Influence of G-suit abdominal bladder inflation on gas exchange during +GZ stress

Available data relating duration of +GZ stress to blood gas exchange status is limited. Furthermore, studies focusing on pulmonary gas exchange during +GZ stress when abdominal restriction is imposed have yielded conflicting results. To examine the time course of blood gas changes occurring during exposure to +GZ stress in dogs and the influence of G-suit abdominal bladder inflation on this time course, seven spontaneously breathing pentobarbital-anesthetized adult mongrel dogs were exposed to 60 s of up to +5 GZ stress with and without G-suit abdominal bladder inflation. Arterial and mixed venous blood were sampled for blood gas analysis during the first and last 20 s of the exposure and at 3 min postexposure. Little change in blood gas status was seen at +3 GZ regardless of G-suit status. However, with G-suit inflation, arterial PO2 fell by a mean of 14.7 Torr during the first 20 s at +4 Gz (P less than 0.01, t test) and 20.6 Torr at +5 GZ (P less than 0.01). It continued to fall an additional 10 Torr during the next 40 s at both +4 and +5 GZ. Arterial PO2 was still 5-10 Torr below control values (P less than 0.05) 3 min postexposure. A second series of experiments paralleling the first focused on blood gas status during repeated exposure to acceleration. Blood gas status was assessed in five dogs during the late 20 s of two 60-s exposures separated by 3 min at 0 GZ. No significant differences between the initial and repeated exposures were detected. The data indicate that G-suit abdominal bladder inflation promotes increased venous admixture.     

Role of frequency and amplitude of repetitive HCG stimulations for sustained progesterone secretion from the bovine corpus luteum in vitro.

This investigation aimed at evaluating a role for frequencies and amplitudes of repeated HCG stimulations for the optimal maintenance of progesterone (P4) secretion from the bovine corpus luteum in vitro. Slices (100-120 mg) of midluteal bovine corpora lutea were perifused with medium M199 (0.05% BSA, pH 7.2, 38.5 degrees C) and the perifusion effluent collected at 15 minute intervals for 20-29 hours. Unstimulated P4 release (n = 5) was distinctly pulsatile (by Pulsar pulse algorithm), with pulses occurring every 90 +/- 6 minutes (mean +/- SEM) and pulse amplitudes of 14.4 +/- 1.1 ng. Conversely, no pulses were detected in two control perifusions. Unstimulated P4 release increased during the first 5 perifusion hours (from 39.3 +/- 4.6 to 50.3 +/- 5.6 ng/15 min, p less than 0.01), but then appeared to decline (to 29.3 +/- 1.3 ng/15 min, p less than 0.05) towards the end of the perifusion periods. Hourly pulses of HCG (6.7 mM) did not change the P4 pulse amplitudes (16.6 +/- 2.0 ng), the pulse periodicities (105 +/- 15 min) and overall release rates (34.7 +/- 5.7 ng/15 min), nor did they prevent the decline in P4 secretion towards the end of perifusions (n = 5). In contrast, 2-hourly HCG stimulations maintained stable P4 release rates throughout the perifusion periods (34.7 +/- 6.8 ng/15 min), with P4 pulses of similar amplitudes (14.7 +/- 1.7 ng), but of lower periodicities (135 +/- 2 min, p less than 0.05) than during unstimulated conditions (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cutaneous vascular responses to isometric handgrip exercise

