Thyroarytenoid muscle activity during hypoxia in awake lambs

It is generally accepted that hypoxia in early life results in active laryngeal braking of expiratory airflow via the recruitment of glottic adductor muscles. We examined the electromyogram expiratory activity of the thyroarytenoid muscle in seven 11- to 18-day-old awake nonsedated lambs exposed to an inspired O2 fraction of 0.08 for 18 min. The lambs breathed through a face mask and a pneumotachograph. During baseline prehypoxic breathing, the thyroarytenoid muscle was largely inactive in each awake lamb. Unexpectedly, no recruitment of the thyroarytenoid muscle was recorded during hypoxia in any of the seven lambs; simultaneous examination of the flow-volume curves revealed an absence of expiratory airflow braking. Also unexpectedly, marked expiratory activity of the thyroarytenoid muscle was recorded, with each expiration occurring within less than 10 s after the return to room air. The resulting delay of expiration was apparent in the flow-volume loops. Thus, in awake 11- to 18-day-old lambs, 1) active expiratory glottic adduction is absent during hypoxia and 2) a return from hypoxia to room air results in prolonged expiration as well as active glottic adduction that controls end-expiratory lung volume.     

Sensation of dyspnea during hypercapnia, exercise, and voluntary hyperventilation

To determine whether the intensity of dyspnea at a given level of respiratory motor output depends on the nature of the stimulus to ventilation, we compared the sensation of difficulty in breathing during progressive hypercapnia (HC) induced by rebreathing, during incremental exercise (E) on a cycle ergometer, and during isocapnic voluntary hyperventilation (IVH) in 16 normal subjects. The sensation of difficulty in breathing was rated at 30-s intervals by use of a visual analog scale. There were no differences in the level of ventilation or the base-line intensity of dyspnea before any of the interventions. The intensity of dyspnea grew linearly with increases in ventilation during HC [r = 0.98 +/- 0.02 (SD)], E (0.95 +/- 0.03), and IVH (0.95 +/- 0.06). The change in intensity of dyspnea produced by a given change in ventilation was significantly greater during HC [0.27 +/- 0.04 (SE)] than during E (0.12 +/- 0.02, P less than 0.01) and during HC (0.30 +/- 0.04) than during IVH (0.16 +/- 0.03, P less than 0.01). The difference in intensity of dyspnea between HC and E or HC and IVH increased as the difference in end-tidal PCO2 widened, even though the time course of the increase in ventilation was similar. No significant differences were measured in the intensity of dyspnea that occurred with changes in ventilation between E and IVH. These results indicate that under nearisocapnic conditions the sensation of dyspnea produced by a given level of ventilation seems not to depend on the method used to produce that level of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyroarytenoid muscle activity during loaded and nonloaded breathing in adult humans

Previous fiber-optic studies in humans have demonstrated narrowing of the glottic aperture in expiration during application of expiratory resistive loads. Nine healthy subjects were studied to determine the effect of expiratory resistive loads on the electromyographic activity of the thyroarytenoid (TA) muscle, a vocal cord adductor. Four of the nine subjects also underwent the application of inspiratory resistive loads and voluntary prolongation of either inspiratory (TI) or expiratory (TE) time. TA activity was recorded by intramuscular hooked-wire electrodes. During quiet breathing in all subjects, the TA was phasically active on expiration and often tonically active throughout the respiratory cycle. TA expiratory activity progressively increased with increasing levels of expiratory load. Inspiratory loads resulted in increased TA "inspiratory" activity. Voluntary prolongation of TE to times similar to those reached during loaded breathing induced increases in TA expiratory activity similar to those reached during the loaded state. Voluntary prolongation of TI was associated with an increase in TA inspiratory activity. Similar increases in TI during inspiratory loading or voluntary conditions were associated with comparable increases in TA inspiratory activity in three of the four subjects. In conclusion, increased activation of TA during the application of expiratory resistive loads implies that the reported narrowing of glottic aperture during expiratory loading is an active phenomenon. Changes in activation of the TA with resistive loads appear to be related to changes in respiratory pattern.     

Interrelations of hypocapnia, hypoxia, cerebral blood flow and electrical activity of the brain under voluntary hyperventilation in humans

Changes of different physiological parameters in human caused by hyperventilation of 3-min and longer duration were investigated and correlated. It was found that during 3-min hyperventilation, resulting in 4.5-5 fold increase of the respiration velocity, similar phasing changes of the central and cerebral haemodynamics occurred. The blood flow velocity according to the rheographic data during the hyperventilation first increases, reaching maximum at 1st - 2nd min of the test, and then decreases, reaching minimum at 2nd - 3rd min after it's end, and then slowly increases. Cerebral blood flow velocity during all the 3 min of the hyperventilation in most of the subjects keeps being increased, and after the test - decreased. At the same time transcutaneous pressure of carbon dioxide changes differently - decreases to minimum (approximately 25 mmHg) at the end of the test and then increases, reaching approximately 90% of the background level, at 5th min after the end of the test. Oxygen saturation of the blood during the test is found to be 98-100% and decreases to 90% at 5th min after it's end, which in overall with cerebral blood flow decrease appears to be the factor of the brain's hypoxia. In different subjects "mirror" changes of the EEG spectral power of different EEG ranges in relation to transcutaneous pressure of carbon dioxide dynamics were revealed by the hyperventilation. Taking into account the factors of duration or recurrence of the hyperventilation is important for the understanding the interrelations of cerebral haemodynamics, hypocapnia, hypoxia and electrical activity of the brain. It was found that after the recurrent hyperventilation of increasing amount (several times in hour by 3 min) cerebral blood flow might decrease markedly against the background of relatively small changes of electrical activity of the brain. The discussing of the data presented in the paper is carried out from the point of view of important role of tissue oxygen utilization mechanisms of the brain in adaptation to hypoxia and hypocapnia.     

