Effect of dopamine on transient ventilatory response to exercise

The effect of exogenous dopamine on the development of exercise hyperpnea was studied. Using a bicycle ergometer, five subjects performed repetitive square-wave work-load testing from unloaded pedaling to 80% of each subject's estimated anaerobic threshold. The breath-by-breath ventilation (VE), CO2 production (VCO2), and O2 consumption (VO2) responses were analyzed by curve fitting a first-order exponential model. Comparisons were made between control experiments and experiments with a 3-micrograms X kg-1 X min-1 intravenous infusion of dopamine. Steady-state VE, VCO2 and VO2 were unchanged by the dopamine infusion, both during unloaded pedaling and at the heavier work load. The time constants for the increase in VE (tau VE) and VCO2 (tau CO2) were significantly (P less than 0.05) slowed (tau VE = 56.5 +/- 16.4 s for control, and tau VE = 76.4 +/- 26.6 s for dopamine; tau CO2 = 51.5 +/- 10.6 s for control, and tau CO2 = 64.8 +/- 17.4 s for dopamine) (mean +/- SD), but the time constant for VO2 (tau O2) was not significantly affected (tau O2 = 27.5 +/- 11.7 s for control, and tau O2 = 31.0 +/- 10.1 s for dopamine). We conclude that ablation of carotid body chemosensitivity with dopamine slows the transient ventilatory response to exercise while leaving the steady-state response unaffected.     

Effect of chronic pulmonary denervation on ventilatory responses to exercise

To assess the role of intrapulmonary receptors on the ventilatory responses to exercise we studied six beagle dogs before and after chronic pulmonary denervation and five dogs before and after sham thoracotomies. Each exercise challenge consisted of 6 min of treadmill exercise with measurements taken during the third minute at 3.2 km/h, 0% grade, and during the third minute at 5.0 km/h, 0% grade. Inspiratory and expiratory airflows were monitored with a low-dead-space latex mask and pneumotachographs coupled to differential pressure transducers. Both pre- and postsurgery, all dogs exhibited a significant arterial hypocapnia and alkalosis during exercise. Denervation of the lungs had no significant effect on minute ventilation at rest or during exercise, although there was a lower frequency and higher tidal volume in the lung-denervated dogs at all measurement periods. Breathing frequency increased significantly during exercise in lung-denervated dogs but to a lesser magnitude than in the control dogs. The changes that occurred in breathing frequency in all animals were due predominantly to the shortening of expiratory time. Inspiratory time did not shorten significantly during exercise following lung denervation. We conclude from these data that intrapulmonary receptors which are deafferented by sectioning the vagi at the hilum are not responsible for setting the level of ventilation during rest or exercise but are involved in determining the pattern of breathing.     

Effect of glycogen depletion on the ventilatory response to exercise

Five male subjects performed two graded exercise studies, one during control conditions and the other after reduction of muscle glycogen content by repeated maximum exercise and a high fat-protein diet. Reduction in preexercise muscle glycogen from 59.1 to 17.1 mumol X g-1 (n = 3) was associated with a 14% reduction in maximum power output but no change in maximum O2 intake; at any given power output O2 intake, heart rate, and ventilation (VE) were significantly higher, CO2 output (VCO2) was similar, and the respiratory exchange ratio was lower during glycogen depletion compared with control. The higher VE during glycogen depletion was associated with a higher VE/VCO2 ratio, lower end-tidal and mixed venous CO2 partial pressures, and higher blood pH than in the control studies. Changes in exercise VE accompanying glycogen depletion were not explained by changes in CO2 flux to the lungs suggesting that other factors served to modulate VE in these experimental conditions.     

Effect of aging on ventilatory response to exercise and CO2

Studies were performed to determine the effects of aging on the ventilatory responsiveness to two known respiratory stimulants, inhaled CO2 and exercise. Although explanation of the physiological mechanisms underlying development of exercise hyperpnea remains elusive, there is much circumstantial evidence that during exercise, however mediated, ventilation is coupled to CO2 production. Thus matched groups of young and elderly subjects were studied to determine the relationship between increasing ventilation and increasing CO2 production (VCO2) during steady-state exercise and the change in their minute ventilation in response to progressive hypercapnia during CO2 rebreathing. We found that the slope of the ventilatory response to hypercapnia was depressed in elderly subjects when compared with the younger control group (delta VE/delta PCO2 = 1.64 +/- 0.21 vs. 2.44 +/- 0.40 l X min-1 X mmHg-1, means +/- SE, respectively). In contrast, the slope of the relationship between ventilation and CO2 production during exercise in the elderly was greater than that of younger subjects (delta VE/delta VCO2 = 29.7 +/- 1.19 vs. 25.3 +/- 1.54, means +/- SE, respectively), as was minute ventilation at a single work load (50 W) (32.4 +/- 2.3 vs. 25.7 +/- 1.54 l/min, means +/- SE, respectively). This increased ventilation during exercise in the elderly was not produced by arterial O2 desaturation, and increased anaerobiasis did not play a role. Instead, the increased ventilation during exercise seems to compensate for increased inefficiency of gas exchange such that exercise remains essentially isocapnic. In conclusion, in the elderly the ventilatory response to hypercapnia is less than in young subjects, whereas the ventilatory response to exercise is greater.     