Cutaneous vascular responses to dynamic exercise have been well characterized, but it is not known whether that response pattern applies to isometric handgrip exercise. We examined cutaneous vascular responses to isometric handgrip and dynamic leg exercise in five supine men. Skin blood flow was measured by laser-Doppler velocimetry and expressed as laser-Doppler flow (LDF). Arterial blood pressure was measured noninvasively once each minute. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure. LDF and CVC responses were measured at the forearm and chest during two 3-min periods of isometric handgrip at 30% of maximum voluntary contraction and expressed as percent changes from the preexercise levels. The skin was normothermic (32 degrees C) for the first period of handgrip and was locally warmed to 39 degrees C for the second handgrip. Finally, responses were observed during 5 min of dynamic two-leg bicycle exercise (150-175 W) at a local skin temperature of 39 degrees C. Arm LDF increased 24.5 +/- 18.9% during isometric handgrip in normothermia and 64.8 +/- 14.1% during isometric handgrip at 39 degrees C (P less than 0.05). Arm CVC did not significantly change at 32 degrees C but significantly increased 18.1 +/- 6.5% during isometric handgrip at 39 degrees C (P less than 0.05). Arm LDF decreased 12.2 +/- 7.9% during dynamic exercise at 39 degrees C, whereas arm CVC fell by 35.3 +/- 4.6% (in each case P less than 0.05). Chest LDF and CVC showed similar responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Time-motion and physiological assessments of ice hockey performance.

Ice hockey performance was studied during 10 contests to assess time-motion characteristics and associated physiological changes that occur for each position. Depending on the position played, the actual playing time per game for forwards and defensemen ranged between 20.7 and 28.0 min. The number of shifts ranged from 14 to 21 with an average playing time of 85.4 s/shift. Further analysis of each shift indicated that there was an average of 2.3 play stoppages which averaged 27.1 s, producing a continuous playing time of 39.7 s. Telemetered recordings of heart rate during each shift revealed sustained rates of between 170 and 174 beats/min over the three periods of the game. For both the forwards and defensemen, values for blood lactates were highest during the first and second periods (x = 78.0 and 66.1 mg/100 ml), then declined considerably during the third period (x = 44.5 mg/100 ml). Blood glucose showed a similar tendency (x = 139.3, 133.7, 114.1 mg/100 ml), while hematocrit and total protein showed little tendency to change.     

Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope

The importance of cardiac output (CO) to blood pressure level during vasovagal syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients, CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min, respectively. In TS patients, CO decreased during the first minute (from 3.3 +/- 0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001) than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in CO may contribute to hypotension some minutes before syncope occurs.     

Unlike mice, dogs exhibit effective glucoregulation during low-dose portal and peripheral glucose infusion

Portal infusion of glucose in the mouse at a rate equivalent to basal endogenous glucose production causes hypoglycemia, whereas peripheral infusion at the same rate causes significant hyperglycemia. We used tracer and arteriovenous difference techniques in conscious 42-h-fasted dogs to determine their response to the same treatments. The studies consisted of three periods: equilibration (100 min), basal (40 min), and experimental (180 min), during which glucose was infused at 13.7 micromol.kg(-1).min(-1) into a peripheral vein (p.e., n = 5) or the hepatic portal (p.o., n = 5) vein. Arterial blood glucose increased approximately 0.8 mmol/l in both groups. Arterial and hepatic sinusoidal insulin concentrations were not significantly different between groups. p.e. exhibited an increase in nonhepatic glucose uptake (non-HGU; Delta8.6 +/- 1.2 micromol.kg(-1).min(-1)) within 30 min, whereas p.o. showed a slight suppression (Delta-3.7 +/- 3.1 micromol.kg(-1).min(-1)). p.o. shifted from net hepatic glucose output (NHGO) to uptake (NHGU; 2.5 +/- 2.8 micromol.kg-1.min-1) within 30 min, but p.e. still exhibited NHGO (6.0 +/- 1.9 micromol.kg(-1).min(-1)) at that time and did not initiate NHGU until after 90 min. Glucose rates of appearance and disappearance did not differ between groups. The response to the two infusion routes was markedly different. Peripheral infusion caused a rapid enhancement of non-HGU, whereas portal delivery quickly activated NHGU. As a result, both groups maintained near-euglycemia. The dog glucoregulates more rigorously than the mouse in response to both portal and peripheral glucose delivery.     

Effect of exercise intensity on the slow component of oxygen uptake in decremental work load exercise.

