Ventilation-perfusion Inequality Research Articles

Hemorrhagic Shock: Blood Marker Sequencing and Pulmonary Gas Exchange

The early identification of internal hemorrhage in critically ill patients may be difficult. Besides circulatory parameters, hemoglobin and lactate concentration, metabolic acidosis and hyperglycemia serve as laboratory markers for bleeding. In this experiment, we examined pulmonary gas exchange in a porcine model of hemorrhagic shock. Moreover, we sought to investigate if a chronological order of appearance regarding hemoglobin, lactatemia, standard base excess/deficit (SBED) and hyperglycemia exists in early severe hemorrhage. In this prospective, laboratory study, twelve anesthetized pigs were randomly allocated to exsanguination or a control group. Animals in the exsanguination group (n = 6) endured a 65% blood loss over 20 min. No intravenous fluids were administered. Measurements were taken before, immediately after, and at 60 min after the completed exsanguination. Measurements included pulmonary and systemic hemodynamic variables, hemoglobin concentration, lactate, base excess (SBED), glucose concentration, arterial blood gases, and a multiple inert gas assessment of pulmonary function. At baseline, variables were comparable. Immediately after exsanguination, lactate and blood glucose were increased (p = 0.001). The arterial partial pressure of oxygen was increased at 60 min after exsanguination (p = 0.04) owing to a decrease in intrapulmonary right-to-left shunt and less ventilation-perfusion inequality. SBED was different to the control only at 60 min post bleeding (p < 0.001). Hemoglobin concentration did not change at any time (p = 0.97 and p = 0.14). In experimental shock, markers of blood loss became positive in chronological order: lactate and blood glucose concentrations were raised immediately after blood loss, while changes in SBED lagged behind and became significant one hour later. Pulmonary gas exchange is improved in shock.

The impact of ventilation-perfusion inequality in COVID-19: a computational model.

COVID-19 infection may lead to acute respiratory distress syndrome (CARDS) where severe gas exchange derangements may be associated, at least in the early stages, only with minor pulmonary infiltrates. This may suggest that the shunt associated to the gasless lung parenchyma is not sufficient to explain CARDS hypoxemia. We designed an algorithm (VentriQlar), based on the same conceptual grounds described by J.B. West in 1969. We set 498 ventilation–perfusion (VA/Q) compartments and, after calculating their blood composition (PO2, PCO2, and pH), we randomly chose 106 combinations of five parameters controlling a bimodal distribution of blood flow. The solutions were accepted if the predicted PaO2 and PaCO2 were within 10% of the patient’s values. We assumed that the shunt fraction equaled the fraction of non-aerated lung tissue at the CT quantitative analysis. Five critically-ill patients later deceased were studied. The PaO2/FiO2 was 91.1 ± 18.6 mmHg and PaCO2 69.0 ± 16.1 mmHg. Cardiac output was 9.58 ± 0.99 L/min. The fraction of non-aerated tissue was 0.33 ± 0.06. The model showed that a large fraction of the blood flow was likely distributed in regions with very low VA/Q (Qmean = 0.06 ± 0.02) and a smaller fraction in regions with moderately high VA/Q. Overall LogSD, Q was 1.66 ± 0.14, suggestive of high VA/Q inequality. Our data suggest that shunt alone cannot completely account for the observed hypoxemia and a significant VA/Q inequality must be present in COVID-19. The high cardiac output and the extensive microthrombosis later found in the autopsy further support the hypothesis of a pathological perfusion of non/poorly ventilated lung tissue.NEW & NOTEWORTHY Hypothesizing that the non-aerated lung fraction as evaluated by the quantitative analysis of the lung computed tomography (CT) equals shunt (VA/Q = 0), we used a computational approach to estimate the magnitude of the ventilation–perfusion inequality in severe COVID-19. The results show that a severe hyperperfusion of poorly ventilated lung region is likely the cause of the observed hypoxemia. The extensive microthrombosis or abnormal vasodilation of the pulmonary circulation may represent the pathophysiological mechanism of such VA/Q distribution.

Measuring the efficiency of pulmonary gas exchange using expired gas instead of arterial blood: comparing the "ideal" Po2 of Riley with end-tidal Po2.