Effect of elastic loading on ventilatory pattern during progressive exercise

Ventilatory responses to progressive exercise, with and without an inspiratory elastic load (14.0 cmH2O/l), were measured in eight healthy subjects. Mean values for unloaded ventilatory responses were 24.41 +/- 1.35 (SE) l/l CO2 and 22.17 +/- 1.07 l/l O2 and for loaded responses were 24.15 +/- 1.93 l/l CO2 and 20.41 +/- 1.66 l/l O2 (P greater than 0.10, loaded vs. unloaded). At levels of exercise up to 80% of maximum O2 consumption (VO2max), minute ventilation (VE) during inspiratory elastic loading was associated with smaller tidal volume (mean change = 0.74 +/- 0.06 ml; P less than 0.05) and higher breathing frequency (mean increase = 10.2 +/- 0.98 breaths/min; P less than 0.05). At levels of exercise greater than 80% of VO2max and at exhaustion, VE was decreased significantly by the elastic load (P less than 0.05). Increases in respiratory rate at these levels of exercise were inadequate to maintain VE at control levels. The reduction in VE at exhaustion was accompanied by significant decreases in O2 consumption and CO2 production. The changes in ventilatory pattern during extrinsic elastic loading support the notion that, in patients with fibrotic lung disease, mechanical factors may play a role in determining ventilatory pattern.     

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P < 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P < 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P < 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise.     

Effect of endurance exercise training on ventilatory function in older individuals

To evaluate the effect of endurance training on ventilatory function in older individuals, 1) 14 master athletes (MA) [age 63 +/- 2 yr (mean +/- SD); maximum O2 uptake (VO2max) 52.1 +/- 7.9 ml . kg-1 . min-1] were compared with 14 healthy male sedentary controls (CON) (age 63 +/- 3 yr; VO2max of 27.6 +/- 3.4 ml . kg-1 . min-1), and 2) 11 sedentary healthy men and women, age 63 +/- 2 yr, were reevaluated after 12 mo of endurance training that increased their VO2max 25%. MA had a significantly lower ventilatory response to submaximal exercise at the same O2 uptake (VE/VO2) and greater maximal voluntary ventilation (MVV), maximal exercise ventilation (VEmax), and ratio of VEmax to MVV than CON. Except for MVV, all of these parameters improved significantly in the previously sedentary subjects in response to training. Hypercapnic ventilatory response (HCVR) at rest and the ventilatory equivalent for CO2 (VE/VCO2) during submaximal exercise were similar for MA and CON and unaffected by training. We conclude that the increase in VE/VO2 during submaximal exercise observed with aging can be reversed by endurance training, and that after training, previously sedentary older individuals breathe at the same percentage of MVV during maximal exercise as highly trained athletes of similar age.     

Effect of menstrual cycle phase on the ventilatory response to rising body temperature during exercise

To examine the effect of menstrual cycle on the ventilatory sensitivity to rising body temperature, ten healthy women exercised for ~60 min on a cycle ergometer at 50% of peak oxygen uptake during the follicular and luteal phases of their cycle. Esophageal temperature, mean skin temperature, mean body temperature, minute ventilation, and tidal volume were all significantly higher at baseline and during exercise in the luteal phase than the follicular phase. On the other hand, end-tidal partial pressure of carbon dioxide was significantly lower during exercise in the luteal phase than the follicular phase. Plotting ventilatory parameters against esophageal temperature revealed there to be no significant menstrual cycle-related differences in the slopes or intercepts of the regression lines, although minute ventilation and tidal volume did significantly differ during exercise with mild hyperthermia. To evaluate the cutaneous vasodilatory response, relative laser-Doppler flowmetry values were plotted against mean body temperature, which revealed that the mean body temperature threshold for cutaneous vasodilation was significantly higher in the luteal phase than the follicular phase, but there were no significant differences in the sensitivity or peak values. These results suggest that the menstrual cycle phase influences the cutaneous vasodilatory response during exercise and the ventilatory response at rest and during exercise with mild hyperthermia, but it does not influence ventilatory responses during exercise with moderate hyperthermia.     

Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans

The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/- 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT.