Epinephrine-induced changes in muscle carbohydrate metabolism during exercise in male subjects

Epinephrine increases glycogenolysis in resting skeletal muscle, but less is known about the effects of epinephrine on exercising muscle. To study this, epinephrine was given intraarterially to one leg during two-legged cycle exercise in nine healthy males. The epinephrine-stimulated (EPI) and non-stimulated (C) legs were compared with regard to glycogen, glucose, glucose 6-phosphate (G6P), alpha-glycerophosphate (alpha-GP), and lactate contents in muscle biopsies taken before and after the 45-min submaximal exercise, as well as brachial arterial-femoral venous (a-fv) differences for epinephrine, norepinephrine, lactate, glucose, and O2 during exercise. During exercise the arterial plasma epinephrine concentration was 4.8 +/- 0.8 nmol/l and the femoral venous epinephrine concentrations were 10.3 +/- 2.1 and 3.9 +/- 0.6 nmol/l, respectively, in the EPI and C leg. During exercise the a-fv difference for lactate was greater (-0.41 +/- 0.14 vs. -0.21 +/- 0.14 mmol/l; P less than 0.001), and the a-fv difference for glucose was smaller (0.07 +/- 0.12 vs. 0.24 +/- 0.12 mmol/l; P less than 0.01) in the EPI than in the C leg, but the a-fv differences for O2 were similar. Muscle glycogen depletion (137 +/- 63 vs. 99 +/- 43 mmol/kg dry muscle; P less than 0.1) and the muscle concentrations of glucose (P less than 0.05), alpha-GP (P less than 0.1), G6P (P greater than 0.1), and lactate (P greater than 0.1) tended to be higher in the EPI than the C leg after exercise. These findings suggest that physiological concentrations of epinephrine may enhance muscle glycogenolysis during submaximal exercise in male subjects.     

Human muscle metabolism during sprint running

Biopsy samples were obtained from vastus lateralis of eight female subjects before and after a maximal 30-s sprint on a nonmotorized treadmill and were analyzed for glycogen, phosphagens, and glycolytic intermediates. Peak power output averaged 534.4 +/- 85.0 W and was decreased by 50 +/- 10% at the end of the sprint. Glycogen, phosphocreatine, and ATP were decreased by 25, 64, and 37%, respectively. The glycolytic intermediates above phosphofructokinase increased approximately 13-fold, whereas fructose 1,6-diphosphate and triose phosphates only increased 4- and 2-fold. Muscle pyruvate and lactate were increased 19 and 29 times. After 3 min recovery, blood pH was decreased by 0.24 units and plasma epinephrine and norepinephrine increased from 0.3 +/- 0.2 nmol/l and 2.7 +/- 0.8 nmol/l at rest to 1.3 +/- 0.8 nmol/l and 11.7 +/- 6.6 nmol/l. A significant correlation was found between the changes in plasma catecholamines and estimated ATP production from glycolysis (norepinephrine, glycolysis r = 0.78, P less than 0.05; epinephrine, glycolysis r = 0.75, P less than 0.05) and between postexercise capillary lactate and muscle lactate concentrations (r = 0.82, P less than 0.05). The study demonstrated that a significant reduction in ATP occurs during maximal dynamic exercise in humans. The marked metabolic changes caused by the treadmill sprint and its close simulation of free running makes it a valuable test for examining the factors that limit performance and the etiology of fatigue during brief maximal exercise.     

Changes in the levels of growth hormones, insulin, cortisol, thyroxine and somatomedin-C/IGF-1, with increasing gestational age in the fetal pig, and the effect of thyroidectomy in utero

1. Blood samples were taken from 30 chronically catheterized pig fetuses in utero. Levels of growth hormone, insulin, cortisol, thyroxine and somatomedin-C/IGF-1 were measured in the plasma of intact fetuses and the plasma of thyroidectomized fetuses at various gestational ages during the latter part of pregnancy. 2. Growth hormone levels were high (mean +/- SEM: 83 +/- 9 ng/ml and remained constant throughout this period. 3. Insulin levels were also constant and ranged between 4 and 14 mU/l. 4. Cortisol levels showed a general increase from 400 nmol/l at 97 days to 1200 nmol/l at term and this increase was not affected by thyroidectomy. 5. IGF-1 levels were lower than in the sows (48.0 +/- 3.0 ng/ml) and did not change throughout this period. 6. Thyroxine levels were also unchanged at about 92 +/- 4 nmol/l. 7. Thyroidectomy resulted in lower (P less than 0.001) thyroxine levels (28 +/- 3 nmol/l) but had no effect on the levels of any other hormone.     