The paper sought to determine the exercise intensity where the slow component of oxygen uptake (Vo(2)) first appears in decremental work load exercise (DLE). Incremental work load exercise (ILE) was performed with an increment rate of 15 watts (W) per minute. In DLE, power outputs were decreased by 15 W per minute, from 120 (DLE(120)), 160 (DLE(160)), 200 (DLE(200)) and 240 (DLE(240)) W, respectively. The slopes of Vo(2) against the power output were obtained in the lower section from 0 to 50 W in all DLEs, and in the upper section from 80 to 120 W in DLE(160) and from 100 to 150 W in DLE(200) and DLE(240). The power output at exhaustion in ILE was 274 +/- 20 W. The power output at the ventilatory threshold (VT) obtained in ILE was 167 +/- 22 W. The initial power output in DLE(160) was near the power output at VT. The slopes obtained in the upper sections were 11.4 +/- 0.9 ml x min(-1) x W(-1)1 in DLE(160), 12.8 +/- 0.8 ml x min(-1) x W(-1) in DLE(200), and 14.8 +/- 1.1 ml x min(-1) x W(-1) in DLE(240). The slope obtained in DLE(120) was 10.9 +/- 0.6 ml x min(-1). There were no differences in slope between the upper and lower sections in DLE(160) but there were significant differences in slopes between the upper and lower sections in DLE(200) and DLE(240). Thus, the slow component, which could be observed as a steeper slope in DLE, began to increase when the initial power output in DLE was near to VT.     

Comparison of a kayaking ergometer protocol with an arm crank protocol for evaluating peak oxygen consumption

The purpose of this study was to compare a kayak ergometer protocol with an arm crank protocol for determining peak oxygen consumption (V(.-)O2). On separate days in random order, 10 men and 5 women (16-24 years old) with kayaking experience completed the kayak ergometer protocol and a standardized arm crank protocol. The kayak protocol began at 70 strokes per minute and increased by 10 strokes per minute every 2 minutes until volitional fatigue. The arm crank protocol consisted of a crank rate of 70 revolutions per minute, initial loading of 35 W and subsequent increases of 35 W every 2 minutes until volitional fatigue. The results showed a significant difference (p < 0.01) between the kayak ergometer and the arm crank protocols for relative peak V(.-)O2 (47.5 +/- 3.9 ml x kg(-1) x min(-1) vs. 44.2 +/- 6.2 ml x kg(-1) x min(-1)) and absolute peak V(.-)O2 (3.38 L x min(-1) +/- 0.53 vs. 3.14 +/- 0.64 L x min(-1)). The correlation between kayak and arm crank protocol was 0.79 and 0.90, for relative and absolute V(.-)O2 peak, respectively (both p < 0.01). The higher peak V(.-)O2 on the kayak ergometer may be due to the greater muscle mass involved compared to the arm crank ergometer. The kayak ergometer protocol may therefore be more specific to the sport of kayaking than an arm crank protocol.     

Prior exercise enhances passive absorption of intraduodenal glucose.

The purpose of this study was to assess whether a prior bout of exercise enhances passive gut glucose absorption. Mongrel dogs had sampling catheters, infusion catheters, and a portal vein flow probe implanted 17 days before an experiment. Protocols consisted of either 150 min of exercise (n = 8) or rest (n = 7) followed by basal (-30 to 0 min) and a primed (150 mg/kg) intraduodenal glucose infusion [8.0 mg x kg-1x min-1, time (t) = 0-90 min] periods. 3-O-[3H]methylglucose (absorbed actively, facilitatively, and passively) and l-[14C]glucose (absorbed passively) were injected into the duodenum at t = 20 and 80 min. Phloridzin, an inhibitor of the active sodium glucose cotransporter-1 (SGLT-1), was infused (0.1 mg x kg-1 x min-1) into the duodenum from t = 60-90 min with a peripheral venous isoglycemic clamp. Duodenal, arterial, and portal vein samples were taken every 10 min during the glucose infusion, as well as every minute after each tracer bolus injection. Net gut glucose output in exercised dogs increased compared with that in the sedentary group (5.34 +/- 0.47 and 4.02 +/- 0.53 mg x kg-1x min-1). Passive gut glucose absorption increased approximately 100% after exercise (0.93 +/- 0.06 and 0.45 +/- 0.07 mg x kg-1 x min-1). Transport-mediated glucose absorption increased by approximately 20%, but the change was not significant. The infusion of phloridzin eliminated the appearance of both glucose tracers in sedentary and exercised dogs, suggesting that passive transport required SGLT-1-mediated glucose uptake. This study shows 1). that prior exercise enhances passive absorption of intraduodenal glucose into the portal vein and 2). that basal and the added passive gut glucose absorption after exercise is dependent on initial transport of glucose via SGLT-1.     

