Effect of locomotor respiratory coupling on respiratory evaporative heat loss in the sheep.

During galloping, many animals display 1:1 coupling of breaths and strides. Locomotor respiratory coupling (LRC) may limit respiratory evaporative heat loss (REHL) by constraining respiratory frequency (f). Five sheep were exercised twice each, according to a five-step protocol: 5 min at the walk, 5 min at the trot (trot1), 10 min at the gallop, 5 min at the trot (trot2), and 5 min at the walk. Rectal temperature (T(re)), stride frequency, f, REHL, and arterial CO(2) tension and pH were measured at each step. Tidal volume (VT) was calculated. LRC was observed only during galloping. The coupling ratio remained at 1:1 while VT increased continuously during galloping, causing REHL to increase from 2.9 +/- 0.2 (SE) W/kg at the end of trot1 to a peak of 5.3 +/- 0.3 W/kg. T(re) rose from 39.0 +/- 0.1 degrees C preexercise to 40.2 +/- 0.2 degrees C at the end of galloping. At the gallop-trot2 transition, VT fell and f rose, despite a continued rise in T(re). Arterial CO(2) tension fell from 36.5 +/- 1.1 Torr preexercise to 31.8 +/- 1.4 Torr by the end of trot1 and then further to 21.5 +/- 1.2 Torr by the end of galloping, resulting in alkalosis. In conclusion, LRC did not prevent increases in REHL in sheep because VT increased. The increased VT caused hypocapnia and presumably elevated the cost of breathing.     

Differential sensitivities of cerebral and brachial blood flow to hypercapnia in humans.

Although it is known that the vasculatures of the brain and the forearm are sensitive to changes in arterial Pco(2), previous investigations have not made direct comparisons of the sensitivities of cerebral blood flow (CBF) (middle cerebral artery blood velocity associated with maximum frequency of Doppler shift; Vp) and brachial blood flow (BBF) to hypercapnia. We compared the sensitivities of Vp and BBF to hypercapnia in humans. On the basis of the critical importance of the brain for the survival of the organism, we hypothesized that Vp would be more sensitive than BBF to hypercapnia. Nine healthy males (30.1 +/- 5.2 yr, mean +/- SD) participated. Euoxic hypercapnia (end-tidal Po(2) = 88 Torr, end-tidal Pco(2) = 9 Torr above resting) was achieved by using the technique of dynamic end-tidal forcing. Vp was measured by transcranial Doppler ultrasound as an index of CBF, whereas BBF was measured in the brachial artery by echo Doppler. Vp and BBF were measured during two 60-min trials of hypercapnia, each trial separated by 60 min. Since no differences in the responses were found between trials, data from both trials were averaged to make comparisons between Vp and BBF. During hypercapnia, Vp and BBF increased by 34 +/- 8 and 14 +/- 8%, respectively. Vp remained elevated throughout the hypercapnic period, but BBF returned to baseline levels by 60 min. The Vp CO(2) sensitivity was greater than BBF (4 +/- 1 vs. 2 +/- 1%/Torr; P < 0.05). Our findings confirm that Vp has a greater sensitivity than BBF in response to hypercapnia and show an adaptive response of BBF that is not evident in Vp.     

Effects of human pregnancy on the ventilatory chemoreflex response to carbon dioxide

This study examined the effects of human pregnancy on the central chemoreflex control of breathing. Subjects were two groups (n=11) of pregnant subjects (PG, gestational age, 36.5+/-0.4 wk) and nonpregnant control subjects (CG), equated for mean age, body height, prepregnant body mass, parity, and aerobic fitness. All subjects performed a hyperoxic CO2 rebreathing procedure, which includes prior hyperventilation and maintenance of iso-oxia. Resting blood gases and plasma progesterone and estradiol concentrations were measured. During rebreathing trials, end-tidal Pco2 increased, whereas end-tidal Po2 was maintained at a constant hyperoxic level. The point at which ventilation (Ve) began to rise as end-tidal Pco2 increased was identified as the central chemoreflex ventilatory recruitment threshold for CO2 (VRTco2). Ve levels below (basal Ve) and above (central chemoreflex sensitivity) the VRTco2 were determined. The VRTco2 was significantly lower in the PG vs. CG (40.5+/-0.8 vs. 45.8+/-1.6 Torr), and both basal Ve (14.8+/-1.1 vs. 9.3+/-1.6 l/min) and central chemoreflex sensitivity (5.07+/-0.74 vs. 3.16+/-0.29 l.min-1.Torr-1) were significantly higher in the PG vs. CG. Pooled data from the two groups showed significant correlations for resting arterial Pco2 with basal Ve, central chemoreflex sensitivity, and the VRTco2. The VRTco2 was also correlated with progesterone and estradiol concentrations. These data support the hypothesis that pregnancy decreases the threshold and increases the sensitivity of the central chemoreflex response to CO2. These changes may be due to the effects of gestational hormones on chemoreflex and/or nonchemoreflex drives to breathe.     

Gas exchange during exercise in habitually active asthmatic subjects.

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency.     

Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography.

Hypercapnia has been shown in animal experiments to induce pulmonary hypertension. This study measured the sensitivity and time course of the human pulmonary vascular response to sustained (4 h) hypercapnia and hypocapnia. Twelve volunteers undertook three protocols: 1) 4-h euoxic (end-tidal Po(2) = 100 Torr) hypercapnia (end-tidal Pco(2) was 10 Torr above normal), followed by 2 h of recovery with euoxic eucapnia; 2) 4-h euoxic hypocapnia (end-tidal Pco(2) was 10 Torr below normal) followed by 2 h of recovery; and 3) 6-h air breathing (control). Pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by using Doppler echocardiography via the maximum tricuspid pressure gradient during systole. Results show progressive changes in pressure gradient over 1-2 h after the onset or offset of the stimuli, and sensitivities of 0.6 to 1 Torr change in pressure gradient per Torr change in end-tidal Pco(2). The human pulmonary circulatory response to changes in Pco(2) has a slower time course and greater sensitivity than is commonly assumed. Vascular tone in the normal pulmonary circulation is substantial.     

Respiratory adaptations to dead space loading during maximal incremental exercise

We examined the effects of dead space (VD) loading on breathing pattern during maximal incremental exercise in eight normal subjects. Addition of external VD was associated with a significant increase in tidal volume (VT) and decrease in respiratory frequency (f) at moderate and high levels of ventilation (VI); at a VI of 120 l/min, VT and f with added VD were 3.31 +/- 0.33 liters and 36.7 +/- 6.7 breaths/min, respectively, compared with 2.90 +/- 0.29 liters and 41.8 +/- 7.3 breaths/min without added VD. Because breathing pattern does not change with CO2 inhalation during heavy exercise (Gallagher et al. J. Appl. Physiol. 63: 238-244, 1987), the breathing pattern response to added VD is probably a consequence of alteration in the PCO2 time profile, possibly sensed by the carotid body and/or airway-pulmonary chemoreceptors. The increase in VT during heavy exercise with VD loading indicates that the tachypneic breathing pattern of heavy exercise is not due to mechanical limitation of maximum ventilatory capacity at high levels of VT.     

Running and shipping elevate plasma levels of beta-endorphin-like substance (B-END-LI) in thoroughbred horses

A specific RIA for beta-endorphin (B-END) was developed to measure horse plasma levels of B-END-like material (B-END-LI) during exercises and shipping. Three exercise speeds and durations were: trot at 260-300 m/min for 10 min; slow gallop at 390-420 m/min for 5 min and fast gallop at 700-800 m/min for 2 min. Blood samples were taken from 4 horses before, immediately after, 30 and 60 min after exercise. Trotting increased plasma B-END-LI from a basal level of 109 +/- 7 pg/ml to 172 +/- 22 at the end of exercise and returned to 127 +/- 17 and 107 +/- 10 pg/ml at 30 and 60 min after exercise. Similar results were obtained in slow gallop (121 +/- 6 to 210 +/- 17 then 155 +/- 8 and 131 +/- 11 pg/ml). However, fast gallop caused the greatest increase (352%) in B-END-LI to concentrations of 544 +/- 93 pg/ml and 276 +/- 74 pg/ml at 5 and 30 min after exercise. Plasma B-END-LI returned to 199 +/- 46 pg/ml in 1 hr. Sequential exercises of trot, slow and fast gallop were conducted in 6 horses. Plasma B-END-LI were 116 +/- 19 pg/ml (pre-exercise), 198 +/- 21 (trot), 361 +/- 51 (slow gallop), 500 +/- 57 (fast gallop) and 248 +/- 29, 171 +/- 24, 143 +/- 20 and 139 +/- 21 pg/ml at 0.5, 1, 2 and 3 hr, respectively, following exercises. Transportation in horse trailer also significantly increased plasma levels of B-END-LI from a basal level of 138 +/- 12 to 196 +/- 24 pg/ml within 30 min and this levels were maintained at 45 min (177 +/- 3 pg/ml). Plasma levels of B-END-LI began to decline at 60 min of shipping. These results showed that plasma B-END-LI was increased in all speeds of exercise and by shipping and returned to pre-exercise and pre-shipping level in 30 min except fast gallop which returned to pre-exercise level in 1 hr.     

Exposure to hypoxia produces long-lasting sympathetic activation in humans.

The relative contributions of hypoxia and hypercapnia in causing persistent sympathoexcitation after exposure to the combined stimuli were assessed in nine healthy human subjects during wakefulness. Subjects were exposed to 20 min of isocapnic hypoxia (arterial O(2) saturation, 77-87%) and 20 min of normoxic hypercapnia (end-tidal P(CO)(2), +5.3-8.6 Torr above eupnea) in random order on 2 separate days. The intensities of the chemical stimuli were manipulated in such a way that the two exposures increased sympathetic burst frequency by the same amount (hypoxia: 167 +/- 29% of baseline; hypercapnia: 171 +/- 23% of baseline). Minute ventilation increased to the same extent during the first 5 min of the exposures (hypoxia: +4.4 +/- 1.5 l/min; hypercapnia: +5.8 +/- 1.7 l/min) but declined with continued exposure to hypoxia and increased progressively during exposure to hypercapnia. Sympathetic activity returned to baseline soon after cessation of the hypercapnic stimulus. In contrast, sympathetic activity remained above baseline after withdrawal of the hypoxic stimulus, even though blood gases had normalized and ventilation returned to baseline levels. Consequently, during the recovery period, sympathetic burst frequency was higher in the hypoxia vs. the hypercapnia trial (166 +/- 21 vs. 104 +/- 15% of baseline in the last 5 min of a 20-min recovery period). We conclude that both hypoxia and hypercapnia cause substantial increases in sympathetic outflow to skeletal muscle. Hypercapnia-evoked sympathetic activation is short-lived, whereas hypoxia-induced sympathetic activation outlasts the chemical stimulus.     

Large lesions in the pre-B?tzinger complex area eliminate eupneic respiratory rhythm in awake goats.

In awake goats, 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-B?tzinger complex (pre-B?tzC) area with saporin conjugated to substance P results in transient disruptions of the normal pattern of eupneic respiratory muscle activation (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, and Forster HV. J Appl Physiol 97: 1620-1628, 2004). Therefore, the purpose of these studies was to determine whether large or total lesioning in the pre-B?tzC area of goats would eliminate phasic diaphragm activity and the eupneic breathing pattern. In awake goats that already had 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-B?tzC area, bilateral ibotenic acid (10 microl, 50 mM) injection into the pre-B?tzC area resulted in a tachypneic hyperpnea that reached a maximum (132 +/- 10.1 breaths/min) approximately 30-90 min after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (arterial Po2 approximately 40 Torr) and hypercapnia (arterial Pco2 approximately 60 Torr), and, 11 +/- 3 min after the peak tachypnea, respiratory failure was followed by cardiac arrest in three airway-intact goats. However, after the peak tachypnea in four tracheostomized goats, mechanical ventilation was initiated to maintain arterial blood gases at control levels, during which there was no phasic diaphragm or abdominal muscle activity. When briefly removed from the ventilator (approximately 90 s), these goats became hypoxemic and hypercapnic. During this time, minimal, passive inspiratory flow resulted from phasic abdominal muscle activity. We estimate that 70% of the neurons within the pre-B?tzC area were lesioned in these goats. We conclude that, in the awake state, the pre-B?tzC is critical for generating a diaphragm, eupneic respiratory rhythm, and that, in the absence of the pre-B?tzC, spontaneous breathing reflects the activity of an expiratory rhythm generator.     

Exercise response after rapid intravenous infusion of saline in healthy humans.

Patients with chronic heart failure have an abnormal pattern of exercise ventilation (Ve), characterized by small tidal volumes (Vt), increased alveolar ventilation, and elevated physiological dead space (Vd/Vt). To investigate whether increased lung water in isolation could reproduce this pattern of exercise ventilation, 30 ml/kg of saline were rapidly infused into nine normal subjects, immediately before a symptom-limited incremental exercise test. Saline infusion significantly reduced forced vital capacity, 1-s forced expiratory volume, and alveolar volume (P < 0.01 for all). After saline, exercise ventilation assessed by the Ve/Vco(2) slope increased from 24.9 +/- 2.4 to 28.0 +/- 2.9 l/l, (P < 0.0002), associated with a small decrease in arterial Pco(2), but without changes in Vt, Vd/Vt, or alveolar-arterial O(2) difference. A reduction in maximal O(2) uptake of 175 +/- 184 ml/min (P < 0.02) was observed in the postsaline infusion exercise studies, associated with a consistent reduction in maximal exercise heart rate (8.1 +/- 5.9 beats/min, P < 0.01), but without a change in the O(2) pulse. Therefore, infusion of saline to normal subjects before exercise failed to reproduce either the increase in Vd/Vt or the smaller exercise Vt described in heart failure patients. The observed increase in Ve can be attributed to dilution acidosis from infusion of the bicarbonate-free fluid and/or to afferent signals from lung and exercising muscles. The reduction in maximal power output, maximal O(2) uptake, and heart rate after saline infusion may be linked to accumulation of edema fluid in exercising muscle, impairing the diffusion of O(2) to muscle mitochondria.     

Lesions in the cerebellar fastigial nucleus have a small effect on the hyperpnea needed to meet the gas exchange requirements of submaximal exercise.

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is necessary for the hyperpnea to meet the gas exchange needs of submaximal exercise. Bilateral stainless steel microtubules were implanted in the cerebellum inside (n = 12) or outside (n = 2) the CFN for injection (0.5 to 10 microl) of the neurotoxin ibotenic acid. All goats had difficulty maintaining normal posture and walking for up to 1 mo after the implantation of the microtubules and again for hours or days after the neurotoxin was injected. Postmortem histology indicated there were 55% fewer living neurons (P < 0.001, n = 9, 3,720 +/- 553 vs. 1,670 +/- 192) in the CFN of the experimental goats compared with a control group of goats. As is typical for goats before implantation of the microtubules, the decrease in arterial Pco(2) from rest during mild and moderate treadmill exercise was 2.0 +/- 0.39 and 3.5 +/- 0.45 Torr, respectively. Implantation of the microtubules did not significantly change this exercise hyperventilation. However, neurotoxic lesioning with 10 mul ibotenic acid significantly (P < 0.05) attenuated the decrease in arterial Pco(2) by 1.3 and 2.8 Torr at the first and second workload, respectively. The modest attenuation of the exercise hypocapnia at both workloads in CFN-lesioned goats suggests that the CFN is part of the control system that enables the ventilatory response to meet the gas exchange requirements of submaximal exercise.     

Ventilatory response of spinal cord-lesioned subjects to electrically induced exercise

Seven human spinal cord-lesioned subjects (SPL) underwent electrically induced muscle contractions (EMC) of the quadriceps and hamstring muscles for 10 min: 5 min control, 2 min with venous return from the legs occluded, and 3 min postocclusion. Group mean changes in CO2 output compared with rest were +107 +/- 30.6, +21 +/- 25.7, and +192 +/- 37.0 (SE) ml/min during preocclusion, occlusion, and postocclusion EMC, respectively. Mean arterial CO2 partial pressure (PaCO2) obtained from catheterized radial arteries at 15- to 30-s intervals showed a significant (P less than 0.05) hypocapnia (36.2 Torr) during occlusion and a significant (P less than 0.05) hypercapnia (38.1 Torr) postocclusion relative to a group mean preocclusion EMC PaCO2 of 37.5 Torr. Relative to preocclusion EMC, expired ventilation (VE) decreased during occlusion and increased after release of occlusion. However, changes in VE always occurred after changes in end-tidal PCO2 (mean 41 s after occlusion and 10 s after release of occlusion). In the two subjects investigated during hyperoxia, the VE and PaCO2 responses to occlusion and release did not differ from normoxia. We conclude that the data do not support mediation of the EMC hyperpnea in SPL by humoral mechanisms that others have proposed for mediation of the exercise hyperpnea in spinal cord-intact humans.     

Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA.

Breathing 100% O2 at 1 atmosphere absolute (ATA) is known to be associated with a decrease in cerebral blood flow (CBF). It is also accompanied by a fall in arterial Pco2 leading to uncertainty as to whether the cerebral vasoconstriction is totally or only in part caused by arterial hypocapnia. We tested the hypothesis that the increase in arterial Po2 while O2 was breathed at 1.0 ATA decreases CBF independently of a concurrent fall in arterial Pco2. CBF was measured in seven healthy men aged 21-62 yr by using noninvasive continuous arterial spin-labeled-perfusion MRI. The tracer in this technique, magnetically labeled protons in blood, has a half-life of seconds, allowing repetitive measurements over short time frames without contamination. CBF and arterial blood gases were measured while breathing air, 100% O2, and 4 and 6% CO2 in air and O2 backgrounds. Arterial Po2 increased from 91.7 +/- 6.8 Torr in air to 576.7 +/- 18.9 Torr in O2. Arterial Pco2 fell from 43.3 +/- 1.8 Torr in air to 40.2 +/- 3.3 Torr in O2. CBF-arterial Pco2 response curves for the air and hyperoxic runs were nearly parallel and separated by a distance representing a 28.7-32.6% decrement in CBF. Regression analysis confirmed the independent cerebral vasoconstrictive effect of increased arterial Po2. The present results also demonstrate that the magnitude of this effect at 1.0 ATA is greater than previously measured.     

CO2 does not affect passive exercise ventilatory decline.

Breathing increases abruptly at the start of passive exercise, stimulated by afferent feedback from the moving limbs, and declines toward a steady-state hyperpnea as exercise continues. This decline has been attributed to decreased arterial CO2 levels and adaptation in afferent feedback; however, the relative importance of these two mechanisms is unknown. To address this issue, we compared ventilatory responses to 5 min of passive leg extension exercise performed on 10 awake human subjects (6 men and 4 women) in isocapnic and poikilocapnic conditions. End-tidal Pco2 decreased significantly during poikilocapnic (Delta = -1.5 +/- 0.5 Torr, P < 0.001), but not isocapnic, passive exercise. Despite this difference, the ventilatory responses to passive exercise were not different between the two conditions. Using the fast changes in ventilation at the start (5.46 +/- 0.40 l/min, P < 0.001) and end (3.72 +/- 0.33 l/min, P < 0.001) of passive exercise as measures of the drive to breathe from afferent feedback, we found a decline of 68%. We conclude that the decline in ventilation during passive exercise is due to an adaptation in the afferent feedback from the moving limbs, not a decline in CO2 levels.     

Alveolar epithelial integrity in athletes with exercise-induced hypoxemia.

The effect of incremental exercise to exhaustion on the change in pulmonary clearance rate (k) of aerosolized (99m)Tc-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) and the relationship between k and arterial PO(2) (Pa(O(2))) during heavy work were investigated. Ten male cyclists (age = 25 +/- 2 yr, height = 180.9 +/- 4.0 cm, mass = 80.1 +/- 9.5 kg, maximal O(2) uptake = 5. 25 +/- 0.35 l/min, mean +/- SD) completed a pulmonary clearance test shortly (39 +/- 8 min) after a maximal O(2) uptake test. Resting pulmonary clearance was completed >/=24 h before or after the exercise test. Arterial blood was sampled at rest and at 1-min intervals during exercise. Minimum Pa(O(2)) values and maximum alveolar-arterial PO(2) difference ranged from 73 to 92 Torr and from 30 to 55 Torr, respectively. No significant difference between resting k and postexercise k for the total lung (0.55 +/- 0.20 vs. 0. 57 +/- 0.17 %/min, P > 0.05) was observed. Pearson product-moment correlation indicated no significant linear relationship between change in k for the total lung and minimum Pa(O(2)) (r = -0.26, P > 0.05). These results indicate that, averaged over subjects, pulmonary clearance of (99m)Tc-DTPA after incremental maximal exercise to exhaustion in highly trained male cyclists is unchanged, although the sampling time may have eliminated a transient effect. Lack of a linear relationship between k and minimum Pa(O(2)) during exercise suggests that exercise-induced hypoxemia occurs despite maintenance of alveolar epithelial integrity.     

Cerebral and myocardial blood flow responses to hypercapnia and hypoxia in humans

In humans, cerebrovascular responses to alterations in arterial Pco(2) and Po(2) are well documented. However, few studies have investigated human coronary vascular responses to alterations in blood gases. This study investigated the extent to which the cerebral and coronary vasculatures differ in their responses to euoxic hypercapnia and isocapnic hypoxia in healthy volunteers. Participants (n = 15) were tested at rest on two occasions. On the first visit, middle cerebral artery blood velocity (V(P)) was assessed using transcranial Doppler ultrasound. On the second visit, coronary sinus blood flow (CSBF) was measured using cardiac MRI. For comparison with V(P), CSBF was normalized to the rate pressure product [an index of myocardial oxygen consumption; normalized (n)CSBF]. Both testing sessions began with 5 min of euoxic [end-tidal Po(2) (Pet(O(2))) = 88 Torr] isocapnia [end-tidal Pco(2) (Pet(CO(2))) = +1 Torr above resting values]. Pet(O(2)) was next held at 88 Torr, and Pet(CO(2)) was increased to 40 and 45 Torr in 5-min increments. Participants were then returned to euoxic isocapnia for 5 min, after which Pet(O(2)) was decreased from 88 to 60, 52 and 45 Torr in 5-min decrements. Changes in V(P) and nCSBF were normalized to isocapnic euoxic conditions and indexed against Pet(CO(2)) and arterial oxyhemoglobin saturation. The V(P) gain for euoxic hypercapnia (%/Torr) was significantly higher than nCSBF (P = 0.030). Conversely, the V(P) gain for isocapnic hypoxia (%/%desaturation) was not different from nCSBF (P = 0.518). These findings demonstrate, compared with coronary circulation, that the cerebral circulation is more sensitive to hypercapnia but similarly sensitive to hypoxia.     

Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep.

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired P(O2). We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78-80%), and hyperoxia (inspired O2 fraction = 50-52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sigh-like breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 +/- 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 +/- 0.8 s; P < 0.05), whereas hyperoxia prolonged it (71.5 +/- 13.8 s; P < 0.01). The apneic threshold end-tidal P(CO2) (Pet(CO2)) was defined as the Pet(CO2)) at the onset of apnea. During hypoxia, the apneic threshold Pet(CO2) was higher (38.9 +/- 1.7 Torr; P < 0.01) compared with normoxia (35.8 +/- 1.1; Torr); during hyperoxia, it was lower (33.0 +/- 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic Pet(CO2) and apneic threshold Pet(CO2) was smaller during hypoxia (3.0 +/- 1.0 Torr P < 001) and greater during hyperoxia (10.6 +/- 0.8 Torr; P < 0.05) compared with normoxia (8.0 +/- 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic Pet(CO2) was increased by hypoxia (3.44 +/- 0.63 l.min(-1).Torr(-1); P < 0.05) and decreased by hyperoxia (0.63 +/- 0.04 l.min(-1).Torr(-1); P < 0.05) compared with normoxia (0.79 +/- 0.05 l.min(-1).Torr(-1)). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.     