When using a new noninvasive method for measuring the efficiency of pulmonary gas exchange, a key measurement is the oxygen deficit, defined as the difference between the end-tidal alveolar Po2 and the calculated arterial Po2. The end-tidal Po2 is measured using a rapid gas analyzer, and the arterial Po2 is derived from pulse oximetry after allowing for the effect of the Pco2 on the oxygen affinity of hemoglobin. In the present report we show that the values of end-tidal Po2 and Pco2 are highly reproducible, providing a solid foundation for the measurement of the oxygen deficit. We compare the oxygen deficit with the classical ideal alveolar-arterial Po2 difference (A-aDO2) as originally proposed by Riley, and now extensively used in clinical practice. This assumes Riley's criteria for ideal alveolar gas, namely no ventilation-perfusion inequality, the same Pco2 as arterial blood, and the same respiratory exchange ratio as the whole lung. It transpires that, in normal subjects, the end-tidal Po2 is essentially the same as the ideal value. This conclusion is consistent with the very small oxygen deficit that we have reported in young normal subjects, the significantly higher values seen in older normal subjects, and the much larger values in patients with lung disease. We conclude that this noninvasive measurement of the efficiency of pulmonary exchange is identical in many respects to that based on the ideal alveolar Po2, but that it is easier to obtain.

Early and late effects of remote ischemic preconditioning on spirometry and gas exchange in healthy volunteers

PurposeRemote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol. Results60 min after RIP capillary pO2 decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO2, variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups. ConclusionOxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.

Effect of net gas volume changes on alveolar and arterial gas partial pressures in the presence of ventilation-perfusion mismatch.

The second gas effect (SGE) occurs when nitrous oxide enhances the uptake of volatile anesthetics administered simultaneously. Recent work shows that the SGE is greater in blood than in the gas phase, that this is due to ventilation-perfusion mismatch, that as mismatch increases, the SGE increases in blood but is diminished in the gas phase, and that these effects persist well into the period of nitrous oxide maintenance anesthesia. These modifications of the SGE are most pronounced with the low soluble agents in current use. We investigate further the effect of net gas volume loss during nitrous oxide uptake on low concentrations of other gases present using partial pressure-solubility diagrams. The steady-state equations of gas exchange were solved assuming a log-normal distribution of ventilation-perfusion ratios using Lebesgue-Stieltjes integration. It was shown that under these conditions the classical partial pressure-solubility diagram must be modified, that for currently used volatile anesthetic agents the alveolar-arterial partial pressure difference is less than that predicted in the past, and that the alveolar-arterial partial pressure difference may even be reversed during uptake in the case of highly insoluble gases such as sulfur hexafluoride. Comparing this with the situation described previously for nitrogen in steady-state air breathing, we show that for nitrogen, the direction of the alveolar-arterial gradient is opposite to the direction of net gas volume movement. Although gas uptake with ventilation-perfusion inequality exceeding that when matching is optimal is shown to be possible, it is less likely than alveolar-arterial partial pressure reversal. NEW & NOTEWORTHY Net uptake of gases administered with nitrous oxide may proceed against an alveolar-arterial partial pressure gradient. The alveolar-arterial gradient for nitrogen in the steady-state breathing air depends not only on the existence of a distribution of ventilation-perfusion ratios in the lung but also on the presence of a net change in gas volume and is opposite in direction to the direction of net gas volume uptake.

The thoracic shape of hominoids.

In hominoids, the broad thorax has been assumed to contribute to their dorsal scapular position. However, the dorsoventral diameter of their cranial thorax was found in one study to be longer in hominoids. There are insufficient data on thoracic shape to explain the relationship between broad thorax and dorsal scapular position. The current study presents data on multilevel cross-sectional shape and volume distribution in a range of primates. Biplanar radiographs of intact fluid-preserved cadavers were taken to measure the cross-sectional shape of ten equally spaced levels through the sternum (called decisternal levels) and the relative volume of the nine intervening thoracic segments. It was found that the cranial thorax of hominoids is larger and broader (except in the first two decisternal levels) than that of other primates. The cranial thorax of hominoids has a longer dorsoventral diameter because the increase in dorsoventral diameter caused by the increase in the volume of the cranial thorax overcompensates for the decrease caused by the broadening of the cranial thorax. The larger and broader cranial thorax in hominoids can be explained as a locomotor adaptation for scapular gliding and as a respiratory adaptation for reducing the effects of orthograde posture on ventilation-perfusion inequality.

