Desensitization of the cough reflex during limb muscle contraction in anesthetized rabbits.

The 'cough network' exhibits plasticity at the sensor and integration levels leading to modulation of the strength or pattern of the cough reflex. Little is known about the interactions between cough and human activities, especially during exercise. The present study was designed to determine whether exercise, mimicked by electrically induced muscle contractions, can modify the incidence and/or strength of cough following mechanical stimulation of the trachea in anesthetized rabbits. Thirteen anesthetized, tracheotomized rabbits were studied by a total of 311 tracheal stimulations: 196 at rest and 115 during exercise. During muscle contractions, the incidence of the cough reflex (CR) decreased and the expiration reflex (ER) increased (p < 0.0001). The sensitivity of the CR and ER both decreased during exercise compared to the sensitivity of the CR at rest (p < 0.02), while the strength of the expulsive response remained unchanged. These results indicate that adjustments occurring during muscle contractions likely downregulate tracheal defensive reflexes in anesthetized rabbits.

Nasal stimulation by water down-regulates cough in anesthetized rabbits.

The 'cough center' can be tuned by various afferent inputs, suggesting possible interactions at a central level of neural pathways originating from distant anatomical sites. The present study was designed to determine whether brief mechanical stimulation of the trachea can trigger cough during apnea elicited by nasal instillation of water. Twelve anesthetized, tracheotomized rabbits were studied. Mechanical stimulation of the trachea was performed under 3 conditions: baseline control, after instillation of saline into the nose and during apnea following instillation of water. The baseline breathing pattern did not differ between the 3 conditions. In a series of 171 stimulations, expiration reflex occurred in 81% of stimulations during apnea with a significantly (p<0.0001) lower peak expiratory flow than at baseline or during saline instillation. The incidence of responses comprising a cough reflex was also lower during water instillation than at either baseline or with saline (p<0.0001). These results indicate that stimulation of nasal afferents with distilled water likely down-regulates cough.

H2S induced hypometabolism in mice is missing in sedated sheep.

On the basis of studies performed in mice that showed H(2)S inhalation decreasing dramatically the metabolic rate, H(2)S was proposed as a means of protecting vital organs from traumatic or ischemic episodes in humans. Hypoxia has in fact also long been shown to induce hypometabolism. However, this effect is observed solely in small-sized animals with high VO2 kg(-1), and not in large mammals. Thus, extrapolating the hypometabolic effect of H(2)S to large mammals is questionable and could be potentially dangerous. We measured metabolism in conscious mice (24 g) exposed to H(2)S (60 ppm) at an ambient temperature of 23-24 degrees C. H(2)S caused a rapid and large (50%) drop in gas exchange rate, which occurred independently of the change in body temperature. The metabolic response occurred within less than 3 min. In contrast, sheep, sedated with ketamine and weighing 74 kg did not exhibit any decrease in metabolic rate during a similar challenge at an ambient temperature of 22 degrees C. While a part of H(2)S induced hypometabolism in the mice is related to the reduction in activity, we speculate that the difference between sheep and mice may rely on the nature and the characteristics of the relationship between basal metabolic rate and body weight thus on the different mechanisms controlling resting metabolic rate according to body mass. Therefore, the proposed use of H(2)S administration as a way of protecting vital organs should be reconsidered in view of the lack of hypometabolic effect in a large sedated mammal and of H(2)S established toxicity.

Gated SPECT assessment of left ventricular function is sensitive to small patient motions and to low rates of triggering errors: a comparison with equilibrium radionuclide angiography.

BACKGROUND: Patient displacements and errors in R-wave detection are the main causes of inaccurate acquisition for gated single photon emission computed tomography (SPECT) and equilibrium radionuclide angiography (RNA). This study aimed to compare the influences of both factors between gated SPECT and RNA determinations of left ventricular ejection fraction. METHODS AND RESULTS: On gated SPECT and RNA acquisitions, recorded in 20 patients with coronary artery disease, we simulated the consequences of (1) 3-dimensional patient displacements of low (6.7 mm), moderate (13.4 mm), and high amplitude (20.1 mm) and (2) an erroneous triggering on T waves in 10% to 40% of recorded beats. Absolute values of left ventricular ejection fraction changes from baseline were higher with gated SPECT compared with RNA for patient displacements of low amplitude (5.0% +/- 3.8% vs 1.2% +/- 0.9%, P < .001) or moderate amplitude (10.0% +/- 6.2% vs 3.0% +/- 2.3%, P = .001) but not for patient displacements of high amplitude (12% +/- 9% vs 9% +/- 7%, P = not significant) and inaccurate triggering (for 20% T-wave triggering, 8.9% +/- 3.6% vs 7.9% +/- 3.0%; P = not significant). CONCLUSION: Contrary to RNA, gated SPECT is vulnerable to small patient displacements, and thus, specific efforts might be useful for limiting this potential cause of erroneous results. Both techniques may be affected by low rates of triggering errors, suggesting that small acceptance windows on cycle length should be recommended not only for RNA but also for gated SPECT.

