Pseudoephedrine is without ergogenic effects during prolonged exercise

Gillies, Hunter, Wayne E. Derman, Timothy D. Noakes, Peter Smith, Alicia Evans, and Gary Gabriels.Pseudoephedrine is without ergogenic effects during prolongedexercise. J. Appl. Physiol. 81(6): 2611-2617, 1996.This study was designed to measure whether a single dose of 120 mg pseudoephedrine ingested 120 min before exercise influencesperformance during 1 h of high-intensity exercise. The effects ofexercise on urinary excretion of the drug were also studied. Tenhealthy male cyclists were tested on two occasions, separated by atleast 7 days, by using a randomly assigned, double-blind,placebo-controlled, crossover design. Exercise performance was testedduring a 40-km trial on a laboratory cycle ergometer, and skeletalmuscle function was measured during isometric contractions. On a thirdoccasion, subjects ingested 120 mg pseudoephedrine but did not exercise[control (C)]. Pseudoephedrine did not influence eithertime trial performance [drug (D) vs. placebo: 58.1 ± 1.4 (SE) vs. 58.7 ± 1.5 min] or isometric muscle function. Urinary pseudoephedrine concentrations were significantly increased 1 h after exercise (D vs. C: 114.3 ± 27.2 vs. 35.4 ± 13.1 µg/ml; P < 0.05). Peak plasma pseudoephedrineconcentrations (P < 0.05) but not time taken to reach peakplasma concentrations or the area under the plasma pseudoephedrineconcentration vs. time curve was significantly increased in the totalgroup with exercise (D vs. C). In three subjects, plasmapseudoephedrine concentrations were not influenced by exercise. Onlythese subjects showed increased urinary pseudoephedrine excretionduring exercise. We conclude that a single therapeutic dose ofpseudoephedrine did not have a measurable ergogenic effect duringhigh-intensity exercise of 1-h duration, but plasma drug concentrationsand urinary excretion were altered by exercise. These findings havepractical relevance to doping control regulations in internationalsporting competitions.

     

Baroreflex responsiveness is maintained during isometric exercise in humans

The simultaneous rise in heart rate and arterial pressure during isometric handgrip exercise suggests that arterial baroreflex control may be altered. We applied incremental intensities of neck suction and pressure to nine healthy young men to alter carotid sinus transmural pressure. Carotid stimuli were delivered during 1) supine control, 2) "anticipation" of beginning exercise, and 3) handgrip (20% of maximum voluntary contraction). Anticipation was a quiet period, immediately preceding the beginning of handgrip, when no muscular work was being performed. Compared with control, the R-R interval prolongation and mean arterial pressure decline provoked by carotid stimuli were decreased during the anticipation period. These data suggest that influences from higher central neural locations may alter baroreflex function. Furthermore, we derived stimulus-response curves relating carotid sinus transmural pressure to changes in R-R interval and mean arterial pressure. These curves were shifted during handgrip; however, calculated regression slopes were not changed from control. The data indicate that isometric handgrip exercise has a specific influence on human carotid baroreflex control of arterial pressure and heart period: baroreflex function curves are shifted rightward during handgrip, whereas baroreflex sensitivity is unchanged. Furthermore, central neural influences may be partially involved in these alterations.     

Carotid baroreflex function during prolonged exercise.

The present investigation was designed to uncouple the hemodynamic physiological effects of thermoregulation from the effects of a progressively increasing central command activation during prolonged exercise. Subjects performed two 1-h bouts of leg cycling exercise with 1) no intervention and 2) continuous infusion of a dextran solution to maintain central venous pressure constant at the 10-min pressure. Volume infusion resulted in a significant reduction in the decrement in mean arterial pressure seen in the control exercise bout (6.7 +/- 1.8 vs. 11.6+/- 1.3 mmHg, respectively). However, indexes of central command such as heart rate and ratings of perceived exertion rose to a similar extent during both exercise conditions. In addition, the carotid-cardiac baroreflex stimulus-response relationship, as measured by using the neck pressure-neck suction technique, was reset from rest to 10 min of exercise and was further reset from 10 to 50 min of exercise in both exercise conditions, with the operating point being shifted toward the reflex threshold. We conclude that the progressive resetting of the carotid baroreflex and the shift of the reflex operating point render the carotid-cardiac reflex ineffectual in counteracting the continued decrement in mean arterial pressure that occurs during the prolonged exercise.     

