantifying the determinants of energy expenditure.

Efficiency↗

Interaction of hyperoxia and blood flow during fatigue of canine skeletal muscle in situ.

Right and left gastrocnemius-plantaris muscle preparations in 20 dogs anesthetized with pentobarbital sodium were used to investigate the effect of hyperoxia on tension maintenance. Muscles were stimulated via the sciatic nerve for 20 min at 60 200-ms tetanic contractions/min (10 impulses/contraction). Direct muscle stimulation after the experimental period resulted in no significant change in tension. In control experiments the tension developed by the right or left muscles over the 20 min was not different. The tension developed by muscles perfused with hyperoxic blood decreased 14% after 20 min, whereas tension in the normoxic muscles decreased 35%. Blood flow in the hyperoxic muscles was significantly higher at 20 min (P less than 0.05). Pump perfusion of one of a pair of normoxic muscles resulted in a tension decrease of 13% in the pump-perfused muscles, whereas tension in the control muscles decreased 34%. Tension maintenance was flow dependent. The effect of hyperoxia could be mediated through the involvement of oxygen in the long-term control of muscle blood flow.

Animals↗

Physiological characteristics of skeletal muscles of dogs and cats.

Our purpose was to determine if physiological characteristics of skeletal muscles of dogs and cats are related to their histochemical and biochemical characteristics. Maximum oxygen consumption (VO2max) and blood flow (Q) at VO2max were determined for in situ muscles of dogs and cats. Compared to cat muscles, dog muscles per unit mass had higher succinate oxidase activities, VO2max's, and Q's at VO2max's. There are positive relationships between Q at VO2max and VO2max and between VO2max and succinate oxidase activity. The higher VO2max's and succinate oxidase activities of dog muscles are consistent with the presence in these muscles of only slow-twitch fatique-resistant fibers and fast-twitch fatique-resistant fibers, whereas up to 50% of the fibers found in cat muscles are fast-twitch fatiqable. Capillary-to-fiber ratios are 2.40-2.97 for dog muscles compared to 2.17-2.84 for cat muscles. Thus the two- to threefold higher Q at VO2max for dog muscles compared to cat muscles is not due to a greater number of capillaries.

Animals↗