Effect of single wrist exercise on fibroblast growth factor-2, insulin-like growth factor, and growth hormone

Anabolic effects of exercise are mediated, in part, by fibroblast growth factor-2 (FGF-2), insulin-like growth factor-I (IGF-I), and growth hormone (GH). To identify local vs. systemic modification of these mediators, 10 male subjects performed 10 min of unilateral wrist-flexion exercise. Blood was sampled from catheters placed in basilic veins of both arms. Lactate was significantly increased only in the exercising arm. FGF-2 decreased dramatically (P < 0.01) in both the resting (from 1.49 +/- 0.32 to nadir at 0.11 +/- 0.11 pg/ml) and exercising arm (1.80 +/- 0.60 to 0.29 +/- 0.14 pg/ml). Small but significant increases were found in both the resting and exercising arm for IGF-I and IGF binding protein-3 (IGFBP-3). GH was elevated in blood sampled from both the resting (from 1.04 +/- 0.68 to a peak of 2.57 +/- 0.53 ng/ml) and exercising arm (1.04 +/- 0.66 to 2.43 +/- 0.42 ng/ml, P < 0.05). Unilateral wrist exercise was not sufficiently intense to increase circulating lactate or heart rate, but it led to systemic changes in GH, IGF-I, IGFBP-3, and FGF-2. Low-intensity exercise involving small muscle groups can influence the circulating levels of growth factors.     

Effects of synthetic atrial natriuretic factor (ANF) on renin-aldosterone axis in the conscious newborn calf

The effects of synthetic atrial natriuretic factor (ANF) on the renin-aldosterone axis were studied in fifteen 4-7 day-old male milk-fed calves divided into 3 groups of 5 animals each. Synthetic ANF intravenous (i.v.) administration (1.6 micrograms/kg body wt over 30 min) induced a transient significant fall in plasma renin activity (from 2.5 +/- 0.3 to 1.7 +/- 0.3 ng angiotensin l/ml/h; P less than 0.05) but failed to reduce basal plasma aldosterone levels in the first group of animals. Administration (i.v.) of angiotensin II (AII) (0.8 micrograms/kg body wt for 75 min) was accompanied by a progressive fall in plasma renin activity (from 2.2 +/- 0.3 to 0.8 +/- 0.1 ng angiotensin l/ml/h; P less than 0.01) and by an increase in plasma aldosterone levels (from 55 +/- 3 to 86 +/- 5 pg/ml; P less than 0.01) both in the second and the third groups; addition of ANF to AII infusion (AII: 0.5 mu/kg body wt for 45 min; AII: 0.3 micrograms/kg body wt and ANF 1.6 micrograms/kg body wt during 30 min) in the third group did not modify plasma renin activity or AII-stimulated plasma aldosterone levels when compared to the AII-treated group. These findings show that in the newborn calf ANF is able to reduce plasma renin activity but fails to affect basal and AII-stimulated plasma aldosterone levels, suggesting that the zona glomerulosa of the newborn adrenal cortex is insensitive to a diuretic, natriuretic and hypotensive dose of the atrial peptide.     

Response of thyrotropin, prolactin and free thyroid hormones to graded exercise in normal male subjects

