Effect of exercise on lung-perfusion scanning in patients with bronchogenic carcinoma.

The aim of this study was to determine whether perfusion-scintillation scanning, used as a predictive pre-operative index of lung functionality in patients with lung cancer, is affected by the level of pulmonary blood flow (PBF). Twenty patients with primary lung cancer underwent spirometry and a radionuclide-perfusion scan (macroaggregated albumin particles labelled with 99mTechnetium) both at rest and during the last minute of a ramp-like increase in work rate until exhaustion. On average, the perfusion of the lung with the tumour was significantly reduced by the same magnitude at rest and during exercise (mean+/-SD: -9+/-6% versus -10+/-4% of the cardiac output), regardless of the extent of the tumour. However, subject-by-subject analysis revealed that in two patients, a larger decrease in the perfusion of the lung with the tumour was observed during exercise than at rest (-11% and -17%, respectively). This leads to an underestimation of predictive postoperative functional parameters if resting values are used in these patients. The use of perfusion scintigraphy at rest therefore gives a clear picture of the functionality of the lung before resection in most patients requiring surgery.

Control of breathing and muscle perfusion in humans.

Very brief and intense exercise triggers a biphasic metabolic and respiratory response with a second phase that occurs after the cessation of the muscular activity. The effects on minute ventilation (V(E)) produced by manipulation of the peripheral circulation in metabolically active muscles could thus be studied without the confounding effects of painful contractions. The second phase of breath-by-breath V(E) and pulmonary gas exchange responses to a brief change in work rate (400 W for 12 s) were studied in six healthy male subjects on four occasions (24 tests). An upper thigh cuff inflation was randomly applied either above or below the systolic blood pressure (200 or 90 Torr, respectively) for 90 s just after the cessation of the contractions prior to the delayed rise in pulmonary gas exchange (eight tests in each subject). Total occlusion produced a significant reduction in the delayed rise in V(E) (-29 +/- 3 %) which normally occurred 20-25 s after the cessation of the contractions. In contrast, cuff inflation at a level predominantly impeding venous return while partially maintaining the arterial supply reduced the rise in pulmonary gas exchange in similar proportion to that during total obstruction but with a slight but not significant reduction in ventilation (-9 +/- 5 %). V(E) during partial occlusion was if anything higher than in control tests with similar oxygen uptake (280 W), despite a higher blood pressure (BP) during occlusion (+7 Torr). It is concluded that the factors resulting from a reduction in venous return or from the involvement of the arterial baroreflex are not responsible for the changes in V(E) produced by the obstruction of the circulation to and from metabolically active muscles. It is proposed that factors related to the level of the perfusion pressure in hyperaemic muscles, possibly located at the venular end of the microcirculation, could account for the changes in V(E) observed.

Corticospinal pathway and exercise hyperpnea: lessons from a patient with Arnold Chiari malformation.

The study of a patient with an Arnold Chiari malformation gave us the opportunity to test the hypothesis that the motor cortex contributes significantly to respiratory control during muscular exercise through the corticospinal pathway. The patient was a 25 years old woman who exhibited a severe impairment of the 'automatic' ventilatory control due to a type I Arnold Chiari malformation. Since she never complained of being breathlessness even on exertion, the breath-by-breath ventilatory (VE) and pulmonary gas exchange responses to a three minute bout of constant work rate exercise at 60 W, 90 W and 120 W were studied before then 16 and 23 months after posterior fossa decompression. The VE response to the three different levels of exercise was dramatically blunted so that the expected vertical relationship between PET(CO(2)) and VE during moderate exercise was replaced by an almost horizontal relationship with a slope ranging from 0.15 to 0.17 l/min/Torr. The reduced VE response was associated with a total lack of respiratory sensation during and following the exercise bouts. This abnormal ventilatory response to exercise persisted despite posterior fossa decompression. There was however no evidence of an alteration of the corticospinal pathway. Indeed, not only was there no sign of motor deficit but the patient was able both to mobilize 96% of her expected vital capacity and to voluntarily increase her ventilation to the level expected in a normal subject during exercise. This observation suggests that during exercise, motor control of respiratory muscles via a direct corticospinal pathway does not play a major role in adjusting phrenic motoneuron activity to the magnitude of the motor inputs to the exercising skeletal muscles.

Stimulation of ventilation by normobaric hyperoxia in exercising dogs.