Adrenergic regulation of HSL serine phosphorylation and activity in human skeletal muscle during the onset of exercise

Skeletal muscle hormone-sensitive lipase (HSL) activity is increased by contractions and increases in blood epinephrine (EPI) concentrations and cyclic AMP activation of the adrenergic pathway during prolonged exercise. To determine the importance of hormonal stimulation of HSL activity during the onset of moderate- and high-intensity exercise, nine men [age 24.3 +/- 1.2 yr, 80.8 +/- 5.0 kg, peak oxygen consumption (VO2 peak) 43.9 +/- 3.6 ml x kg(-1) x min(-1)] cycled for 1 min at approximately 65% VO2 peak, rested for 60 min, and cycled at approximately 90% VO2 peak for 1 min. Skeletal muscle biopsies were taken pre- and postexercise, and arterial blood was sampled throughout exercise. Arterial EPI increased (P < 0.05) postexercise at 65% (0.45 +/- 0.10 to 0.78 +/- 0.27 nM) and 90% VO2 peak (0.57 +/- 0.34 to 1.09 +/- 0.50 nM). HSL activity increased (P < 0.05) following 1 min of exercise at 65% VO2 peak [1.05 +/- 0.39 to 1.78 +/- 0.54 mmol x min(-1) x kg dry muscle (dm)(-1)] and 90% VO2 peak (1.07 +/- 0.24 to 1.91 +/- 0.62 mmol x min(-1) x kg dm(-1)). Cyclic AMP content also increased (P < 0.05) at both exercise intensities (65%: 1.52 +/- 0.67 to 2.75 +/- 1.12, 90%: 1.85 +/- 0.65 to 2.64 +/- 0.93 micromol/kg dm). HSL Ser660 phosphorylation (approximately 55% increase) and ERK1/2 phosphorylation ( approximately 33% increase) were augmented following exercise at both intensities, whereas HSL Ser563 and Ser565 phosphorylation were not different from rest. The results indicate that increases in arterial EPI concentration during the onset of moderate- and high-intensity exercise increase cyclic AMP content, which results in the phosphorylation of HSL Ser660. This adrenergic stimulation contributes to the increase in HSL activity that occurs in human skeletal muscle in the first minute of exercise at 65% and 90% VO2 peak.     

Sympathetic adaptations to one-legged training.

The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P < 0.01). At rest, heart rate decreased from 77 +/- 3 to 71 +/- 6 beats/min (P < 0.01) with no significant changes in MAP (91 +/- 7 to 91 +/- 11 mmHg) and MSNA (29 +/- 3 to 28 +/- 1 bursts/min). During exercise, both heart rate and MAP were lower after training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P < 0.01). MSNA decreased similarly from rest during the first 2 min of exercise both before and after training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P < 0.01). This training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.     