Serum levels of thyrotrophin (TSH), prolactin (PRL), free thyroxine (FT4) and free triiodothyronine (FT3) were determined before and after physical exercise in 21 normal male subjects. The subjects were divided into 3 groups as follows: group I--light exercise (exercise on the Mijnhardt bicycle ergometer at 100 Watts for 15 min); group II--moderate exercise (a 5 km marathon); group III--heavy exercise (a 10 km marathon). In group I, TSH level rose from 1.96 +/- 0.42 mu u/ml (mean +/- SEM) to 2.52 +/- 0.30 mu u/ml (p less than 0.01), and PRL levels rose from 11.0 +/- 2.0 ng/ml to 19.0 +/- 5.2 ng/ml (p less than 0.01). In group II, TSH rose from 2.11 +/- 0.51 mu u/ml to 2.62 +/- 0.56 mu u/ml (p less than 0.05), and PRL rose from 11.2 +/- 1.6 ng/ml to 24.0 +/- 5.2 ng/ml (p less than 0.01). In group III, TSH rose from 2.01 +/- 0.41 mu u/ml to 2.36 +/- 0.45 mu u/ml (p less than 0.02), and PRL rose from 12.1 +/- 2.0 ng/ml to 47.7 +/- 9.3 ng/ml (p less than 0.01). The serum levels of FT4 showed different results among the three groups: Group I showed an increased response from 1.60 +/- 0.12 ng/dl to 1.72 +/- 0.12 ng/dl (p less than 0.01); Group II showed no significant difference; and group III demonstrated a diminished response from 1.61 +/- 0.14 ng/dl to 1.45 +/- 0.16 ng/dl (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular and hormonal adaptations in athletes to strength training in two years

Neuromuscular and hormonal adaptations to prolonged strength training were investigated in nine elite weight lifters. The average increases occurred over the 2-yr follow-up period in the maximal neural activation (integrated electromyogram, IEMG; 4.2%, P = NS), maximal isometric leg-extension force (4.9%, P = NS), averaged concentric power index (4.1%, P = NS), total weight-lifting result (2.8%, P less than 0.05), and total mean fiber area (5.9%, P = NS) of the vastus lateralis muscle, respectively. The training period resulted in increases in the concentrations of serum testosterone from 19.8 +/- 5.3 to 25.1 +/- 5.2 nmol/l (P less than 0.05), luteinizing hormone (LH) from 8.6 +/- 0.8 to 9.1 +/- 0.8 U/l (P less than 0.05), follicle-stimulating hormone (FSH) from 4.2 +/- 2.0 to 5.3 +/- 2.3 U/l (P less than 0.01), and testosterone-to-serum sex hormone-binding globulin (SHBG) ratio (P less than 0.05). The annual mean value of the second follow-up year for the serum testosterone-to-SHBG ratio correlated significantly (r = 0.84, P less than 0.01) with the individual changes during the 2nd yr in the averaged concentric power. The present results suggest that prolonged intensive strength training in elite athletes may influence the pituitary and possibly hypothalamic levels, leading to increased serum levels of testosterone. This may create more optimal conditions to utilize more intensive training leading to increased strength development.     

Tissue factor, tissue factor pathway inhibitor and cytoadhesive molecules in patients with an acute coronary syndrome

The tissue factor plays a crucial role in initiating blood coagulation after plaque rupture in patients with acute coronary syndrome. It is abundant in atherosclerotic plaques. Moreover, P-selectin, some cytokines, endotoxin and immune complexes can stimulate monocytes and induce the tissue factor expression on their surface. The aim of the study was to compare plasma levels of the tissue factor, tissue factor pathway inhibitor, P-selectin, E-selectin and ICAM-1 in patients with acute myocardial infarction, unstable angina pectoris, stable coronary artery disease and normal control subjects. In addition, plasma levels of the tissue factor, tissue factor pathway inhibitor, P-selectin, E-selectin and ICAM-1 were measured in the blood withdrawn from the coronary sinus in a subgroup of patients with unstable angina pectoris and stable coronary artery disease in which the difference between concentrations in the coronary sinus and systemic blood was calculated. A significant increase in tissue factor pathway inhibitor plasma levels was detected in patients with acute myocardial infarction (373.3+/-135.1 ng/ml, p<0.01) and unstable angina pectoris (119.6+/-86.9 ng/ml, p<0.05) in contrast to the patients with stable coronary artery disease (46.3+/-37.5 ng/ml) and normal subjects (45.1+/-14.3 ng/ml). The plasma levels of tissue factor pathway inhibitor were significantly increased both in the coronary sinus and systemic blood in the patients with unstable angina pectoris. There was only a non-significant trend to higher plasma levels of the tissue factor in patients with acute myocardial infarction and unstable angina pectoris as compared to the patients with stable coronary artery disease and normal subjects, the values being 129.1+/-30.2 pg/ml, 130.5+/-57.8 pg/ml, 120.2+/-45.1 pg/ml and 124.9+/-31.8 pg/ml, respectively. Plasma levels of soluble P-selectin was only slightly, but non-significantly higher in patients with unstable angina pectoris and stable coronary artery disease (184.2+/-85.4 ng/ml and 201.6+/-67.9 ng/ml, respectively) than in patients with the acute myocardial infarction (157.4+/-88.4 ng/ml) or normal subjects (151.4+/-47.1 ng/ml). The difference in plasma levels of soluble ICAM-1 between the blood withdrawn from the coronary sinus and systemic circulation correlated significantly with the corresponding difference in plasma levels of soluble P-selectin and E-selectin. In conclusion, the tissue factor and the tissue factor pathway inhibitor play a crucial role in the initiation of arterial thrombosis. The tissue factor pathway inhibitor levels are increased both in the systemic blood and in the coronary sinus of patients with the acute coronary syndrome.     

