Relative Hypoventilation Research Articles

Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration.

Purpose:We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors.Methods:We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema.Results:We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema.Conclusion:In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.Summary Statement Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. Key ResultsIn non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

Excessive Erythrocytosis and Chronic Mountain Sickness in the Highest City in the World: A Longitudinal Study

Excessive Erythrocytosis and Chronic Mountain Sickness in the Highest City in the World: A Longitudinal Study

Might a high hemoglobin mass be involved in non-cardiogenic pulmonary edema? The case of the chronic maladaptation to high-altitude in the Andes

Exposure to hypoxic environments when ascending at high altitudes may cause life-threatening pulmonary edema (HAPE) due to a rapid accumulation of extracellular fluid flooding in the pulmonary alveoli. In Andeans, high-altitude adaptation occurs at the expense of being more prone to chronic mountain sickness: relative hypoventilation, excess pulmonary hypertension, and secondary polycythemia. Because HAPE prevalence is high in the Andes, we posit the hypothesis that a high hemoglobine mass may increase HAPE risk. In support of it, high intrapulmonary hypertension along with hyperviscosity produced by polycytemia may enhance sear forces and intravascular hemolysis, thus leading to increased acellular hemoglobin and the subsequent damage of the alveolar and endothelial barrier. It is proposed to investigate the relationship between the vaso-endothelial homeostasis and erythropoiesis in the maladaptation to high altitude and HAPE. This research is especially important when reentry HAPE, since rheologic properties of blood changes with rapid ascent to high altitudes.

ЗМІНА РЕАКТИВНОСТІ СИСТЕМИ ДИХАННЯ ПІД ВПЛИВОМ СТОМЛЕННЯ В ПРОЦЕСІ ТРИВАЛОГО НАПРУЖЕНОГО ФІЗИЧНОГО НАВАНТАЖЕННЯ

Introduction. A change in the complexity of respiratory reactivity in the process of intense athletic training is a reflection of the integration of external and internal factors, one of the important mechanisms for optimizing the respiratory response. Purpose. In order deepen understanding of the role of regulatory factors in increasing the limits of efficiency, it became necessary analyze changes in the reactivity of the respiratory system in the process of tense muscle load, performed up failure. Methods. When performing a long (about 1 hour) load to failure with a relative intensity of 65% of VO 2 max, the dynamics of V E , Q and gas exchange, as well as changes in the level and speed of the respiratory response short-term effects during the performance of long physical work were investigated: 1) step increase the work capacity by 17% from the 40th minute of work, by 33% from the 50th minute of work; 2) temporary (within 30 s) rectangular increase of work capacity by 33% after every 5 minutes of physical work; 3) periodically repeated short-term hypoxic and hypercapnic stimuli using the reverse breathing method. Results. Despite the individual peculiarities of changing the sensitivity of the ventilatory reaction CO 2 during prolonged loading, the obtained data indicate a relative decrease in the acidophilic respiration stimulus at the end of the load on the background of fatigue. There is reason believe that the modification of the reactivity of the respiratory system the load, including the CO 2 -H + -stimulus, largely determined the changes associated with the development of fatigue. During a long load of submaximal intensity of continuous or repeated type of fan reaction and its stimuli in a certain way turned. At the end of such a load on the background of fatigue development there was a relative decrease in ventilation of the lungs and such changes in the gas composition of blood, its acid-base state, which are characteristic of relative hypoventilation of the lungs Conclusion . When performing intense physical activity, the main changes in the development of fatigue are the decrease in the peak values of the reaction, as well as the speed of their deployment. It is possible think that in this regard the nature of the training effects in the initial part of the training session and at the end of it differed. In this case, the highest effect of specially directed means of training of this kind persisted as long as maintaining high levels (peaks) and the rate of deployment of the fan reaction, as well as reactions on VO 2 and VСО 2 . All this points the need take into account the nature of such changes in the reactivity of the respiratory system during the training session and the use of special means for its correction.

Effects on respiration of nonintubated anesthesia in thoracoscopic surgery under spontaneous ventilation.

