Effects of beta-adrenergic blockade on ventilation and gas exchange during exercise in humans.

The effects of beta-adrenergic blockade induced by intravenous propranolol hydrochloride (0.2 mg/kg) on ventilatory and gas exchange responses to exercise were studied during tests in which the work rate was either increased progressively or maintained at a constant load in six healthy young male subjects. Heart rate during exercise decreased by about 20% and cardiac output, as estimated by a modification of the method of Kim et al. (J. Appl. Physiol. 21: 1338-1344, 1966), by about 15%. The relation between work rate and O2 uptake (VO2) was unaffected by propranolol, whereas maximal O2 uptake (VO2max) decreased by 5% and the anaerobic threshold, estimated noninvasively, was lowered by 23%. The relations between CO2 output (VCO2) and end-tidal CO2 partial pressure (PCO2) and between VCO2 and minute ventilation (VE) were both unaffected. The time constants for changes of VO2, VCO2, and VE during on-transients from unloaded pedaling to either a moderate (ca. 50% VO2max) or a heavy (ca. 67% VO2max) work rate in the control studies were in agreement with previously reported values, i.e., 42, 60, and 69 s, respectively. beta-Blockade was associated with a significantly increased time constant for VO2 of 61 s but with less consistent and insignificant changes for VCO2 and VE. There was a small but significant increase of the time constant for heart rate from 40 to 45 s. It is concluded that propranolol exerts its primary influence during exercise on the cardiovascular system without any discernible effect on ventilatory control.

Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction.

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.

Ventilatory control during experimental maldistribution of VA/Q in the dog.

To determine the role of the peripheral chemoreceptors in mediating the hyperpnea associated with acute, nonocclusive inflation of a balloon in the main pulmonary artery of the conscious dog, we performed balloon inflations in awake and lightly anesthetized (chloralose-urethan) dogs before and after a) bilateral carotid body resection (CBR), b) cervical vagotomy (V), and c) after both CBR and V. In the intact awake state, balloon inflation increased VE from a mean of 4.91 to 7.16 1/min, usually within 1.5-2.0 min. Mean arterial PO2 decreased from 82 to 71 Torr and end-tidal PCO2 was reduced by 6 Torr. Arterial PCO2 and pH were unchanged in the steady state (as evidenced by discrete blood samples), even in those dogs in which VE increased up to 7.5 1/min. However, an indwelling PCO2 electrode in the femoral artery demonstrated a consistent transient elevation of arterial PCO2 prior to the steady state regulation. Vagotomy alone did not impair the ability to regulate PCO2 during balloon inflation. In some cases with CBR alone, arterial PCO2 was regulated at control levels in the steady state, but the transient increase during the early phase of balloon inflation was more marked (mean increase, 2 Torr). We conclude that the peripheral chemoreceptors are responsible for a significant component of the dynamic ventilatory behavior during this early phase (1.5-2.0 min) of acute maldistribution of VA/Q.

Effect of ramp slope on determination of aerobic parameters from the ramp exercise test.

The effect of ramp slope on determination of aerobic parameters from the ramp exercise test. Med. Sci. Sports Exercise, Vol. 14, No. 5, pp. 339-343, 1982. We have previously demonstrated that the four parameters of aerobic function (maximal oxygen uptake (muVO2), VO2 at the anaerobic threshold (theta an), the time constant for VO2 kinetics (tau VO2), and work efficiency (eta)) may all be determined reliably from a single test in which the work rate increases continuously at a constant rate, i.e., ramp. That study, however, utilized a single ramp slope of 50 W X min-1, which may not be appropriate for subjects with very low or very high work tolerances. We therefore studied the effect of different ramp slopes on the determination of these parameters. Ramp slopes of 20, 30, 50, and 100 W X min-1 were generated on a cycle ergometer, and each was assigned randomly to 14 healthy subjects. Ventilatory and gas exchange variables were measured breath-by-breath utilizing on-line digital computation. Ramp slopes of 20, 30, and 50 W X min-1 yielded the same values for each aerobic parameter. The 100 W X min-1 ramp yielded muVO2 and eta an values that were the same as those found for the other ramp slopes, but tau VO2 and eta could not be discerned validly from this ramp slope. We conclude that valid assessment of the four parameters of aerobic function is possible with ramp slopes between 20 and 50 W X min-1; no further information on the parameters is to be gained by prolonging the tests with ramps slower than 20 W X min-1.

Role of neural afferents from working limbs in exercise hyperpnea.

To determine the role of reflex discharge of afferent nerves from the working limbs in the exercise hyperpnea, 1.5- to 2.5-min periods of phasic hindlimb muscle contraction were induced in anesthetized cats by bilateral electrical stimulation of ventral roots L7, S1, and S2. Expired minute ventilation (VE) and end-tidal PCO2 (PETCO2) were computed breath by breath, and mean arterial PCO2 (PaCO2) was determined from discrete blood samples and, also in most animals, by continuous measurement with an indwelling PCO2 electrode. During exercise VE rose progressively with a half time averaging approximately 30 s, but a large abrupt increase in breathing at exercise onset typically did not occur. Mean PaCO2 and PETCO2 remained within approximately 1 Torr of control levels across the work-exercise transition, and PaCO2 was regulated at an isocapnic level after VE had achieved its peak value. Sectioning the spinal cord at L1-L2 did not alter these response characteristics. Thus, reflex discharge of afferent nerves from the exercising limbs was not requisite for the matching of ventilation to metabolic demand during exercise.

Determinants of gas exchange kinetics during exercise in the dog.