MCA Vmean and the arterial lactate-to-pyruvate ratio correlate during rhythmic handgrip.

Regulation of cerebral blood flow during physiological activation including exercise remains unknown but may be related to the arterial lactate-to-pyruvate (L/P) ratio. We evaluated whether an exercise-induced increase in middle cerebral artery mean velocity (MCA Vmean) relates to the arterial L/P ratio at two plasma lactate levels. MCA Vmean was determined by ultrasound Doppler sonography at rest, during 10 min of rhythmic handgrip exercise at approximately 65% of maximal voluntary contraction force, and during 20 min of recovery in seven healthy male volunteers during control and a approximately 15 mmol/l hyperglycemic clamp. Cerebral arteriovenous differences for metabolites were obtained by brachial artery and retrograde jugular venous catheterization. Control resting arterial lactate was 0.78 +/- 0.09 mmol/l (mean +/- SE) and pyruvate 55.7 +/- 12.0 micromol/l (L/P ratio 16.4 +/- 1.0) with a corresponding MCA Vmean of 46.7 +/- 4.5 cm/s. During rhythmic handgrip the increase in MCA Vmean to 51.2 +/- 4.6 cm/s was related to the increased L/P ratio (23.8 +/- 2.5; r2 = 0.79; P < 0.01). Hyperglycemia increased arterial lactate and pyruvate to 1.9 +/- 0.2 mmol/l and 115 +/- 4 micromol/l, respectively, but it did not significantly influence the L/P ratio or MCA Vmean at rest or during exercise. Conversely, MCA Vmean did not correlate significantly, neither to the arterial lactate nor to the pyruvate concentrations. These results support that the arterial plasma L/P ratio modulates cerebral blood flow during cerebral activation independently from the plasma glucose concentration.     

Insulinhypoglycemia but not arginine infusion stimulates circulating plasma growth hormone-releasing hormone (GHRH) concentrations in children

The effect of insulinhypoglycemia and arginine infusion on circulating concentrations of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) has been studied in 24 children (4.4 to 14.3 years). Plasma GH and GHRH concentrations were determined by RIA. Basal plasma GHRH levels were detectable in the plasma of all patients ranging from 6.8 to 27.1 pg/ml. Injection of 0.1 U/kg body wt. insulin i.v. resulted in an increase of plasma GHRH levels (11.1 +/- 1.4 pg/ml vs. 18.8 +/- 2.6 pg/ml; P less than 0.01) preceding that of plasma GH (1.5 +/- 0.4 ng/ml vs. 13.6 +/- 1.3 ng/ml; P less than 0.01). Infusion of 0.5 gm/kg body wt. arginine hydrochloride did increase GH concentrations (2.0 +/- 0.6 ng/ml vs. 13.9 +/- 2.3 ng/ml; P less than 0.01) but did not change circulating plasma GHRH levels. Since the source of peripheral GHRH concentrations is not known the importance of these findings remains to be determined.     