Variation of cardiac cycle during prolonged cycling exercise

The purpose of this study was to elucidate the changes in heart rate (HR), systolic and diastolic time intervals accompanying prolonged cycling exercise. Seven healthy male students (N group) and seven male collegiate long distance runners (LDR group) underwent 60-min bicycle ergometer exercise loaded at 30% and 50% HRmax. Electrocardiogram (ECG) and phonocardiogram (PCG) were recorded throughout the exercise and recovery period, and then left ventricular ejection time (LVET) and left ventricular diastolic time (LVDT) were calculated from tracings of the cardiac cycle. In the N group, HR increased to the target HR level (30% and 50% HRmax) in the initial phase of exercise, but there was a tendency to increase 10-15 b/min in the latter half of the exercise period. The LDR group showed the same trend as in the N group at 50% HRmax level (i.e., 120 b/min) exercise. These increments of the HR were due to the decrease of stroke volume, the elevation of body temperature and changes in the volume of the venous return. In the initial phase of exercise (within five minutes), LVDT decreased markedly resulting in a rapid increase of the HR in both groups. The decrease in LVDT was 250-400 msec (60-70% decrement for resting value) at the 30% HRmax level load and 270-480 msec (73-80% decrement for resting value) at the 50% HRmax level load, and then transient slight increment was recognized. Subsequently, there was a tendency to decrease. The major factor for the increase of the HR was that the LVDT decreased markedly that implied the shortening of the inflow time to the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of blood glucose homeostasis during prolonged exercise

The maintenance of normal blood glucose levels at rest and during exercise is critical. The maintenance of blood glucose homeostasis depends on the coordination and integration of several physiological systems, including the sympathetic nervous system and the endocrine system. During prolonged exercise increased demand for glucose by contracting muscle causes to increase glucose uptake to working skeletal muscle. Increase in glucose uptake by working skeletal muscle during prolonged exercise is due to an increase in the translocation of insulin and contraction sensitive glucose transporter-4 (GLUT4) proteins to the plasma membrane. However, normal blood glucose level can be maintained by the augmentation of glucose production and release through the stimulation of liver glycogen breakdown, and the stimulation of the synthesis of glucose from other substances, and by the mobilization of other fuels that may serve as alternatives. Both feedback and feedforward mechanisms allow glycemia to be controlled during exercise. This review focuses on factors that control blood glucose homeostasis during prolonged exercise.     

Muscle energetics during prolonged cycling after exercise hypervolemia

This study examined the question of whether increases in plasma volume (hypervolemia) induced through exercise affect muscle substrate utilization and muscle bioenergetics during prolonged heavy effort. Six untrained males (19-24 yr) were studied before and after 3 consecutive days of cycling (2 h/day at 65% of peak O2 consumption) performed in a cool environment (22-23 degrees C, 25-35% relative humidity). This protocol resulted in a 21.2% increase in plasma volume (P less than 0.05). During exercise no difference was found in the blood concentrations of glucose, lactate, and plasma free fatty acids at either 30, 60, 90, or 120 min of exercise before and after the hypervolemia. In contrast, blood alanine was higher (P less than 0.05) during both rest and exercise with hypervolemia. Measurement of muscle samples extracted by biopsy from the vastus lateralis muscle at rest and at 60 and 120 min of exercise indicated no effect of training on high-energy phosphate metabolism (ATP, ADP, creatine phosphate, creatine) or on selected glycolytic intermediate concentrations (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, lactate). In contrast, training resulted in higher (P less than 0.05) muscle glucose and muscle glycogen concentrations. These changes were accompanied by blunting of the exercise-induced increase (P less than 0.05) in both blood epinephrine and norepinephrine concentrations. Plasma glucagon and serum insulin were not affected by the training. The results indicate that exercise-induced hypervolemia did not alter muscle energy homeostasis. The reduction in muscle glycogen utilization appears to be an early adaptive response to training mediated either by an increase in blood glucose utilization or a decrease in anaerobic glycolysis.     

Muscle metabolism during prolonged physical exercise in dogs

In order to provide reference data, adenine nucleotide, creatine phosphate, glycogen, glycolytic intermediates and lactate muscle contents were measured in 49 dogs under resting conditions and during prolonged physical exercise of moderate intensity performed until exhaustion. Both the resting and exercise values of the measured variables were remarkably similar to those described in human subjects, except muscle lactate content which achieved higher values during submaximal exercise in dogs than in men.     

Neurohumoral responses during prolonged exercise in humans.

This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 +/- 0.1 degrees C (mean +/- SE) in the control trial, whereas it increased to 39.7 +/- 0.2 degrees C in the hyperthermic trial, with a concomitant increase in perceived exertion (P < 0.05). At rest, the brain had a small release of tryptophan (arteriovenous difference of -1.2 +/- 0.3 micromol/l), whereas a net balance was obtained during the two exercise trials. Both the arterial and jugular venous dopamine levels became elevated during the hyperthermic trial, but the net release from the brain was unchanged. During exercise, the O2/CHO was similar across trials, but, during recovery from the hyperthermic trial, the ratio decreased to 3.8 +/- 0.3 (P < 0.05), whereas it returned to the baseline level of approximately 6 within 5 min after the control trial. The lowering of O2/CHO was established by an increased arteriovenous glucose difference (1.1 +/- 0.1 mmol/l during recovery from hyperthermia vs. 0.7 +/- 0.1 mmol/l in control; P < 0.05). The present findings indicate that the brain has an increased need for carbohydrates during recovery from strenuous exercise, whereas enhanced perception of effort as observed during exercise with hyperthermia was not related to alterations in the cerebral balances of dopamine or tryptophan.     