Following exercise onset, CO2 output (VCO2) and O2 uptake (VO2) increase exponentially, but with appreciably different time constants. To determine the sensitivity of the time courses of these variables to altered ventilatory kinetics, rhythmic exercise was induced abruptly in anesthetized dogs by bilateral stimulation of the peripheral ends of the cut sciatic and femoral nerves. This increased the metabolic rate by 83 +/- 25 (SD) %. The dogs were ventilated with a constant-volume pump, the frequency of which was changed exponentially from the start of the exercise up to the ventilation that returned arterial CO2 and O2 pressure (PCO2 and PO2) in the steady state to resting levels. The time constant (tau) of the increase in ventilation (VE) was varied among trials. VCO2, VO2, end-tidal PCO2 and PO2, and arterial PCO2 were measured breath by breath. tauVO2 was constant at approximately 18 s regardless of alterations in tauVE. In contrast, tauVCO2 was strongly dependent on tauVE, apparently due to the larger body stores for CO2; the transitions were isocapnic when tau VE was approximately 40 s. We conclude that ventilatory dynamics can markedly influence the dynamics of CO2 exchange during exercise, but has no appreciable effect on O2 uptake dynamics.

Hypopnea consequent to reduced pulmonary blood flow in the dog.

The ventilatory responses to diminished pulmonary blood flow (Qc), as a result of partial cardiopulmonary bypass (PCB), were studied in chloralose-urethan-anesthetized dogs. Qc was reduced by diverting vena caval blood through a membrane gas exchanger and returning it to the ascending aorta. PCB flows of 400--1,600 ml/min were utilized for durations of 2--3 min. Decreasing Qc, while maintaining systemic arterial blood gases and perfusion, results in a significant (P less than 0.05) decrease in expiratory ventilation (VE) (15.9%) and alveolar ventilation (VA) (31.0%). The ventilatory decreases demonstrated for this intact group persist after bilateral cervical vagotomy (Vx), carotid body and carotid sinus denervation (Cx), and combined Vx and Cx. The changes in VE and VA were significantly (P less than 0.001) correlated with VCO2 changes, r = 0.80 and r = 0.93, respectively. These ventilatory changes were associated with an overall average decrease in left ventricular PCO2 of 2.1 Torr; this decrease was significant (P less than 0.05) only in the intact and Cx groups. Decreasing pulmonary blood flow results in a decrease in ventilation that may be CO2 related; however, the exact mechanism remains obscure but must have a component that is independent of vagally mediated cardiac and pulmonary afferents and peripheral baroreceptor and chemoreceptor afferents.

Ventilation and gas exchange during phasic hindlimb exercise in the dog.

To investigate the importance of the major neural afferent component from the exercising extremities in exercise hyperpnea, rhythmic contraction of hindlimb muscles was produced in the dog, by electrically stimulating the peripheral cut ends of the sciatic and femoral nerves, bilaterally, for 4- to 5-min periods. VE, VCO2, and VO2 were computed breath-by-breath and PaCO2 was monitored continuously with an indwelling arterial electrode. During exercise, VO2 and VCO2 were approximately doubled in the steady state, rising with t1/2 of 25 +/- 2 and 35 +/- 4 s, respectively. VE increased within five breaths after exercise onset, and thereafter rose to a steady state with a t1/2 of 37 +/- 5 s. Mean PaCO2 increased transiently within the 1st min of stimulation but was not significantly different from control in the steady state. We conclude that the major neural afferent component from the contracting muscles is not an obligatory requirement for normal ventilatory response in the steady state of phasic exercise.

Control of ventilation during intravenous CO2 loading in the awake dog.

The ventilatory response to venous CO2 loading and its effect on arterial CO2 tension was determined in five awake dogs. Blood, 200-500 ml/min, was diverted from a catheter in the right common carotid artery through a membrane gas exchanger and returned to the right jugular vein. CO2 loading was accomplished by changing the gas ventilating the gas exchanger from a mixture of 5% CO2 in air to 100% CO2. The ventilatory responses to this procedure were compared with those resulting from increased inspired CO2 concentrations (during which ventilation of the gas exchanger with the air and 5% CO2 mixture continued). The ventilatory response to each form of CO2 loading was computed as deltaVE/deltaPaco9. The mean ventilatory response to airway CO2 loading was 1.61 1/min per Torr PaCO2. The mean response for the venous CO2 loading was significantly higher and not significantly different from "infinite" CO2 sensitivity (i.e., isocapnic response). The results provide further evidence for a CO2-linked hyperpnea, not mediated by significant changes in mean arterial PCO2.

Regulation of arterial PCO2 during intravenous CO2 loading.

Increased CO2 flow to the lung produced by increasing cardiac output (with constant PVCO2) results in hyperpnea with arterial PCO2 maintained at its control value (J. Appl. Physiol. 36: 457, 1974). To study if arterial PCO2 could be similarly regulated when CO2 flow was elevated by increasing PVCO2 (without changing cardiac output), we produced graded increases in PVCO2 (up to a mean of 69 mmHg) using an extracorporeal gas exchanger in five chloralose-urethan-anesthetized dogs. CO2 output increased up to fourfold. Ventilation increased in proportion to the additional CO2 flow to the lung with consequent regulation of arterial PCO2 at its control value. Comparable increases in VE produced by "conventional" airway loading resulted in arterial hypercapnia. The resulting CO2 response curve was similar to that found in unanesthetized dogs. We conclude that intravenous delivery of CO2 to the lung results in infinite "sensitivity" when computed as Delta VE/Delta paco2. These results provide evidence for a CO2-linked hyperpnea which is not mediated by measurable increases in mean arterial PCO2.