Contribution of erythrocytes to the control of the electrolyte changes of exercise

Five healthy males performed four 30-s bouts of maximal isokinetic cycling with 4 min rest between each bout. Arterial and femoral venous blood was sampled during and for 90 min following exercise. During exercise, arterial erythrocyte [K+] increased from 117.0 +/- 6.6 mequiv./L at rest to 124.2 +/- 5.9 mequiv./L after the second exercise bout. Arterial erythrocyte [K+] returned to the resting values during the first 5 min of recovery. No significant change was observed in femoral venous erythrocyte [K+]. Arterial erythrocyte lactate concentration ([Lac-]) increased during exercise from 0.2 +/- 0.1 mequiv./L peaking at 9.5 +/- 1.5 mequiv./L at 5 min of recovery, after which the values returned to control. Femoral venous erythrocyte [Lac-] changed in a similar fashion. Arterial erythrocyte [Cl-] rose during exercise to 76 +/- 3 mequiv./L and returned to resting values (70 +/- 2 mequiv./L) by 25 min recovery. During exercise there was a net flux of Cl- into the erythrocyte. We conclude that erythrocytes are a sink for K+ ions leaving working muscles. Furthermore, erythrocytes function to transport Lac- from working muscle and reduce plasma acidosis by uptake of Cl-. The erythrocyte uptake of K+, Lac-, and Cl- helps to maintain a concentration difference between plasma and muscle, facilitating diffusion of Lac- and K+ from the interstitial space into femoral venous plasma.     

Blood flow, PO2, PCO2 and pH during progressive working contractions in a whole muscle group

Alterations in blood flow during progressive working contractions were examined to elucidate their relation to work rate in a predominantly glycolytic muscle group, i.e., m. gastrocnemius and m. plantaris, in rabbits anesthetized with urethane and chloralose. In one series of animals, the sciatic nerve was stimulated to induce plantar flexions of constant length at 2, 5 and 8% of an afterload at which only isometric tension could be developed. Another series was exercised at 30 and 50% of this value, and a third group served as non-exercised controls. Each experimental session consisted of a series of 5 min non-exercise periods followed by 6 min exercise periods, and a 10 min post-exercise period. Femoral venous blood was obtained just before the first exercise period, during the final minute of each exercise period, and 10 min after the final exercise period. The composition of venous blood samples from control animals did not change during the experimental session. Blood flow in the exercising limb increased at the lowest workload, and attained a maximum flow rate at the 5% workload. Blood gases were altered to a similar extent at all afterloads, averaging: PO2 = 4.0 +/- 0.2 kPa and PCO2 = 7.5 +/- 0.3 kPa. pH, in contrast, was lower at the heaviest afterloads (X = 7.144 +/- 0.03) compared to the lighter afterloads (X = 7.245 +/- 0.03). The blood flow and pH patterns are consistent with the glycolytic fiber type composition of this muscle group. Venous PO2 indicates that O2 delivery was adequate, even at the highest afterload.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory changes during exercise and arterial PCO2 oscillations in chronic airway obstruction patients

Ventilatory kinetics during exercise (30 W for 6 min) were studied in 3 asthmatics, 14 patients with chronic airway obstruction (11 with bronchial or type B disease, 3 with emphysematous or type A disease), and in 5 normal age-matched controls. The measure of ventilatory increase during early exercise, alpha 1-3%, was calculated as (avg minute ventilation over 1st-3rd min of exercise--resting minute ventilation)/(avg minute ventilation over 4th-6th min of exercise--resting minute ventilation) X 100. Arterial pH, PO2, and PCO2 (PaCO2) were measured in vitro at rest and within 20 s of termination of exercise. Respiratory PaCO2 oscillations had previously been monitored at rest in the patients (indirectly as in vivo arterial pH, using a fast-response pH electrode) and quantified by upslope (delta PaCO2/delta t). alpha 1-3% was normal in asthmatics (whose respiratory oscillations as a group showed least attenuation) and in type A patients (whose respiratory oscillations as a group were most attenuated). In type B patients reduction in alpha 1-3% correlated with attenuation of delta PaCO2/delta t (r = 0.75; P less than 0.01). There was no significant correlation between delta PaCO2/delta t and change of in vitro PaCO2 from rest to the immediate postexercise period. These findings are consistent with the hypothesis that attenuation of delta PaCO2/delta t slows ventilatory kinetics during exercise in type B but not type A patients. Intact respiratory oscillations are not necessary for CO2 homeostasis after the first few minutes of exercise.     