Increased cardiac output, not pulmonary artery systolic pressure, increases blood flow through intrapulmonary arteriovenous anastomoses and impairs pulmonary gas exchange efficiency (717.2)

Sources of venous admixture (QVA/QT) that impair pulmonary gas exchange efficiency, defined by an increased alveolar‐arterial PO2 difference (AaDO2), are ventilation‐perfusion inequality (VA/Q), diffusion limitation, and shunt. Blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) increases QVA/QT and the AaDO2. However, it is unclear whether increased cardiac output (QT) or pulmonary artery systolic pressure (PASP) cause the increase in QIPAVA. We hypothesized that an increase in QT alone would increase QIPAVA resulting in an increased AaDO2 at rest breathing room air and 40% O2 to prevent contributions from diffusion and VA/Q. Epinephrine, i.v. at 320 ng/kg/min (EPI), and low dose epinephrine (80 ng/kg/min) combined with 2 mg of atropine (EPI+ATR) were used in healthy human subjects (n=5) to increase QT. When breathing either room air or 40% O2, EPI and EPI+ATR increased QT, (measured by acetylene uptake) from 7.8±1.0 to 13.3±3.4 L/min. Only EPI significantly increased PASP (to 54±14 mmHg), measured with ultrasound, but not with EPI+ATR (to 39±5 mmHg). However, EPI and EPI+ATR, breathing either room air or 40% O2 resulted in equal QIPAVA detected with saline contrast echocardiography. Furthermore, with EPI and EPI+ATR, the AaDO2 increased significantly when breathing either room air or 40% O2. Consistent with our data above, the calculated QVA/QT required to account for the entire AaDO2 was 2.4±0.4% with EPI and EPI+ATR, breathing either room air or 40% O2. We conclude that increased QT alone significantly increases QIPAVA and AaDO2 in healthy humans.Grant Funding Source: Supported by: Department of Defense #W81XWH‐10‐2‐0114, AHA Predoctoral Fellowship

Phenylephrine to Treat Hypoxemia during One-Lung Ventilation in a Pediatric Patient.

To improve surgical visualization and facilitate the procedure, one-lung ventilation (OLV) is frequently used during thoracic surgery. Although generally well tolerated, the ventilation–perfusion inequality induced by OLV may lead to a decrease in oxygenation and, at times, hypoxemia. Effective treatment algorithms and strategies are necessary for the treatment of hypoxemia during OLV to ensure that the technique can be continued without interruption and allow for completion of the surgical procedure. Treatment strategies may include applying positive end expiratory pressure to the nonoperative lung, continuous positive airway pressure or low flow oxygen insufflation to the operative lung, decreasing anesthetic agents that interfere with hypoxic pulmonary vasoconstriction (HPV), or switching to total intravenous anesthesia. Although less commonly employed, α-adrenergic agonists may also improve oxygenation during OLV by augmenting HPV. We present a 12-year-old girl who developed hypoxemia during OLV, which was not corrected by the usual maneuvers. Hypoxemia was successfully treated with a phenylephrine infusion. The potential applications of α-adrenergic agonists such as phenylephrine in the treatment of hypoxemia during OLV are discussed and its physiologic basis reviewed.

Improving the survival and growth of African catfish (Clarias gariepinus) fingerlings by using Nile tilapi

General anaesthesia and many types of acute respiratory failure are accompanied by a decrease in functional residual capacity (FRC). This reduction promotes closure of dependent airways and alveolar collapse, thus impeding ventilation of these regions. Perfusion, on the other hand, is forced towards dependent regions by lowered pulmonary vascular pressure and increased alveolar pressure. Ventilation-perfusion (V/Q) inequality develops, impairing gas exchange and arterial oxygenation. Application of general positive end-expiratory pressure (PEEP) increases FRC and may improve gas exchange but cannot restore V/Q to normal. Differential ventilation, with equal distribution of ventilation between the lungs, and the application of PEEP solely to the dependent lung (selective PEEP) with the patient in the lateral position, improve V/Q matching and gas exchange with less impedance of cardiac output and less danger of barotrauma. This ventilation technique has proved successful in short-term experiments and in a small number of patients treated over several days.