The control of ventilation is dissociated from locomotion during walking in sheep.

This study was designed to test the hypothesis that the frequency response of the systems controlling the motor activity of breathing and walking in quadrupeds is compatible with the idea that supra-spinal locomotor centres could proportionally drive locomotion and ventilation. The locomotor and the breath-by-breath ventilatory and gas exchange (CO2 output (VCO2) and O2 uptake (VO2)) responses were studied in five sheep spontaneously walking on a treadmill. The speed of the treadmill was changed in a sinusoidal pattern of various periods (from 10 to 1 minute) and in a step-like manner. The frequency and amplitude of the limb movements, oscillating at the same period as the treadmill speed changes, had a constant gain with no phase lag (determined by Fourier analysis) regardless the periods of oscillations. In marked contrast, when the periods of speed oscillations decreased, the amplitude (peak-to-mean) of minute ventilation (VE) oscillations decreased sharply and significantly (from 6.1 +/- 0.4 l min(-1) to 1.9 +/- 0.2 l min(-1)) and the phase lag between ventilation and treadmill speed oscillations increased (to 105 +/- 25 degrees during the 1 min oscillation periods). VE response followed VCO2 very closely. The drop in VE amplitude ratio was proportional to that in VCO2 (from 149 +/- 48 ml min(-1) to 38 +/- 5 ml min(-1)) with a slightly longer phase lag for ventilation than for VCO2. These results show that beyond the onset period of a locomotor activity, the amplitude and phase lag of the VE response depends on the period of the walking speed oscillations, tracking the gas exchange rate, regardless of the amplitude of the motor act of walking. Locomotion thus appears unlikely to cause a simple parallel and proportional increase in ventilation in walking sheep.

Isolation of the arterial supply to the carotid and central chemoreceptors in the sheep.

The aim of our study was to develop and validate a simple surgical model in the sheep which allows control of the gas composition of the blood supplying the carotid and central chemosensitive area independently of the rest of the body. This approach was made possible due to the specific features of the cranial circulation in the sheep. An extracorporeal circuit, consisting of a pump and a gas exchanger, was placed at the level of the two common carotid arteries to create a pressure gradient between the carotid and the systemic systems and to reverse blood flow in the vertebral vessels via the occipital arteries. When a pressure gradient of about 40 Torr was created between the systemic and carotid circulation, we found that no blood could reach the carotid bodies and the medulla without passing though the extracorporeal circulation. This was established (1) by measuring vertebral blood flow; and (2) by injecting either a coloured suspension or particles labelled with (99m*)Tc into the systemic or the carotid circulation. The slope of the relationship between minute ventilation (V(E)) and systemic arterial P(CO2) (P(a,CO2)) during high CO(2) inhalation in seven hyperoxic vagotomised and anaesthetised sheep was dramatically reduced, but remained above zero, when P(a,CO2) was maintained constant in the cephalic circuit (0.11 +/- 0.15 vs. 0.70 +/- 0.35 l min(-1) Torr(-1) for the control tests). This residual V(E) response to CO(2) inhalation remains to be explained since it could not be accounted for by any of the chemical or circulatory changes occurring in the cephalic circulation. Nevertheless, this preparation provides an easy method of maintaining chemical and circulatory homeostasis at the chemoreceptor level.

Effects of body position on the ventilatory response following an impulse exercise in humans.

The aim of this study was to identify some of the mechanisms that could be involved in blunted ventilatory response (VE) to exercise in the supine (S) position. The contribution of the recruitment of different muscle groups, the activity of the cardiac mechanoreceptors, the level of arterial baroreceptor stimulation, and the hemodynamic effects of gravity on the exercising muscles was analyzed during upright (U) and S exercise. Delayed rise in VE and pulmonary gas exchange following an impulselike change in work rate (supramaximal leg cycling at 240 W for 12 s) was measured in seven healthy subjects and six heart transplant patients both in U and S positions. This approach allows study of the relationship between the rise in VE and O2 uptake (VO2) without the confounding effects of contractions of different muscle groups. These responses were compared with those triggered by an impulselike change in work rate produced by the arms, which were positioned at the same level as the heart in S and U positions to separate effects of gravity on postexercising muscles from those on the rest of the body. Despite superimposable VO2 and CO2 output responses, the delayed VE response after leg exercise was significantly lower in the S posture than in the U position for each control subject and cardiac-transplant patient (-2.58 +/- 0.44 l and -3.52 +/- 1.11 l/min, respectively). In contrast, when impulse exercise was performed with the arms, reduction of ventilatory response in the S posture reached, at best, one-third of the deficit after leg exercise and was always associated with a reduction in VO2 of a similar magnitude. We concluded that reduction in VE response to exercise in the S position is independent of the types (groups) of muscles recruited and is not critically dependent on afferent signals originating from the heart but seems to rely on some of the effects of gravity on postexercising muscles.