Cardiorespiratory response to absolute and relative work intensity in untrained men

Twenty young, untrained men performed two tests on cycle ergometer in order to verify whether the kinetics of the cardiorespiratory reactions exhibit any relation to maximal oxygen uptake (VO2max) in the untrained state. On the 1st day, the subjects exercised at work intensities of 50 and 100 W, the increase as a step function, for periods of 10 min each. The next day, they performed exercise at a relative intensity of 50% VO2max for 10 min. Respiratory frequency, tidal volume, minute ventilation (VE), heart rate (HR), stroke volume (SV), and cardiac output (Q) were measured continuously. The SV was measured by impedance plethysmography. All the cardiorespiratory variables increased rapidly at the onset of both absolute and relative intensity of work, with a faster response for Q than for VE. The increase in absolute intensity of work from 50 to 100 W caused a significantly slower cardiorespiratory reaction than at the beginning of exercise. The SV increased by 20 ml during first 20 s of both absolute and relative intensities of work and then began to decrease after 6 and 4 min of the exercise, respectively. The decrease in SV was associated with an increase in HR and a stable value of Q. Acceleration at the beginning of, and deceleration during recovery from, the relative intensity of work for VE, HR, and Q were well correlated with individual levels of VO2max in the tested men. It is concluded that the kinetics of cardiorespiratory reaction to a constant, relative intensity of work is related to VO2max in untrained men, and that the kinetics probably constitute a physiological feature of an individual.     

CEREBRAL METABOLIC CHANGES DURING PROLONGED EPILEPTIC SEIZURES IN RATS

Abstract— Sustained epileptic seizures were induced in paralysed, artificially ventilated and anaesthetized (70% N₂O) rats by means of intravenous bicuculline (1.2mgkg^?1), and cerebral cortical tissue was frozen in situ after periods varying between 10 s and 2 h for analyses of labile phosphates, glycolytic metabolites, citric acid cycle intermediates, and associated amino acids and ammonia, using enzymic fluorometric techniques. Body temperature was kept at 37°C, and arterial hypotension, arterial hypoxaemia and hypoglycaemia were prevented. Cortical glycogen concentrations fell progressively (to 23% of control levels) between 1 and 20 min after seizure onset but returned to control concentrations after 120 min of seizure activity. Cortical glucose concentration fell to 30% of control after 1 min of seizure activity, remained close to 50% of control for 1 h, and fell again to 30% after 2 h of seizure activity. Cortical lactate concentration was doubled in brains frozen 10 s after bicuculline injection. It rose over the following 20 min, reaching a steady concentration of about 10μmolg^?1 wet wt. The changes in lactate and glucose concentration indicated a 34-fold increase in the rate of glycolysis during the first minute of seizure. Phosphocreatine concentration was reduced by nearly 50% after 10 and 30 s of seizure activity, and subsequently stabilized at a concentration 2/3 of normal. ATP concentration was maximally reduced (by 7%) after 30 s and remained close to normal thereafter. Larger, initial reductions occurred in ATP/ADP and ATP/ AMP ratios, as well as in the adenylate energy charge. All these parameters remained significantly reduced for the rest of the 2 h seizure period. However, the changes were moderate since the energy charge was maintained within 2% of control. Changes in citric acid cycle intermediates included initial reductions in α-ketoglutarate and oxaloacetate (calculated) and progressive increases in fumarate, malate and citrate. After long periods of seizures all citric acid cycle intermediates except oxaloacetate were increased in concentration. Ammonia increased during the first min to reach steady state values of 200% of control. Alanine increased progressively during the first 20 min, to stabilize at 200% of control thereafter. GABA increased at 5 min and subsequently rose to almost twice the control value (120 min). At 20 min and onwards there were progressive decreases in glutamate and aspartate, and a progressive increase in glutamine. The sum of amino acids measured increased significantly and the sum of ammonia equivalents rose substantially. Intracellular pH calculated from the creatine kinase equilibrium decreased by 0.25 units during the first minute. However, since the pH calculated from P_co, and cellular buffer base changes remained close to normal during this period, it is concluded that the components of the creatine kinase reaction were not in equilibrium, and the pH values calculated from this equilibrium were incorrect. Tentative calculations of NADH/NAD⁺ ratios indicated that redox changes of opposite direction occurred in cytoplasm (reduction) and mitochondria (oxidation).     