Mechanisms of gas exchange response to lung volume reduction surgery in severe emphysema

Lung volume reduction surgery (LVRS) improves lung function, respiratory symptoms, and exercise tolerance in selected patients with chronic obstructive pulmonary disease, who have heterogeneous emphysema. However, the reported effects of LVRS on gas exchange are variable, even when lung function is improved. To clarify how LVRS affects gas exchange in chronic obstructive pulmonary disease, 23 patients were studied before LVRS, 14 of whom were again studied afterwards. We performed measurements of lung mechanics, pulmonary hemodynamics, and ventilation-perfusion (Va/Q) inequality using the multiple inert-gas elimination technique. LVRS improved arterial Po₂ (Pa(O₂)) by a mean of 6 Torr (P = 0.04), with no significant effect on arterial Pco₂ (Pa(CO₂)), but with great variability in both. Lung mechanical properties improved considerably more than did gas exchange. Post-LVRS Pa(O₂) depended mostly on its pre-LVRS value, whereas improvement in Pa(O(2)) was explained mostly by improved Va/Q inequality, with lesser contributions from both increased ventilation and higher mixed venous Po(2). However, no index of lung mechanical properties correlated with Pa(O₂). Conversely, post-LVRS Pa(CO₂) bore no relationship to its pre-LVRS value, whereas changes in Pa(CO₂) were tightly related (r² = 0.96) to variables, reflecting decrease in static lung hyperinflation (intrinsic positive end-expiratory pressure and residual volume/total lung capacity) and increase in airflow potential (tidal volume and maximal inspiratory pressure), but not to Va/Q distribution changes. Individual gas exchange responses to LVRS vary greatly, but can be explained by changes in combinations of determining variables that are different for oxygen and carbon dioxide.

Respiratory changes with seizures in localization‐related epilepsy: Analysis of periictal hypercapnia and airflow patterns

The rate of sudden unexpected death in epilepsy (SUDEP) approaches 9 per 1,000 patient-years in patients with refractory epilepsy. Respiratory causes are implicated in SUDEP. We reported that ictal hypoxemia occurs in one-third of seizures in localization-related epilepsy. We now report on respiratory changes in the ictal/postictal period including changes in end-tidal CO₂ (ETCO₂) that correlate directly with alveolar CO(2) , allowing a precise evaluation of seizure-related respiratory disturbances. One hundred eighty-seven seizures were recorded in 33 patients with localization-related epilepsy, with or without secondarily generalized convulsions, undergoing video-electroencephalography (EEG) telemetry with recording of respiratory data. The ictal/postictal ETCO₂ increase from baseline was 14 ± 11 mm Hg (11, -1 to 50) [mean ± standard deviation (SD) (median, range)]. ETCO₂ peak was at or above 50 mm Hg with 35 of 94 seizures, 60 mm Hg with 15, and 70 mm Hg with five seizures. Eleven of the 33 patients had seizures with ETCO₂ elevation above 50 mm Hg. The duration of ictal/postictal ETCO(2) increase above baseline was 424 ± 807 s (154, 4 to 6225). The duration of ictal apnea was 49 ± 46 s (31, 6-222); most ictal apneic events were central. Oxygen desaturation to 60% or less occurred with 10 seizures, including five that did not progress to generalized convulsions. Respiratory rate and amplitude increased postictally. The peak ictal ETCO₂ change and duration of change were not associated with apnea duration or seizure duration. Peak ETCO₂ change was significantly associated with contralateral seizure spread. Severe and prolonged increases in ETCO₂ occur with seizures. Postictally, respiratory effort is not impaired. Ictally triggered ventilation-perfusion inequality from pulmonary shunting or transient neurogenic pulmonary edema may account for these findings.