Endocrine profiles and embryo quality in the PMSG-PGF2alpha treated cow

Plasma progesterone and LH concentrations around estrus were determined for both PMSG treated (experimental animals) and non-treated (control animals) dairy cows and heifers of the Holstein Friesian and Jersey breeds, and these hormone profiles were related to the embryo quality. Most experimental animals experienced an increase in progesterone concentrations following PMSG treatment and an abrupt decrease to values below 3 nmol/l after PG injection. The mean (+/-SE) intervals from prostaglandin treatment to estrus were 46.9+/-1.8 h and 64.5+/-4.8 h for experimental and control animals, respectively. At the onset of heat the progesterone concentration in experimental animals with optimal embryo quality (group I) was significantly lower (p<0.01) than in experimental animals which yielded unfertilized eggs (group II) (1.2+/-0.1 versus 3.9+/-0.8 nmol/l) and significantly higher than the level in the control group (0.6+/-0.1 nmol/l). Following estrus the progesterone profiles in all 3 groups were studied and the length of the superovulatory cycle was measured to 26.0+/-4.8 days. The preovulatory LH surge occurred sooner after prostaglandin injection in experimental (41 h) than in control animals (65 h). The LH surge in group I occurred within a narrow range and reached a higher average level than group II (24.2+/-2.2 ng/ml and 16.3+/-3.7 ng/ml, respectively). The control group attained an even higher LH surge (31.8+/-8.8 ng/ml) than did the experimental animals. The data presented in this experiment indicate that plasma levels of progesterone and LH in PMSG-PGF(2)alpha treated animals are related to embryo or egg quality.     

Exercise intensity: effect on postexercise O2 uptake in trained and untrained women

Despite many reports of long-lasting elevation of metabolism after exercise, little is known regarding the effects of exercise intensity and duration on this phenomenon. This study examined the effect of a constant duration (30 min) of cycle ergometer exercise at varied intensity levels [50 and 70% of maximal O2 consumption (VO2max)] on 3-h recovery of oxygen uptake (VO2). VO2 and respiratory exchange ratios were measured by open-circuit spirometry in five trained female cyclists (age 25 +/- 1.7 yr) and five untrained females (age 27 +/- 0.8 yr). Postexercise VO2 measured at intervals for 3 h after exercise was greater (P less than 0.01) after exercise at 50% VO2max in trained (0.40 +/- 0.01 l/min) and untrained subjects (0.39 +/- 0.01 l/min) than after 70% VO2max in (0.31 +/- 0.02 l/min) and untrained subjects (0.29 +/- 0.02 l/min). The lower respiratory exchange ratio values (P less than 0.01) after 50% VO2max in trained (0.78 +/- 0.01) and untrained subjects (0.80 +/- 0.01) compared with 70% VO2max in trained (0.81 +/- 0.01) and untrained subjects (0.83 +/- 0.01) suggest that an increase in fat metabolism may be implicated in the long-term elevation of metabolism after exercise. This was supported by the greater estimated fatty acid oxidation (P less than 0.05) after 50% VO2max in trained (147 +/- 4 mg/min) and untrained subjects (133 +/- 9 mg/min) compared with 70% VO2max in trained (101 +/- 6 mg/min) and untrained subjects (85 +/- 7 mg/min).     

Effect of beta-adrenoceptor blockade on renin-aldosterone and alpha-ANF during exercise at altitude

The renin-aldosterone system may be depressed in subjects exercising at high altitude, thereby preventing excessive angiotensin I (ANG I) and aldosterone levels, which could favor the onset of acute mountain sickness. The role of beta-adrenoceptors in hormonal responses to hypoxia was investigated in 12 subjects treated with a nonselective beta-blocker, pindolol. The subjects performed a standardized maximal bicycle ergometer exercise with (P) and without (C) acute pindolol treatment (15 mg/day) at sea level, as well as during a 5-day period at high altitude (4,350 m, barometric pressure 450 mmHg). During sea-level exercise, pindolol caused a reduction in plasma renin activity (PRA, 2.83 +/- 0.35 vs. 5.13 +/- 0.7 ng ANG I.ml-1.h-1, P less than 0.01), an increase in plasma alpha-atrial natriuretic factor (alpha-ANF) level (23.1 +/- 2.9 (P) vs. 10.4 +/- 1.5 (C) pmol/1, P less than 0.01), and no change in plasma aldosterone concentration [0.50 +/- 0.04 (P) vs. 0.53 +/- 0.03 (C) nmol/1]. Compared with sea-level values, PRA (3.45 +/- 0.7 ng ANG I.ml-1.h-1) and PA (0.39 +/- 0.03 nmol/1) were significantly lower (P less than 0.05) during exercise at high altitude. alpha-ANF was not affected by hypoxia. When beta-blockade was achieved at high altitude, exercise-induced elevation in PRA was completely abolished, but no additional decline in PA occurred. Plasma norepinephrine and epinephrine concentrations tended to be lower during maximal exercise at altitude; however, these differences were not statistically significant. Our results provide further evidence that hypoxia has a suppressive effect on the renin-aldosterone system. However, beta-adrenergic mechanisms do not appear to be responsible for inhibition of renin secretion at high altitude.     

Exercise training prevents decline in stroke volume during exercise in young healthy subjects.

Stroke volume (SV) increases above the resting level during exercise and then declines at higher intensities of exercise in sedentary subjects. The purpose of this study was to determine whether an attenuation of the decline in SV at higher exercise intensities contributes to the increase in maximal cardiac output (Qmax) that occurs in response to endurance training. We studied six men and six women, 25 +/- 1 (SE) yr old, before and after 12 wk of endurance training (3 days/wk running for 40 min, 3 days/wk interval training). Cardiac output was measured at rest and during exercise at 50 and 100% of maximal O2 uptake (Vo2max) by the C2H2-rebreathing method. VO2max was increased by 19% (from 2.7 +/- 0.2 to 3.2 +/- 0.3 l/min, P less than 0.001) in response to the training program. Qmax was increased by 12% (from 18.1 +/- 1 to 20.2 +/- 1 l/min, P less than 0.01), SV at maximal exercise was increased by 16% (from 97 +/- 6 to 113 +/- 8 ml/beat, P less than 0.001) and maximal heart rate was decreased by 3% (from 185 +/- 2 to 180 +/- 2 beats/min, P less than 0.01) after training. The calculated arteriovenous O2 content difference at maximal exercise was increased by 7% (14.4 +/- 0.4 to 15.4 +/- 0.4 ml O2/100 ml blood) after training. Before training, SV at VO2max was 9% lower than during exercise at 50% VO2max (P less than 0.05). In contrast, after training, the decline in SV between 50 and 100% VO2max was only 2% (P = NS). Furthermore, SV was significantly higher (P less than 0.01) at 50% VO2max after training than it was before. Left ventricular hypertrophy was evident, as determined by two-dimensional echocardiography at the completion of training. The results indicate that in young healthy subjects the training-induced increase in Qmax is due in part to attenuation of the decrease in SV as exercise intensity is increased.     

Attenuated hepatosplanchnic uptake of lactate during intense exercise in humans.

We evaluated whether the increase in blood lactate with intense exercise is influenced by a low hepatosplanchnic blood flow as assessed by indocyanine green dye elimination and blood sampling from an artery and the hepatic vein in eight men. The hepatosplanchnic blood flow decreased from a resting value of 1.6 +/- 0.1 to 0.7 +/- 0.1 (SE) l/min during exercise. Yet the hepatosplanchnic O2 uptake increased from 67 +/- 3 to 93 +/- 13 ml/min, and the output of glucose increased from 1.1 +/- 0.1 to 2.1 +/- 0.3 mmol/min (P < 0.05). Even at the lowest hepatosplanchnic venous hemoglobin O2 saturation during exercise of 6%, the average concentration of glucose in arterial blood was maintained close to the resting level (5.2 +/- 0.2 vs. 5.5 +/- 0.2 mmol/l), whereas the difference between arterial and hepatic venous blood glucose increased to a maximum of 22 mmol/l. In arterial blood, the concentration of lactate increased from 1.1 +/- 0.2 to 6.0 +/- 1.0 mmol/l, and the hepatosplanchnic uptake of lactate was elevated from 0.4 +/- 0.06 to 1.0 +/- 0.05 mmol/min during exercise (P < 0.05). However, when the hepatosplanchnic venous hemoglobin O2 saturation became low, the arterial and hepatosplanchnic venous blood lactate difference approached zero. Even with a marked reduction in its blood flow, exercise did not challenge the ability of the liver to maintain blood glucose homeostasis. However, it appeared that the contribution of the Cori cycle decreased, and the accumulation of lactate in blood became influenced by the reduced hepatosplanchnic blood flow.     

Reflex cardiovascular and ventilatory responses to increasing H+ activity in cat hindlimb muscle

Static exercise increases arterial pressure, heart rate, and ventilation, effects which are believed in part to arise reflexly from a metabolic stimulus in the working muscle. In anesthetized cats, we tested the hypothesis that intra-arterial injections of lactic and hydrochloric acid, which created levels of these substances in muscle similar to those seen during contraction, reflexly increased cardiovascular and ventilatory function. Hydrochloric acid (32 and 57 mM; 1 ml) injected into the arterial supply of the triceps surae decreased intramuscular pH from 7.26 +/- 0.05 to 7.17 +/- 0.05 (P less than 0.01) and reflexly increased arterial pressure (23 +/- 7 mmHg; P less than 0.01), heart rate (11 +/- 2 beats/min; P less than 0.001), and ventilation (187 +/- 72 ml/min; P less than 0.05). Static contraction of the triceps surae decreased intramuscular pH from 7.28 +/- 0.06 to 7.13 +/- 0.06 (P less than 0.01). Lactic acid was more potent in causing reflexes than was equimolar HCl. For example, lactic acid containing 4 mM lactate and 0.87 mM H+ reflexly increased arterial pressure, heart rate, and ventilation, whereas 0.87 mM HCl did not. Intra-arterial sodium lactate (13 and 33 mM) at a neutral pH had no effect on these variables. We conclude that contraction-induced accumulation of H+, especially that arising from lactic acid, might provide a metabolic stimulus to evoke reflex autonomic effects.     

Changes in the tumor marker concentration in female patients with hyper-, eu-, and hypothyroidism

The levels of 6 circulating tumor markers were evaluated in a total of 131 female subjects with altered thyroid states; 36 normal subjects, 46 hyperthyroid patients with Graves' disease, and 49 primary hypothyroid patients. The mean CEA concentration was observed to be significantly higher (p less than 0.02) in hypothyroid patients than in normal and hyperthyroid patients (1.1 +/- 0.1 ng/ml, 0.8 +/- 0.1 ng/ml and 0.8 +/- 0.1 ng/ml, respectively). Similarly, the mean serum CA 125 concentration in hypothyroid patients was higher (p less than 0.02) than in normal and hyperthyroid patients (13.0 +/- 2.6 U/ml, 7.6 +/- 1.1 U/ml and 5.5 +/- 0.8 U/ml, respectively), and the mean serum CA 15-3 concentration in hypothyroid patients was significantly higher than in normal subjects (p less than 0.01) and hyperthyroid patients (p less than 0.001) (16.2 +/- 0.9 U/ml, 13.9 +/- 0.6 U/ml and 10.6 +/- 0.5 U/ml, respectively). No statistical difference was found in mean CA 19-9 in the three subject groups. AFP in the hypothyroid patients (3.6 +/- 0.3 ng/ml) was significantly higher (p less than 0.05) than in normal subjects (2.6 +/- 0.2 ng/ml) and hyperthyroid patients (1.7 +/- 0.2 ng/ml) (p less than 0.01). On the other hand, serum ferritin was low in the hypothyroid patients (65.9 8.0 ng/ml) and significantly increased (69.1 +/- 9.0 ng/ml) (p less than 0.02) with the normalization of thyroid function. In hyperthyroidism, serum ferritin (70.2 +/- 7.0 ng/ml) was significantly higher than in the hypothyroid patients (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversal of fatigue during prolonged exercise by carbohydrate infusion or ingestion