Effect of somatostatin on renal function.

Somatostatin has profound effects on both splanchnic and portal vascular beds. The effects of intravenous somatostatin (100 micrograms/h) on urinary volume, effective renal plasma flow, and glomerular filtration rate were compared with the effects of a control infusion of physiological saline in six normal subjects. Renal plasma flow and glomerular filtration rate were measured by primed constant isotope infusions of iodine-125 iodohippurate and chromium-51 edetic acid. Urinary volume, renal plasma flow, and glomerular filtration rate were measured during 20 minute clearance periods. During the control infusion urinary volume, renal plasma flow, and glomerular filtration rate remained essentially unchanged at 254 (SEM 3) ml/20 min, 568 (5) ml/min/1.73 m2, and 110 (2) ml/min/1.73 m2 respectively. From similar basal values the infusion of somatostatin led to a rapid decrease in all three variables. After 120 minutes of infusion of somatostatin urinary volume, renal plasma flow, and glomerular filtration rate were reduced to 148 (17) ml/20 min (p less than 0.01), 422 (7) ml/min/1.73 m2 (p less than 0.001), and 93 (3) ml/min/1.73 m2 (p less than 0.05) respectively. This effect on renal function should be borne in mind whenever somatostatin is used.     

The direct effects of catecholamines on hepatic glucose production occur via alpha(1)- and beta(2)-receptors in the dog

The role of alpha- and beta-adrenergic receptor subtypes in mediating the actions of catecholamines on hepatic glucose production (HGP) was determined in sixteen 18-h-fasted conscious dogs maintained on a pancreatic clamp with basal insulin and glucagon. The experiment consisted of a 100-min equilibration, a 40-min basal, and two 90-min test periods in groups 1 and 2, plus a 60-min third test period in groups 3 and 4. In group 1 [alpha-blockade with norepinephrine (alpha-blo+NE)], phentolamine (2 microg x kg(-1) x min(-1)) was infused portally during both test periods, and NE (50 ng x kg(-1) x min(-1)) was infused portally at the start of test period 2. In group 2, beta-blockade with epinephrine (beta-blo+EPI), propranolol (1 microg x kg(-1) x min(-1)) was infused portally during both test periods, and EPI (8 ng x kg(-1) x min(-1)) was infused portally during test period 2. In group 3 (alpha(1)-blo+NE), prazosin (4 microg x kg(-1) x min(-1)) was infused portally during all test periods, and NE (50 and 100 ng x kg(-1) x min(-1)) was infused portally during test periods 2 and 3, respectively. In group 4 (beta(2)-blo+EPI), butoxamine (40 microg x kg(-1) x min(-1)) was infused portally during all test periods, and EPI (8 and 40 ng x kg(-1) x min(-1)) was infused portally during test periods 2 and 3, respectively. In the presence of alpha- or alpha(1)-adrenergic blockade, a selective rise in hepatic sinusoidal NE failed to increase net hepatic glucose output (NHGO). In a previous study, the same rate of portal NE infusion had increased NHGO by 1.6 +/- 0.3 mg x kg(-1) x min(-1). In the presence of beta- or beta(2)-adrenergic blockade, the selective rise in hepatic sinusoidal EPI caused by EPI infusion at 8 ng x kg(-1) x min(-1) also failed to increase NHGO. In a previous study, the same rate of EPI infusion had increased NHGO by 1.6 +/- 0.4 mg x kg(-1) x min(-1). In conclusion, in the conscious dog, the direct effects of NE and EPI on HGP are predominantly mediated through alpha(1)- and beta(2)-adrenergic receptors, respectively.     

Gamma-glutamylcysteine synthetase activity in human lung epithelial (A549) cells: factors influencing its measurement

Despite the central role of gamma-glutamylcysteine synthetase (gammaGCS) in lung antioxidant defenses, the limited studies of the activity of this enzyme in respiratory cells have produced variable results. This study has examined the factors, which may influence the measurement of gammaGCS activity in cultured human lung epithelial cells (A549). Although a source of potential error, gammaGCS activity in A549 cell extracts did not vary significantly when appropriately assayed by three different methods or after removal of the endogenous inhibitor, glutathione (GSH). However, gammaGCS activity did increase significantly during the early stages of cell proliferation (3.50 +/- 0.31 vs. 2.35 +/- 0.16 nmol/min/10(6) cells for baseline, p < .001) and thereafter returned to baseline levels during the later stages of cell growth. Variations in initial plating density also significantly altered gammaGCS activity (3.11 +/- 0.14 vs. 4.04 +/- 0.50 nmol/min/10(6) cells, at 0.25 x 10(5) and 0.58 x 10(5) cells/cm2, respectively, p < .001) and GSH content (45.43 +/- 4.43 vs. 63.64 +/- 3.28 nmol/10(6) cells at 0.25 x 10(5) and 0.58 x 10(5) cells/cm2, respectively, p < .001) during the early stages of cell proliferation. In addition, gammaGCS activity and GSH content were highest in A549 cells grown in medium containing cystine as the predominant sulfur-containing amino acid. These results suggest that gammaGCS activity of A549 cells is strongly dependent on initial plating density, stage of cell growth and sulfur amino acid content of the medium and may account for some of the variation in values reported by different investigators. Whether gammaGCS has an important role in the early phase of cell proliferation needs further investigation.     

Patterns of physical activity among 11 to 16 year old British children.

OBJECTIVE--To examine the patterns of physical activity among British schoolchildren aged 11 to 16 and to assess whether the children experience the intensity and duration of physical activity that are believed to stress the cardiopulmonary system appropriately. DESIGN--Cross sectional study of a sample of children drawn from a larger survey of coronary risk factors in children. Continuous monitoring of heart rate for 12 hour periods on three school days and one Saturday. SETTING--Two communities in Devon. SUBJECTS--266 Children (163 girls, 103 boys) aged 11 to 16 randomly selected from a sample of 707 children. MAIN OUTCOME MEASURES--Percentage of time and number of sustained periods in which heart rate was greater than 139 beats/min. Anthropometric measures and external assessment of sexual maturity with Tanner''s indices. RESULTS--The boys had heart rates greater than 139 beats/min for a significantly higher percentage of time than the girls (p less than 0.01) during the weekday (6.2% v 4.3%) and the Saturday (5.6% v 2.6%). The boys had significantly more five and 10 minute periods with heart rates greater than 139 beats/min than the girls during the Saturday and weekdays and more 20 minute periods during the weekdays. 84 Girls and 37 boys had no 10 minute period with a heart rate greater than 139 beats/min during the three weekdays and 112 girls and 65 boys had no such 10 minute period during the Saturday. No significant relation was detected in either sex between the amount or habitual physical activity (heart rate) and skinfold thickness or maturity group. CONCLUSIONS--British children have surprisingly low levels of habitual physical activity, and many children seldom undertake the volume of physical activity believed to benefit the cardiopulmonary system. Boys are more active than girls. The pubertal stage of development or body fatness, or both, do not seem to be sensitive indicators of physical activity in either girls or boys.