Thoracoscopic surgery without tracheal intubation [nonintubated video-assisted thoracoscopic surgery (VATS)] is an emerging treatment modality for a wide variety of thoracic procedures. By surgically induced open pneumothorax, the operated lung collapse progressively while the dependent lung is responsible for sufficiency of respiratory function, including oxygenation and ventilation. Encouraging results showed that ventilatory changes and oxygenation could be adequately maintained in major lung resection surgery and in patients with impaired respiratory function. In spite of a relative hypoventilation, mild hypercapnia is inevitable but clinically well tolerated. An understanding the respiratory physiology during surgical pneumothorax, either in awake or sedative status, and an established protocol for conversion into tracheal intubation are essential for patient safety during nonintubated VATS.

Alveolar to Arterial Gas Exchange During Constant-load Exercise in Healthy Active Men and Women

Exercise-induced arterial hypoxemia (EIAH) can result from inadequate hyperventilation and/or inefficient alveolar to arterial gas exchange. For these circumstances to occur demand typically exceeds capacity; as such, EIAH is more often reported in highly trained individuals (∼50%) during progressive maximal exercise. However, it has also been observed during lower levels of exercise in some individuals and is suggested to have a higher incidence in trained women. PURPOSE: To determine if the alveolar to arterial O2 difference (AaDO2) and ventilatory response during constant-load exercise in healthy active, but not highly trained, individuals suggests an innate sex difference that would make females more susceptible to EIAH. METHODS: Thirty-one healthy, active male (M) and 33 female (F) subjects (VO2MAX: 39±7 vs. 31±6mL/min/Kg, M vs. F) completed 18min of exercise on a cycle ergometer (40 and 75% peak W 9min/stage) with the final stage progressing towards maximal by end exercise (VO2: 90±7 vs. 92±9%VO2MAX, M vs. F). At rest and every 3min during exercise arterial blood gases were drawn and cardiac output (Q) was measured, while gas exchange was continuously assessed. Partial pressure of alveolar O2 (PAO2), AaDO2 and change from baseline for PaO2, PaCO2 and SaO2 were calculated. RESULTS: Both males and females demonstrated AaDO2 widening with each 3min increment of exercise (M: 8.6±4.4, 9.2±5.2, 10.3±5.6, 14.9±5.6, 16.5±6.6, 16.3±6.2 vs. F: 7.5±3.7, 8.3±5.0, 9.5±4.1, 14.4±6.9, 16.4±7.1, 19.1±6.0; for minutes 3, 6, 9 at 40% and 12, 15, 18 at 75%). There was no evidence of a difference in ventilatory response or a relative hypoventilation between sexes. No significant arterial hypoxemia was noted, but 6 M (19%) and 5 F (15%) had a drop in SaO2 ≥2% by the final minute of exercise. There was a negative relationship between ΔSaO2 and Q, AaDO2, and ΔPaCO2 during 75%VO2MAX exercise (Q: r= -0.31 p=0.01; AaDO2: r= -0.28 p=0.03; ΔPaCO2: r= -0.43 p=0.00). CONCLUSIONS: There was no evidence of pulmonary gas exchange inefficiencies during exercise that would increase EIAH susceptibility in females. The reported higher incidence of EIAH in highly trained females compared males, therefore appears to be a result of training induced changes rather than innate sex specific inefficiencies. Funding support: NIH HL71478 and AHA 56051Z

Rebuttal to Pro Statements

High-altitude (HA) natives show distinctive physical and functional characteristics that give them an advantage over lowlanders at HA. These advantages are not confined to the cardio-respiratory or hematological systems, as they include indeed the whole organism, and must be reflected in different regions of the brain. In this regard, the reduced cerebrovascular reactivity in HA natives reported by Yan et al., (2011a) was particularly manifested among brain regions involved in cerebral modulation of respiration. Hochachka and co-workers have shown that lower regionby-region brain glucose metabolic rates in HA Quechuas compared to lowlanders may be the result of a defense adaptation against chronic hypoxia (Hochachka et al., 1994). Also, the psychomotor slowing observed in European, Native American, and African altitude groups is proposed to be an adaptive rather than a deficient trait (Hogan et al., 2010). In addition, the very scarce studies in spatial working memory matched by age, gender ratio, educational level, and ancestral lines, show equal accuracy response in HA compared to SL groups, but with more variability in reaction time; and the same activation patterns in their neural pathways (Yan et al., 2011b). Evaluation of the effects of altitude on mood, behavior profile, and cognitive function is complicated by differences between studies, including the specific methods of measurement and type of participants, which explain why there are so few. Since most of the systematic research in these areas has been conducted in exposure to experimental acute or moderate-lasting hypoxia, the results should not be generalized to altitude settings. On the physical side, besides being able to run a complete marathon at 4300 m, superior pulmonary gas-exchange and acidbase state in HA natives was evidenced by Wagner et al. (2002) and Lundby et al. (2004), who compared lowlanders acclimatized to 5260 m with HA natives at the same altitude in Bolivia. During exercise, HA natives showed smaller alveolar-arterial Po2 difference, 40% higher O2-diffusing capacity, and greater lactic acid buffering. In addition, despite lower anaerobic capacities, HA natives were capable of calf muscle work rates equal to those of highly-trained power athletes (Matheson et al., 1991). Also, aerobic exercise capacity of chronic mountain sickness patients with significant erythrocytosis is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of blood and pulmonary O2-diffusion (Groepenhoff et al., 2012). Even though in his later publication (Barcroft, 1925), concluded that acclimatization to HA does not exist, generalizing this concept even to HA natives, Barcroft was very impressed by the physical capacities of the Peruvian Andean natives, and this was certainly an accurate feeling.