Effect of hypercapnia and hypoxia on respiratory muscle activation in humans

We studied the electromyographic activity of the diaphragm (EMGdi) and abdominal external oblique (EMGeo) muscles in response to progressive hypercapnia (HCVR) and hypoxia (HVR) in five normal males. The slopes of the regression lines relating log EMGdi activity to minute volume of ventilation (VE) were steeper during HVR runs than HCVR runs (mean +/- SE, 0.03201 +/- 0.00724 vs. 0.02729 +/- 0.00676, P less than 0.03). Phasic expiratory EMGeo activity was seen in 15 of 15 HCVR runs but in only 6 of 15 HVR runs. Furthermore, the maximum level of VE attained before the onset of EMGeo activity was significantly lower during HCVR runs than during HVR runs (23.1 +/- 2.5 vs. 34.8 +/- 4.01/min, P less than 0.003). We conclude that in awake humans 1) the diaphragm is activated to a greater extent by hypoxia than hypercapnia at a given VE and 2) hypercapnia causes a more consistent recruitment of abdominal expiratory activity at lower VE than does hypoxia.     

Posterior cricoarytenoid activity in normal adults during involuntary and voluntary hyperventilation

The effect of isocapnic hypoxia and hyperoxic hypercapnia on the electrical activity of the posterior cricoarytenoid (PCA) muscle was determined in eight normal adult humans by use of standard rebreathing techniques and was compared with PCA activity during voluntary hyperventilation performed under isocapnic and hypocapnic conditions. PCA activity was recorded with intramuscular hooked-wire electrodes implanted through a fiberoptic nasopharyngoscope. During quiet breathing in all subjects, the PCA was phasically active on inspiration and tonically active throughout the respiratory cycle. At comparable increments in respiratory output, hypercapnia, hypoxia, and voluntary hyperventilation appeared to be associated with similar increases in phasic or tonic PCA activity. During quiet breathing, the onset of phasic PCA activity usually occurred before inspiratory airflow and extended beyond the start of expiratory airflow. The duration of phasic PCA preactivation and postinspiratory phasic PCA activity remained unchanged during progressive hypercapnia and progressive hypoxia. The results, in combination with recent findings for vocal cord adductors, suggest that vocal cord position throughout the respiratory cycle during hyperpnea is actively controlled by simultaneously acting and antagonistic intrinsic laryngeal muscles.     

Contrasting effects of hypoxia and hypercapnia on ventilation and sympathetic activity in humans

We compared the effects of isocapnic hypoxia (IHO) and hyperoxic hypercapnia (HC) on sympathetic nerve activity (SNA) recorded from a peroneal nerve in 13 normal subjects. HC caused greater increases in blood pressure (BP), minute ventilation (VE), and SNA [53 +/- 14% (SE) during HC vs. 21 +/- 7% during IHO; P less than 0.05]. Even at equivalent levels of VE, HC still elicited greater SNA than IHO. However, apnea during HC caused a lesser (P less than 0.05) increase in SNA (91 +/- 26% compared with apnea on room air) than apnea during IHO (173 +/- 50%). Hypercapnic hypoxia resulted in a greater absolute increase in VE (23.6 +/- 2.8 l/min) than the additive increases due to HC alone plus IHO alone (18.0 +/- 1.8 l/min, P less than 0.05). SNA also increased synergistically by 108 +/- 23% with the combined stimulus compared with the additive effect of HC alone plus IHO alone (68 +/- 19%; P less than 0.05). We conclude that 1) HC causes greater increases in VE and SNA than does hypoxia; 2) for the same increase in VE, hypercapnia still causes a greater increase in SNA than hypoxia; however, during apnea, hypoxia causes a much greater increase in SNA than hypercapnia; 3) the inhibitory influence of ventilation on SNA is greater during hypoxia (i.e., predominantly peripheral chemoreceptor stimulation) than hypercapnia (i.e., predominantly central chemoreceptor stimulation); and 4) combined hypoxia and hypercapnia have a synergistic effect on SNA as well as on VE.     

Non-uniform mechanical activity of quadriceps muscle during fatigue by repeated maximal voluntary contraction in humans

To determine the non-uniform surface mechanical activity of human quadriceps muscle during fatiguing activity, surface mechanomyogram (MMG), or muscle sound, and surface electromyogram (EMG) were recorded from the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) muscles of seven subjects during unilateral isometric knee extension exercise. Time- and frequency-domain analyses of MMG and of EMG fatigued by 50 repeated maximal voluntary contractions (MVC) for 3 s, with 3-s relaxation in between, were compared among the muscles. The mean MVC force fell to 49.5 (SEM 2.0)% at the end of the repeated MVC. Integrated EMG decreased in a similar manner in each muscle head, but a marked non-uniformity was found for the decline in integrated MMG (iMMG). The fall in iMMG was most prominent for RF, followed by VM and VL. Moreover, the median frequency of MMG and the relative decrease in that of EMG in RF were significantly greater (P < 0.05) than those recorded for VL and VM. These results would suggest a divergence of mechanical activity within the quadriceps muscle during fatiguing activity by repeated MVC. Accepted: 19 January 1999     

Responses in muscle sympathetic activity to acute hypoxia in humans

Responses in muscle sympathetic activity (MSA) to acute hypoxia were studied in 13 healthy male subjects under hypobaric hypoxic conditions at a simulated altitude of 4,000, 5,000, and 6,000 m. Efferent postganglionic MSA was recorded directly with a tungsten microelectrode inserted percutaneously into the tibial nerve. Heart rate (HR) and respiratory rate (RR) were counted respectively from the R wave of an electrocardiogram and from the respiratory tracing recorded by the strain-gauge method. The average values of the MSA burst rate and total activity of MSA (burst rate x mean burst amplitude) at 4,000, 5,000, and 6,000 m were 36.4 +/- 2.6, 39.1 +/- 3.1, and 40.2 +/- 4.2 (SE) bursts/min and 616 +/- 138, 794 +/- 190, and 764 +/- 227 arbitrary units, respectively. These values were significantly higher than the values of 27.1 +/- 2.9 bursts/min and 446 +/- 28 at sea level. HR increased significantly at altitudes, but RR did not show significant change. Under severe hypoxic conditions beyond 5,000 m, there were large interindividual differences in the MSA responsiveness to hypoxia. The results indicate that MSA is activated under hypoxia by stimulating the chemoreceptors. However, the central controlling mechanisms that would be affected by hypoxia may also influence the MSA responsiveness under severe hypoxia.     

Reflex control of vascular capacitance during hypoxia, hypercapnia, or hypoxic hypercapnia

We tested the hypothesis that the changes in venous tone induced by changes in arterial blood oxygen or carbon dioxide require intact cardiovascular reflexes. Mongrel dogs were anesthetized with sodium pentobarbital and paralyzed with veruronium bromide. Cardiac output and central blood volume were measured by indocyanine green dilution. Mean circulatory filling pressure, an index of venous tone at constant blood volume, was estimated from the central venous pressure during transient electrical fibrillation of the heart. With intact reflexes, hypoxia (arterial PaO2 = 38 mmHg), hypercapnia (PaCO2 = 72 mmHg), or hypoxic hypercapnia (PaO2 = 41; PaCO2 = 69 mmHg) (1 mmHg = 133.32 Pa) significantly increased the mean circulatory filling pressure and cardiac output. Hypoxia, but not normoxic hypercapnia, increased the mean systemic arterial pressure and maintained the control level of total peripheral resistance. With reflexes blocked with hexamethonium and atropine, systemic arterial pressure supported with a constant infusion of norepinephrine, and the mean circulatory filling pressure restored toward control with 5 mL/kg blood, each experimental gas mixture caused a decrease in total peripheral resistance and arterial pressure, while the mean circulatory filling pressure and cardiac output were unchanged or increased slightly. We conclude that hypoxia, hypercapnia, and hypoxic hypercapnia have little direct influence on vascular capacitance, but with reflexes intact, there is a significant reflex increase in mean circulatory filling pressure.     

Erythrocyte adenosine triphosphate depletion during voluntary hyperventilation

Chronic hypophosphatemia in humans is associated with a slow depletion of adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) in erythrocytes, combined with shape alteration, impaired deformability, and viability of the cells. Likewise, incubation of erythrocytes in alkaline solution is associated with ATP depletion. Since in hyperventilation both hypophosphatemia and alkalosis are present, we have investigated red cell organic phosphates, shape, deformability, and osmotic fragility before, during, and after 20 min of voluntary hyperventilation. On the average, red cell ATP decreased by 42%, the blood pH increased by 0.2 units, and plasma inorganic phosphorus decreased by 46% compared with the initial values. Red cell 2,3-DPG, shape, deformability, and osmotic fragility remained unchanged. After the end of hyperventilation ATP increased rapidly to control values in parallel with the normalization of the blood pH, whereas inorganic plasma phosphorus remained at the low level observed during hyperventilation. It is concluded that the combined effects of hypophosphatemia and alkalosis in acute hyperventilation lead to an isolated fall of red cell ATP, which occurs as rapid as after total inhibition of red cell glycolysis in vitro.