In order to describe the factors which, during hyperoxic exercise, can counteract the chemoreceptor-mediated inhibition of ventilation by O2, minute ventilation (VE) and the pulmonary gas exchange were studied breath-by-breath in four dogs running on a treadmill (5 km x h(-1)) for 10 min during and following exposure to O2 of different durations. We found that a brief inhalation of O2 applied during the steady state of the VE response provoked a reduction in VE by 6.5 +/- 0.9 l x min(-1) whereas hyperoxia applied 2 min before the onset of exercise and maintained for 2.5 min during the running tests had a significantly weaker effect on VE (-1.8 +/- 0.2 l x min(-1), P < 0.05). The rise in pulmonary CO2 output (VCO2) during the prolonged O2 exposure was less than in normoxic exercise leading to a deficit of CO2 eliminated by the lungs of 181 ml. The return to air breathing provoked a rise in VE, which reached within 73 s a much higher level than the control tests (22.9 +/- 3.6 vs. 19.5 +/- 2.2 l x min(-1), P < 0.05); VE then subsided to control levels with a long exponential decline. The CO2 deficit during O2 breathing, was fully compensated after recovery in air within 6 min. No stimulatory effect on ventilation was observed at rest at the cessation of a similar exposure to O2 despite a higher end-tidal PCO2 (+4 +/- 1 mmHg) than in exercise. In conclusion, the stimulatory effect of O2 during exercise can be clearly revealed after recovery in air and seems to operate through a more complex mechanism than that thought to be involved at rest. We propose that the changes in CO2 stores in the exercising muscles could contribute to O2-induced stimulation during exercise, possibly through stimulation of muscle afferents responding to local circulatory changes. Finally, the observation that during continuous dopamine (DA) infusion (5 microg x kg(-1) x min(-1)) the VE response to recovery in air was only a slow decrease, suggests that the arterial chemoreceptors potentiate O2-induced hyperventilation, or that the vascular actions of DA counteract part of the effects provoked by CO2 accumulation in the exercising muscles.

Heart rate dynamics during sinusoidal exercise: comparison of the control system between children and adults.

The aim was to model the dynamics of heart rate (HR) response to sinusoidal work rate (WR) forcing in children and adults. Seven pre-pubertal boys (aged 10-13) and five adult males (aged 22-37) were studied. Continuous ECG recordings were obtained during the following physiological manoeuvres: five constant amplitude ergometer exercises with WR varying sinusoidally with periods of 0.75, 1, 2, 3.5, and 5 min duration, and one step exercise at a constant WR equal to the midpoint of the sinusoid amplitude. The amplitude ratio (AR; standardized by WR) of the fundamental harmonic of the HR response and the phase shift (phi) between the WR to HR were calculated by Fourier analysis. The HR dynamic parameters (gain and time constant (tau)) of a first order model with or without delay (Td) were also estimated. The AR in children was always higher than that in adults, in absolute terms, but not as a function of body weight. The phi was more delayed in the children than the adults only for the shortest period, i.e. 0.75 min. The tau for the first order model, either without or with Td, was found to be no difference between children and adults (44.7 vs. 45.9 s (without Td), 34.9 vs. 42.3 s (with Td)). Td, however, was longer in the children (6.6 vs. 2.3 s). The goodness of fit for the first order model with Td was better than that without Td in children, i.e. due to the difference of phi for 0.75 min period, whereas the HR dynamics in adults was appropriately described by first order model without Td. It is concluded that the fundamental control of HR to sinusoidal exercise between children and adults was not appreciably different, except for a small Td difference at high sinusoidal frequency.

Laryngeal reflex apnea is blunted during and after hindlimb muscle contraction in sheep.

This study was carried out on seven chloralose-anesthetized sheep and was designed to investigate the role of muscular afferent fiber stimulation on the duration of reflex apnea triggered by laryngeal stimulation (LS). In six animals, injection of distilled water onto the laryngeal mucosa provoked a 15.7 +/- 1.0 s (mean +/- SE) apnea associated with a rise in systemic blood pressure (+7 +/- 0.8 Torr). Electrically induced contractions (EIC) of the hindlimb muscles doubled the metabolic rate and ventilation and reduced the duration of the apnea produced by LS to 7.4 +/- 1.0 s (P < 0.01). Apnea duration was still reduced during the first minute after the cessation of EIC (7.2 +/- 1.1 s, P < 0.01) but returned to control after a 5-min recovery period (16.7 +/- 1.6 s). The apnea triggered by LS was also reduced during EIC when the venous return was impeded by occluding the inferior vena cava (5.2 +/- 1.1 s, P < 0.01), despite a profound hypocapnia (20.7 +/- 0.3 Torr). The duration of apnea was not significantly affected (14.2 +/- 1.4 s) by breathing a 6% CO2-14% O2 in N2 gas mixture that roughly mimicked the alveolar gas composition when the apnea turned off. These results suggest that chemical drive has a negligible role in the fast reinitiation of breathing after LS during muscular stimulation. Stimulation of muscle afferent fibers does, however, appear to be a potent source of ventilatory reflexes capable of counteracting the inhibition of breathing resulting from laryngeal stimulation. Conversely, it is postulated that any reduction in somatic afferent traffic during this type of reflex apnea, including that resulting from the LS-induced systemic vasoconstriction, may delay the termination of apnea.