Exercise Pathophysiology in Patients With Chronic Mountain Sickness

Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis,severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity. Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test. The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold,of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arterial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001). The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

High-Altitude Disorders: Pulmonary Hypertension: Pulmonary Vascular Disease: The Global Perspective

Globally, it is estimated that > 140 million people live at a high altitude (HA), defined as > 2,500 m (8,200 ft), and that countless others sojourn to the mountains for work, travel, and sport. The distribution of exposure to HA is worldwide, including 35 million in the Andes and > 80 million in Asia, including China and central Asia. HA stress primarily is due to the hypoxia of low atmospheric pressure, but dry air, intense solar radiation, extreme cold, and exercise contribute to acute and chronic disorders. The acute disorders are acute mountain sickness (also known as soroche), HA cerebral edema, and HA pulmonary edema (HAPE). Of these, HAPE is highly correlated with acute pulmonary hypertension. The first chronic syndrome described in HA dwellers in Peru was chronic mountain sickness (Monge disease), which has a large component of relative hypoventilation and secondary erythrocytosis. The prevalence of chronic mountain sickness in HA dwellers ranges from 1.2% in native Tibetans to 5.6% in Chinese Han; 6% to 8% in male residents of La Paz, Bolivia; and 15.6% in the Andes. Subacute mountain sickness is an exaggerated pulmonary hypertensive response to HA hypoxia occurring over months, most often in infants and very young children. Chronic pulmonary hypertension with heart failure but without hypoventilation is seen in Asia. Not only does HA pulmonary hypertension exact health consequences for the millions affected, but also the mechanisms of disease relate to pulmonary hypertension associated with multiple other disorders. Genetic understanding of these disorders is in its infancy.

Respiratory effects of changing the volume load imposed on the peripheral venous system

This study was designed to determine if acute distension of the hindlimb venous circulation stimulates breathing, thereby contributing to the respiratory responses to rapid changes in total blood volume. In 10 spontaneously breathing anesthetized sheep, we withdrew 15 ml kg(-1) of blood from a femoral vein over approximately 1-2 min. We then compared the respiratory effects of infusing this venous blood back into the femoral veins across two conditions: the inferior vena cava (IVC) was either unobstructed or obstructed by a balloon-tipped catheter. We found that when blood was withdrawn and blood volume decreased, an absolute increase in breathing often occurred, but more importantly that a relative hyperventilation was always observed. When this blood was re-infused into the animal, effectively increasing blood volume, the respiratory response depended upon whether or not the IVC was open or obstructed. With the IVC unobstructed, a relative hypoventilation occurred, accompanied by an increase in alveolar PCO(2). In contrast, when the venous blood was re-infused and the IVC was obstructed, ventilation increased significantly, and the response was often hypocapnic. These results indicate that increasing the volume load in the venous circulation increases breathing, and that the transduction mechanism is contained within the peripheral venous system. Further, the respiratory drive from this sensory mechanism is subject to modulation via changes in the circulatory status, most likely within the arterial side.

Effect of menopause on the chemical control of breathing and its relationship with acid-base status

This study examined the role of alterations in the chemoreflex control of breathing, acid-base balance, and their interaction in postmenopausal ventilatory adaptations. A modified iso-oxic hyperoxic and hypoxic CO(2)-rebreathing procedure was employed to evaluate central and peripheral chemoreflex drives to breathe, respectively, in 15 healthy postmenopausal and 20 premenopausal women of similar age. Arterialized venous blood samples were collected at rest for the estimation of arterial Pco(2) (Pa(CO(2))) and H(+) concentration ([H(+)]), plasma strong ion difference ([SID]) and total weak acid ([A](tot)) concentrations, and serum progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) concentrations. In post- compared with premenopausal women, Pa(CO(2)), [SID], and the central chemoreflex ventilatory recruitment threshold for Pco(2) (VRTco(2)) were higher, whereas [P(4)] and [E(2)] were lower (all P < 0.05), with no significant change in central or peripheral chemoreflex sensitivity, peripheral chemoreflex VRTco(2), and [A](tot). The acidifying effect of an increased Pa(CO(2)) was offset by the alkalizing effect of an increased [SID], such that [H(+)] was preserved in post- compared with premenopausal women. Pa(CO(2)) correlated positively with the central chemoreflex VRTco(2) (r = 0.67, P < 0.01), which in turn correlated positively with [SID] (r = 0.53, P < 0.01) within the pooled data. In conclusion, the relative alveolar hypoventilation and attendant arterial hypercapnia in healthy post- compared with premenopausal women could be explained, in part, by the interaction of 1) reduced central, but not peripheral, chemoreflex VRTco(2), 2) increased [SID], and 3) reduced circulating female sex steroid hormone concentrations.

Pulmonary gas exchange in diving

Diving-related pulmonary effects are due mostly to increased gas density, immersion-related increase in pulmonary blood volume, and (usually) a higher inspired Po(2). Higher gas density produces an increase in airways resistance and work of breathing, and a reduced maximum breathing capacity. An additional mechanical load is due to immersion, which can impose a static transrespiratory pressure load as well as a decrease in pulmonary compliance. The combination of resistive and elastic loads is largely responsible for the reduction in ventilation during underwater exercise. Additionally, there is a density-related increase in dead space/tidal volume ratio (Vd/Vt), possibly due to impairment of intrapulmonary gas phase diffusion and distribution of ventilation. The net result of relative hypoventilation and increased Vd/Vt is hypercapnia. The effect of high inspired Po(2) and inert gas narcosis on respiratory drive appear to be minimal. Exchange of oxygen by the lung is not impaired, at least up to a gas density of 25 g/l. There are few effects of pressure per se, other than a reduction in the P50 of hemoglobin, probably due to either a conformational change or an effect of inert gas binding.

Exercise-induced arterial hypoxaemia in active young women

Studies examining pulmonary gas exchange during exercise have primarily focused on young healthy men, whereas the female response to exercise has received limited attention. Evidence is accumulating that the response of the lungs, airways, and (or) respiratory muscles to exercise is less than ideal and this may significantly compromise oxygen transport in certain groups of otherwise healthy, fit, active, male subjects. Women may be even more susceptible to exercise-induced pulmonary limitations than height-matched men, by virtue of their smaller lung volumes, lower maximal expiratory flow rates, and smaller diffusion surface areas. We have recently shown that exercise-induced arterial hypoxaemia (EIAH) is more prevalent and occurs at relatively lower fitness levels in females than in males. Despite this finding, few physiologically based mechanisms have been identified to explain why women may be more susceptible to EIAH than men. Potential mechanisms of EIAH include relative alveolar hypoventilation, ventilation-perfusion inequality, and diffusion limitation. Whether these mechanisms are different between sexes remains controversial. The primary purpose of this review is to summarize the available data on EIAH in women and to discuss potential sex-based mechanisms for gas exchange impairment. Furthermore, we discuss unresolved questions dealing with pulmonary system limitations during exercise in women.

Determinants of maximal oxygen uptake in moderate acute hypoxia in endurance athletes

The factors determining maximal oxygen consumption were explored in eight endurance trained subjects (TS) and eight untrained subjects (US) exposed to moderate acute normobaric hypoxia. Subjects performed maximal incremental tests at sea level and simulated altitudes (1,000, 2,500, 4,500 m). Heart rate (HR), stroke volume (SV), cardiac output (.Q), arterialized oxygen saturation (Sa'O2), oxygen uptake (.VO2max), ventilation (.VE, expressed in normobaric conditions) were measured. At maximal exercise, ventilatory equivalent (.VE/.VO2max), O2 transport (.QaO2max) and O2 extraction (O2ERmax) were calculated. In TS, .Qmax remained unchanged despite a significant reduction in HRmax at 4,500 m. SVmax remained unchanged. .VEmax decreased in TS at 4,500 m, .VE/.VO2max was lower in TS and greater at 4,500 m vs. sea level in both groups. Sa'O2max decreased at and above 1,000 m in TS and 2,500 m in US, O2ERmax increased at 4,500 m in both groups. .QaO2max decreased with altitude and was greater in TS than US up to 2,500 m but not at 4,500 m. .VO2max decreased with altitude but the decrement (Delta.VO2max) was larger in TS at 4,500 m. In both groups Delta.VO2max in moderate hypoxia was correlated with Delta.QaO2max. Several differences between the two groups are probably responsible for the greater Delta.VO2max in TS at 4,500 m : (1) the relative hypoventilation in TS as shown by the decrement in .VEmax at 4,500 m (2) the greater.QaO2max decrement in TS due to a lower Sa'O2max and unchanged .Qmax 3) the smaller increase in O2ERmax in TS, insufficient to compensate the decrease in .QaO2max.

Moderate exercise in hypoxia induces a greater arterial desaturation in trained than untrained men

During moderate exercise breathing a low inspired O(2) fraction (F(I)O(2)), arterial O(2) desaturation may depend on the fitness level. Seven trained (TM) and seven untrained men (UTM) cycled in normoxia and in hypoxia (F(I)O(2)=0.187, 0.173, 0.154, 0.13 and 0.117). We compared TM and UTM at submaximal intensities below the ventilatory threshold. Ventilatory variables were monitored and arterial oxygen saturation was measured by pulse oximetry. O(2) saturation was not different between groups at sea level. In hypoxia, O(2) saturation was lower in TM than in UTM at F(I)O(2)=0.154 (87.3 +/- 2.9% vs 90.4 +/- 1.5% at 90 W) and below. Both the ventilatory-equivalent and the end-tidal O(2) pressure were lower in TM at sea level and at every F(I)O(2), with the differences between TM and UTM becoming apparent at lower exercise intensity and increasing in magnitude as the severity of hypoxia increased. O(2) saturation was correlated with the ventilatory parameters at every F(I)O(2) and the correlations were stronger in severe hypoxia. These results demonstrate that a moderate exercise carried out in hypoxia, contrary to normoxic conditions, can lead to a greater arterial desaturation in TM compared with UTM. This phenomenon could be partly attributed to a relative hypoventilation in trained subjects.

Arterial acid–base status during digestion and following vascular infusion of NaHCO 3 and HCl in the South American rattlesnake, Crotalus durissus

Digestion is associated with gastric secretion that leads to an alkalinisation of the blood, termed the “alkaline tide”. Numerous studies on different reptiles and amphibians show that while plasma bicarbonate concentration ([HCO 3 −] pl) increases substantially during digestion, arterial pH (pHa) remains virtually unchanged, due to a concurrent rise in arterial PCO 2 (PaCO 2) caused by a relative hypoventilation. This has led to the suggestion that postprandial amphibians and reptiles regulate pHa rather than PaCO 2. Here we characterize blood gases in the South American rattlesnake ( Crotalus durissus) during digestion and following systemic infusions of NaHCO 3 and HCl in fasting animals to induce a metabolic alkalosis or acidosis in fasting animals. The magnitude of these acid–base disturbances were similar in magnitude to that mediated by digestion and exercise. Plasma [HCO 3 −] increased from 18.4 ± 1.5 to 23.7 ± 1.0 mmol L − 1 during digestion and was accompanied by a respiratory compensation where PaCO 2 increased from 13.0 ± 0.7 to 19.1 ± 1.4 mm Hg at 24 h. As a result, pHa decreased slightly, but were significantly below fasting levels 36 h into digestion. Infusion of NaHCO 3 (7 mmol kg − 1 ) resulted in a 10 mmol L − 1 increase in plasma [HCO 3 −] within 1 h and was accompanied by a rapid elevation of pHa (from 7.58 ± 0.01 to 7.78 ± 0.02). PaCO 2, however, did not change following HCO 3 − infusion, which indicates a lack of respiratory compensation. Following infusion of HCl (4 mmol kg − 1 ), plasma pHa decreased by 0.07 units and [HCO 3 −] pl was reduced by 4.6 mmol L − 1 within the first 3 h. PaCO 2, however, was not affected and there was no evidence for respiratory compensation. Our data show that digesting rattlesnakes exhibit respiratory compensations to the alkaline tide, whereas artificially induced metabolic acid–base disturbances of same magnitude remain uncompensated. It seems difficult to envision that the central and peripheral chemoreceptors would experience different stimuli during these conditions. One explanation for the different ventilatory responses could be that digestion induces a more relaxed state with low responsiveness to ventilatory stimuli.