Seven cyclists exercised at 70% of maximal O2 uptake (VO2max) until fatigue (170 +/- 9 min) on three occasions, 1 wk apart. During these trials, plasma glucose declined from 5.0 +/- 0.1 to 3.1 +/- 0.1 mM (P less than 0.001) and respiratory exchange ratio (R) fell from 0.87 +/- 0.01 to 0.81 +/- 0.01 (P less than 0.001). After resting 20 min the subjects attempted to continue exercise either 1) after ingesting a placebo, 2) after ingesting glucose polymers (3 g/kg), or 3) when glucose was infused intravenously ("euglycemic clamp"). Placebo ingestion did not restore euglycemia or R. Plasma glucose increased (P less than 0.001) initially to approximately 5 mM and R rose (P less than 0.001) to approximately 0.83 with glucose infusion or carbohydrate ingestion. Plasma glucose and R then fell gradually to 3.9 +/- 0.3 mM and 0.81 +/- 0.01, respectively, after carbohydrate ingestion but were maintained at 5.1 +/- 0.1 mM and 0.83 +/- 0.01, respectively, by glucose infusion. Time to fatigue during this second exercise bout was significantly longer during the carbohydrate ingestion (26 +/- 4 min; P less than 0.05) or glucose infusion (43 +/- 5 min; P less than 0.01) trials compared with the placebo trial (10 +/- 1 min). Plasma insulin (approximately 10 microU/ml) and vastus lateralis muscle glycogen (approximately 40 mmol glucosyl U/kg) did not change during glucose infusion, with three-fourths of total carbohydrate oxidation during the second exercise bout accounted for by the euglycemic glucose infusion rate (1.13 +/- 0.08 g/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute anemia increases lactate production and decreases clearance during exercise

We evaluated whether elevated blood lactate concentration during exercise in anemia is the result of elevated production or reduced clearance. Female Sprague-Dawley rats were made acutely anemic by exchange transfusion of plasma for whole blood. Hemoglobin and hematocrit were reduced 33%, to 8.6 +/- 0.4 mg/dl and 26.5 +/- 1.1%, respectively. Blood lactate kinetics were studied by primed continuous infusion of [U-14C]lactate. Blood flow distribution during rest and exercise was determined from injection of 153Gd- and 113Sn-labeled microspheres. Resting blood glucose (5.1 +/- 0.2 mM) and lactate (1.9 +/- 0.02 mM) concentrations were not different in anemic animals. However, during exercise blood glucose was lower in anemic animals (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and lactate was higher (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM). Blood lactate disposal rates (turnover measured with recyclable tracer, Ri) were not different at rest and averaged 136 +/- 5.8 mumol.kg-1.min-1. Ri was significantly elevated in both control (260.9 +/- 7.1 mumol.kg-1.min-1) and anemic animals (372.6 +/- 8.6) during exercise. Metabolic clearance rate (MCR = Ri/[lactate]) did not differ during rest (151 +/- 8.2 ml.kg-1.min-1); MCR was reduced more by exercise in anemic animals (64.3 +/- 3.8) than in controls (129.2 +/- 4.1). Plasma catecholamine levels were not different in resting rats, with pooled mean values of 0.45 +/- 0.1 and 0.48 +/- 0.1 ng/ml for epinephrine (E) and norepinephrine (NE), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Catecholamine response is attenuated during moderate-intensity exercise in response to the "lactate clamp"

Catecholamine release is known to be regulated by feedforward and feedback mechanisms. Norepinephrine (NE) and epinephrine (Epi) concentrations rise in response to stresses, such as exercise, that challenge blood glucose homeostasis. The purpose of this study was to assess the hypothesis that the lactate anion is involved in feedback control of catecholamine concentration. Six healthy active men (26 +/- 2 yr, 82 +/- 2 kg, 50.7 +/- 2.1 ml.kg(-1).min(-1)) were studied on five occasions after an overnight fast. Plasma concentrations of NE and Epi were determined during 90 min of rest and 90 min of exercise at 55% of peak O2 consumption (VO2 peak) two times with exogenous lactate infusion (lactate clamp, LC) and two times without LC (CON). The blood lactate profile ( approximately 4 mM) of a preliminary trial at 65% VO2 peak (65%) was matched during the subsequent LC trials. In resting men, plasma NE concentration was not different between trials, but during exercise all conditions were different with 65% > CON > LC (65%: 2,115 +/- 166 pg/ml, CON: 1,573 +/- 153 pg/ml, LC: 930 +/- 174 pg/ml, P < 0.05). Plasma Epi concentrations at rest were different between conditions, with LC less than 65% and CON (65%: 68 +/- 9 pg/ml, CON: 59 +/- 7 pg/ml, LC: 38 +/- 10 pg/ml, P < 0.05). During exercise, Epi concentration showed the same trend (65%: 262 +/- 37 pg/ml, CON: 190 +/- 34 pg/ml, LC: 113.2 +/- 23 pg/ml, P < 0.05). In conclusion, lactate attenuates the catecholamine response during moderate-intensity exercise, likely by feedback inhibition.