Operation Everest II

In October 1985, 25 years ago, 8 subjects and 27 investigators met at the United States Army Research Institute for Environmental Medicine (USARIEM) altitude chambers in Natick, Massachusetts, to study human responses to a simulated 40-day ascent of Mt. Everest, termed Operation Everest II (OE II). Led by Charlie Houston, John Sutton, and Allen Cymerman, these investigators conducted a large number of investigations across several organ systems as the subjects were gradually decompressed over 40 days to the Everest summit equivalent. There the subjects reached a V(O)(2)max of 15.3 mL/kg/min (28% of initial sea-level values) at 100 W and arterial P(O(2)) and P(CO(2)) of approximately 28 and approximately 10 mm Hg, respectively. Cardiac function resisted hypoxia, but the lungs could not: ventilation-perfusion inequality and O(2) diffusion limitation reduced arterial oxygenation considerably. Pulmonary vascular resistance was increased, was not reversible after short-term hyperoxia, but was reduced during exercise. Skeletal muscle atrophy occurred, but muscle structure and function were otherwise remarkably unaffected. Neurological deficits (cognition and memory) persisted after return to sea level, more so in those with high hypoxic ventilatory responsiveness, with motor function essentially spared. Nine percent body weight loss (despite an unrestricted diet) was mainly (67%) from muscle and exceeded the 2% predicted from energy intake-expenditure balance. Some immunological and lipid metabolic changes occurred, of uncertain mechanism or significance. OE II was unique in the diversity and complexity of studies carried out on a single, courageous cohort of subjects. These studies could never have been carried out in the field, and thus complement studies such as the American Medical Research Expedition to Everest (AMREE) that, although more limited in scope, serve as benchmarks and reality checks for chamber studies like OE II.

Physiology of obesity and effects on lung function

In obese people, the presence of adipose tissue around the rib cage and abdomen and in the visceral cavity loads the chest wall and reduces functional residual capacity (FRC). The reduction in FRC and in expiratory reserve volume is detectable, even at a modest increase in weight. However, obesity has little direct effect on airway caliber. Spirometric variables decrease in proportion to lung volumes, but are rarely below the normal range, even in the extremely obese, while reductions in expiratory flows and increases in airway resistance are largely normalized by adjusting for lung volumes. Nevertheless, the reduction in FRC has consequences for other aspects of lung function. A low FRC increases the risk of both expiratory flow limitation and airway closure. Marked reductions in expiratory reserve volume may lead to abnormalities in ventilation distribution, with closure of airways in the dependent zones of the lung and ventilation perfusion inequalities. Greater airway closure during tidal breathing is associated with lower arterial oxygen saturation in some subjects, even though lung CO-diffusing capacity is normal or increased in the obese. Bronchoconstriction has the potential to enhance the effects of obesity on airway closure and thus on ventilation distribution. Thus obesity has effects on lung function that can reduce respiratory well-being, even in the absence of specific respiratory disease, and may also exaggerate the effects of existing airway disease.

Ventilation-perfusion inequality in the human lung is not increased following no-decompression-stop hyperbaric exposure

Venous gas bubbles occur in recreational SCUBA divers in the absence of decompression sickness, forming venous gas emboli (VGE) which are trapped within pulmonary circulation and cleared by the lung without overt pathology. We hypothesized that asymptomatic VGE would transiently increase ventilation-perfusion mismatch due to their occlusive effects within the pulmonary circulation. Two sets of healthy volunteers (n = 11, n = 12) were recruited to test this hypothesis with a single recreational ocean dive or a baro-equivalent dry hyperbaric dive. Pulmonary studies (intrabreath V A/Q (iV/Q), alveolar dead space, and FVC) were conducted at baseline and repeat 1- and 24-h after the exposure. Contrary to our hypothesis V A/Q mismatch was decreased 1-h post-SCUBA dive (iV/Q slope 0.023 ± 0.008 ml−1 at baseline vs. 0.010 ± 0.005 NS), and was significantly reduced 24-h post-SCUBA dive (0.000 ± 0.005, p < 0.05), with improved V A/Q homogeneity inversely correlated to dive severity. No changes in V A/Q mismatch were observed after the chamber dive. Alveolar dead space decreased 24-h post-SCUBA dive (78 ± 10 ml at baseline vs. 56 ± 5, p < 0.05), but not 1-h post dive. FVC rose 1-h post-SCUBA dive (5.01 ± 0.18 l vs. 5.21 ± 0.26, p < 0.05), remained elevated 24-h post SCUBA dive (5.06 ± 0.2, p < 0.05), but was decreased 1-hr after the chamber dive (4.96 ± 0.31 L to 4.87 ± 0.32, p < 0.05). The degree of V A/Q mismatch in the lung was decreased following recreational ocean dives, and was unchanged following an equivalent air chamber dive, arguing against an impact of VGE on the pulmonary circulation.