Effect of acute hypercapnia on limb muscle contractility in humans

The effect of acute hypercapnia on skeletal muscle contractility and relaxation rate was investigated. The contractile force of fresh and fatigued quadriceps femoris (QF) and adductor pollicis (AP) was studied in normal humans by use of electrical stimulation. Maximum relaxation rate from stimulated contractions was measured for both muscles. Acute hypercapnia led to a rapid substantial reduction of contraction force. The respiratory acidosis after 9% CO2 was breathed for 20 min [mean venous blood pH 7.26 and end-tidal PCO2 (PETCO2) 65.1 Torr] reduced 20- and 100-Hz stimulated contractions of QF to 72.8 +/- 4.4 and 80.0 +/- 5.1% of control values, respectively. After 8 and 9% CO2 were breathed for 12 min, AP forces at 20- and 50-Hz stimulation were also reduced. Twitch tension of AP was reduced by a mean of 25.5% when subjects breathed 9% CO2 for 12 min [mean arterialized venous blood pH (pHav) 7.25 and PETCO2 66 Torr]. Over the range of 5% (pHav 7.38 and PETCO2 47 Torr) to 9% CO2, there was a linear relationship between twitch tension loss and pHav, arterialized venous blood PCO2, and PETCO2. Acute respiratory acidosis (mean PETCO2 61 Torr) increased the severity of low-frequency fatigue after intermittent voluntary contractions of AP. At 20 min of recovery, twitch tension was 63.2 +/- 13.4 and 46.8 +/- 16.4% of control value after exercise breathing air and 8% CO2, respectively. Acute hypercapnia (mean PETCO2 65.1 and 60.5 Torr) did not alter the maximum relaxation rate from tetanic contractions of fresh QF and from twitch tensions of AP.     

Response to CO2 in novice closed-circuit apparatus divers and after 1 year of active oxygen diving at shallow depths.

Elevated arterial Pco(2) (hypercapnia) has a major effect on central nervous system oxygen toxicity in diving with a closed-circuit breathing apparatus. The purpose of the present study was to follow up the ability of divers to detect CO(2) and to determine the CO(2) retention trait after 1 year of active oxygen diving with closed-circuit apparatus. Ventilatory and perceptual responses to variations in inspired CO(2) (range: 0-5.6 kPa, 0-42 Torr) during moderate exercise were assessed in Israeli Navy combat divers on active duty. Tests were carried out on 40 divers during the novice oxygen diving phase (ND) and the experienced oxygen diving phase. No significant changes were found between the two phases for the minimal mean inspired Pco(2) that could be detected. The mean (with SD in parentheses) end-tidal Pco(2) during exposure to an inspired Pco(2) of 5.6 kPa (42 Torr) was significantly higher in the novice diving phase than in the experienced diving phase [8.1 kPa (SD 0.7), 62 Torr (SD 5) and 7.8 kPa (SD 0.6), 59 Torr (SD 4), respectively; P < or = 0.001]. One year of shallow oxygen diving activity with a closed-circuit apparatus does not affect the ability to detect CO(2) nor does it lead to increased CO(2) retention; rather, it may even bring about a decrease in this trait. This finding suggests that acquiring experience in oxygen diving with a closed-circuit apparatus at shallow depths does not place the diver at a greater risk of central nervous system oxygen toxicity due to CO(2) retention.     

Metabolic response to maximal exercise of 800 and 2,000 m in the thoroughbred horse

To define the metabolic response to maximal exercise in the thoroughbred horse under field conditions, muscle biopsies and venous blood samples were taken from five horses after a single 800-m gallop and from four horses after a single 2,000-m gallop. Muscle and blood samples were also collected during 60 min of recovery. After exercise muscle ATP contents were decreased by 30 +/- 7 (SD) and 47 +/- 3% after the 800- and 2,000-m gallops, respectively. As indicators of purine catabolism, ammonia and uric acid increased in plasma, the accumulation being greater after the 2,000-m gallop. Blood ammonia peaked immediately after exercise and uric acid after 40-60 min of recovery. Muscle glycogen utilization over the 800- and 2,000-m gallops averaged 2.68 +/- 0.90 and 1.06 +/- 0.12 mmol glucosyl units.kg dry muscle-1.s-1, respectively, and the total used amounted to 27.3 +/- 6.6 and 32.5 +/- 8.8% of the initial store. Muscle lactate accumulation averaged 123.5 +/- 49.7 and 167.3 +/- 20.7 mmol/kg dry muscle, respectively, and declined during recovery with half times of 22.9 +/- 4.2 and 18.9 +/- 6.6 min. Blood lactate peaked 5-10 min after exercise. Exercise resulted in only a small increase in muscle glycerol content, but this continued to rise during recovery reaching 9-12 mmol/kg dry muscle after 20 min. During this time the increase in muscle glycerol content exactly matched the decline in glycerol 3-phosphate.