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

Post-hyperventilation hypoxaemia is due to alteration of ventilation and perfusion matching.

The aim of this study was to investigate the mechanisms of post-hyperventilation hypoxia. Seven healthy male volunteers, aged 29.1 +/- 1.4 years, underwent two 10-min periods of voluntary hyperventilation to pulmonary end tidal CO2 values of 20 mmHg (severe hyperventilation), or 30 mmHg (moderate hyperventilation). Post-hyperventilation, the arterial oxygen saturation, VE and arterial blood gas values were measured. Sleep was excluded by EEG monitoring. Maximal hypoxaemia occurred in proportion to severity of hyperventilation; at approximately 5 min post-hyperventilation Pao2 fell to 64 +/- 7 mmHg (severe hyperventilation) and 72 +/- 6 mmHg (moderate hyperventilation) from 97 +/- 3 mmHg at baseline. Hypoxaemia persisted beyond the time of normalization of Paco2 and HCO3. On another occasion, a N2 washout test was performed after severe hyperventilation, which excluded bronchoconstriction. Relative hypoventilation may partly explain post-hyperventilation hypoxaemia, but by excluding bronchoconstriction and periodic breathing, we have demonstrated that most of the hypoxaemia must have been due to alteration of pulmonary blood flow distribution causing a fall in V/Q ratio.

Principles of artificial ventilation

Ventilators are used commonly in the operating theatre and in the ICU to deliver mechanical ventilation to the lungs. In the operating theatre, ventilation is in anaesthetized and often pharmacologically paralysed patients with predominantly normal lungs. These ventilators are relatively simple and are designed to deliver varying concentrations of oxygen, air, nitrous oxide and volatile agents to patients through an anaesthetic circuit. In the ICU, ventilators provide respiratory support to patients with respiratory failure. Respiratory failure is a state in which the pulmonary oxygen uptake is so severely disturbed that the supply of oxygen to the tissues and/or the removal of carbon dioxide from them is inadequate. Respiratory failure can be caused by relative hypoventilation, characterized by an increase in arterial carbon dioxide tension, or failure of diffusion at the alveolar-capillary membrane, characterized by decreased arterial oxygen tension.

Effects of inhibition gastric acid secretion on arterial acid–base status during digestion in the toad Bufo marinus

Digestion affects acid–base status, because the net transfer of HCl from the blood to the stomach lumen leads to an increase in HCO 3 − levels in both extra- and intracellular compartments. The increase in plasma [HCO 3 −], the alkaline tide, is particularly pronounced in amphibians and reptiles, but is not associated with an increased arterial pH, because of a concomitant rise in arterial P co 2 caused by a relative hypoventilation. In this study, we investigate whether the postprandial increase in Pa co 2 of the toad Bufo marinus represents a compensatory response to the increased plasma [HCO 3 −] or a state-dependent change in the control of pulmonary ventilation. To this end, we successfully prevented the alkaline tide, by inhibiting gastric acid secretion with omeprazole, and compared the response to that of untreated toads determined in our laboratory during the same period. In addition, we used vascular infusions of bicarbonate to mimic the alkaline tide in fasting animals. Omeprazole did not affect blood gases, acid–base and haematological parameters in fasting toads, but abolished the postprandial increase in plasma [HCO 3 −] and the rise in arterial P co 2 that normally peaks 48 h into the digestive period. Vascular infusion of HCO 3 −, that mimicked the postprandial rise in plasma [HCO 3 −], led to a progressive respiratory compensation of arterial pH through increased arterial P co 2. Thus, irrespective of whether the metabolic alkalosis is caused by gastric acid secretion in response to a meal or experimental infusion of bicarbonate, arterial pH is being maintained by an increased arterial P co 2. It seems, therefore, that the elevated P co 2, occuring during the postprandial period, constitutes of a regulated response to maintain pH rather than a state-dependent change in ventilatory control.