Stroke volume decline during prolonged exercise is influenced by the increase in heart rate.

This study determined whether the decline in stroke volume (SV) during prolonged exercise is related to an increase in heart rate (HR) and/or an increase in cutaneous blood flow (CBF). Seven active men cycled for 60 min at approximately 57% peak O2 uptake in a neutral environment (i.e., 27 degrees C, <40% relative humidity). They received a placebo control (CON) or a small oral dose (i.e., approximately 7 mg) of the beta1-adrenoceptor blocker atenolol (BB) at the onset of exercise. At 15 min, HR and SV were similar during CON and BB. From 15 to 55 min during CON, a 13% decline in SV was associated with an 11% increase in HR and not with an increase in CBF. CBF increased mainly from 5 to 15 min and remained stable from 20 to 60 min of exercise in both treatments. However, from 15 to 55 min during BB, when the increase in HR was prevented by atenolol, the decline in SV was also prevented, despite a normal CBF response (i.e., similar to CON). Cardiac output was similar in both treatments and stable throughout the exercise bouts. We conclude that during prolonged exercise in a neutral environment the decline in SV is related to the increase in HR and is not affected by CBF.     

Sex differences in left ventricular function and beta-receptor responsiveness following prolonged strenuous exercise.

Sex differences in neuroendocrine and metabolic responses to prolonged strenuous exercise (PSE) have been well documented. The aim of this investigation was to examine sex differences in left ventricular function and cardiac beta-receptor responsiveness following a single bout of PSE. Nine male and eight female triathletes were examined during three separate sessions: before, immediately after, and 24 h following a half-ironman triathlon using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess beta-receptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each participant were used as an index of beta-receptor responsiveness. Despite no change in preload, fractional area change decreased from baseline after the race in both men and women, with a greater decrease in men [men: 54.1% (SD 2.1) to 50.7% (SD 3.4) vs. women: 55.4% (SD 2.7) to 53.3% (SD 2.5); P < 0.05]. The amount of dobutamine necessary to increase heart rate by 25 beats/min [men: 29.6 microg x kg(-1) x min(-1) (SD 6.6) to 42.7 microg x kg(-1) x min(-1) (SD 12.9) vs. women: 23.5 microg x kg(-1) x min(-1) (SD 4.0) to 30.0 microg x kg(-1) x min(-1) (SD 7.8); P < 0.05] and contractility by 10 mmHg/cm2 [men: 20.9 microg x kg(-1) x min(-1) (SD 5.1) to 37.0 microg x kg(-1) x min(-1) (SD 11.5) vs. women: 22.6 microg x kg(-1) x min(-1) (SD 6.4) to 30.7 microg x kg(-1) x min(-1) (SD 7.2); P < 0.05] was greater in both men and women postrace. However, the amount of dobutamine required to induce these changes was greater in men, reflecting larger beta-receptor alterations in male triathletes following PSE relative to women. These data suggest that following an acute bout of PSE, male triathletes demonstrate an attenuated chronotropic and inotropic response to beta-adrenergic stimulation compared with female triathletes.     

Substrate usage during prolonged exercise following a preexercise meal

The effect of a high-carbohydrate meal 4 h before 105 min of exercise at 70% of maximal O2 uptake was determined in seven endurance-trained cyclists and compared with exercise following a 16-h fast. The preexercise meal produced a transient elevation of plasma insulin and blood glucose, which returned to fasting basal levels prior to the initiation of exercise. The meal also resulted in a 42% elevation (P less than 0.05) of glycogen within the vastus lateralis at the beginning of exercise. The 1st h of exercise when subjects were fed was characterized by a 13-25% decline (P less than 0.05) in blood glucose concentration, a suppression of the normal increase in plasma free fatty acids and blood glycerol, and a 45% (P less than 0.05) greater rate of carbohydrate oxidation compared with exercise when subjects were fasted. After 105 min of exercise, there were no significant differences when subjects were fed or fasted regarding blood glucose levels, rate of carbohydrate oxidation, or muscle glycogen concentration. The greater muscle glycogen utilization (97 +/- 18 vs. 64 +/- 8 mmol glucosyl units X kg-1; P less than 0.05) and carbohydrate oxidation when subjects were fed appeared to be derived from the glycogen synthesized following the meal. These results indicate that preexercise feedings alter substrate availability despite a return of plasma insulin to fasting levels prior to exercise and that these effects persist until the 2nd h of exercise.