Vascular distension in muscles contributes to respiratory control in sheep.

It has recently been proposed that afferent fibers from skeletal muscle could sense the state of the microvascular circulation, linking ventilation to the degree of peripheral perfusion or vascular distension (Huszczuk et al., Respir. Physiol., 91:207-226, 1993). Ventilatory and circulatory responses to manipulation of peripheral vascular pressures in the hind limbs of anaesthetized (sodium thiopental) sheep were examined. Inflatable balloons were placed at the caudal ends of the abdominal aorta and the vena cava (Vc). Aortic (Ao) occlusion induced a consistent normocapnic decrease in minute ventilation (VE). In contrast, VE increased significantly during vena cava obstruction, leading to hypocapnia. Small changes in systemic blood pressure were observed (+7 mmHg for Ao occlusion and -12 mmHg during Vc obstruction). Moreover, inflation of the caval balloon superimposed on a previously established Ao occlusion, preventing venous drainage of anastomotic inflow, resulted in a significant rise in distal vascular pressures with trivial changes in systolic blood pressure. This led to a gradual rise of VE, despite further reduction of the CO2 flux to the lungs. The subsequent deflation of the aortic balloon, exposing the hindlimb vasculature to aortic pressure, resulted in an even more profound hypocapnic hyperpnea. The concurrent arterial blood pressure changes were too small to possibly involve the ventilatory component of the arterial baroreflex. We therefore hypothesize, that perfusion-related afferent signals within the muscles could contribute to respiratory homeostasis by maintaining ventilation of the lungs commensurate with the circulatory state of the muscular apparatus.

Femoral vascular occlusion and ventilation during recovery from heavy exercise.

Ventilation and cardiac output subside gradually following cessation of exercise, which is commonly linked to the slow wash-out of materials from the recovering muscles. The effect of hindering the removal of the metabolic products of heavy cycle exercise on the kinetics of ventilation and gas exchange was studied in 5 subjects by occluding the femoral circulation with cuffs during the first 2 min of recovery (15 tests). Fifteen undisturbed recoveries served as controls. Compared to spontaneous recovery, circulatory obstruction induced an immediate (from the first breath) decrease in minute ventilation (VE), while end-tidal CO2 (PETCO2) as well as lactate and K+ in venous blood at forearm did not change significantly. A ventilatory deficit of 27 +/- 9 L was observed from the 2 min of occlusion. Following cuff deflation, VE rose 2-3 breaths after PETCO2 began to increase in every subject. The mechanisms of the normocapnic reduction of VE during occlusion, as well as the rise of ventilation following cuff release, are still unclear. However, these results argue against any significant role for hyperpnea-inducing intramuscular chemoreception, or point to muscular perfusion as a prerequisite of such a mechanism to operate.

Ventilatory dynamics in children and adults during sinusoidal exercise.

The ventilatory response to sinusoidally varying exercise was studied in five adults and seven prepubertal children to determine whether the faster kinetics of ventilation observed in children during abrupt changes in exercise intensity remained more rapid when exercise intensity varied continuously. Each subject exercised on a cycle ergometer first against a constant load and then against a load fluctuating over six different periods ranging from 0.75 to 10 min. The pedal rate was kept constant for all loads. The inspiratory minute ventilation was determined breath-by-breath. Amplitude (A) and phase angle (phi) of the fundamental component and the first harmonics of the ventilatory response were calculated by Fourier analysis for an integer number of waves for each period. From the relationship between A, phi and frequency, dynamic parameters of a first order model with and without delay were compared between adults and children. Firstly we found that the ventilatory time constant was significantly faster in children: 49.7 (SD 9.1) s vs 74.6 (SD 11.1) s (P less than 0.01). Secondly, the change in A and phi with the frequency was not however characteristic of a first order system without delay in most of the subjects (phi greater than 90 degrees for the shorter periods). Thirdly, even when the ventilatory control system was described as a first order model with a positive delay, time constants remained significantly shorter in children: 45.6 (SD 5.7) s vs 67.4 (SD 13) s (P less than 0.01). The ability to increase ventilation faster in children appeared to be a characteristic of the ventilatory control system during exercise independent of the type of drive used.