Transcutaneous carbon dioxide monitoring in infants and children

To review the technology required for and the applications of transcutaneous carbon dioxide (TC-CO2) monitoring in infants and children. A computerized, bibliographic search regarding the applications of transcutaneous carbon dioxide (TC-CO2) monitoring in infants and children. Although the direct measurement of P(a)CO2 remains the gold standard, it provides only a single measurement of what is often a rapidly changing and evolving clinical picture. Given these concerns, there remains a clinical need for a means to continuously monitor P(a)CO2 without the need for repeated blood gas analysis. Although initially introduced into the neonatal intensive care unit; with improvements in the technology, TC-CO2 monitoring can now be used in infants, children and even adults. When compared with end-tidal carbon dioxide (ET-CO2) monitoring techniques, TC-CO2 monitoring has been shown to be equally as accurate in patients with normal respiratory function and more accurate in patients with shunt or ventilation-perfusion inequalities. TC-CO2 monitoring can be applied in situations that generally preclude ET-CO2 monitoring such as high frequency ventilation, apnea testing, and noninvasive ventilation. TC-CO2 monitoring has also been used in spontaneously breathing children with airway and respiratory issues such as croup and status asthmaticus as well as to monitor metabolic status during treatment of acidosis related to diabetic ketoacidosis. Transcutaneous carbon dioxide monitoring may be a useful adjunct in various clinical scenarios in infants and children. It should be viewed as a complimentary technology and may be used in combination with ET-CO2 monitoring.

Point:Counterpoint: Exercise-induced intrapulmonary shunting is imaginary vs. real

Pulmonary gas exchange efficiency deteriorates with exercise in both humans and other species, increasing the alveolar-arterial PO2 difference (AaDO2) ([2][1]). The potential contributors to this are ventilation-perfusion inequality, alveolar-capillary diffusion limitation, and shunt ([20][2]).

Is pulmonary gas exchange during exercise in hypoxia impaired with the increase of cardiac output?

During exercise in humans, the alveolar-arterial O(2) tension difference ((A-a)DO(2)) increases with exercise intensity and is an important factor determining the absolute level of oxygen binding to hemoglobin and therefore the level of systemic oxygen transport. During exercise in hypoxia, the (A-a)DO(2) is accentuated. Using the multiple inert gas elimination technique it has been shown that during exercise in acute hypoxia the contribution of ventilation-perfusion inequality to (A-a)DO(2) is rather small and in the absence of pulmonary edema intrapulmonary shunts can be ruled out. This implies that the main mechanism limiting pulmonary gas exchange is diffusion limitation. It is presumed that an elevation of cardiac output during exercise in acute hypoxia should increase the (A-a)DO(2). However, no studies have examined how variations in cardiac output independently affect pulmonary diffusion with increases in exercise intensity. We have consistently observed that during steady-state, submaximal (100-120 W) exercise on the cycle ergometer in hypoxia the lung can accommodate an increase in cardiac output of approximately 2 L x min(-1) without any significant effect on pulmonary gas exchange. This result contrasts with the predicted effect of cardiac output on (A-a)DO(2) using the model of Piiper and Scheid, and thus indicates that an elevation of cardiac output is not necessarily accompanied by a reduction of mean transit time and (or) diffusion limitation during submaximal exercise in acute hypoxia. It remains to be determined what is the influence of changes in cardiac output per se on pulmonary gas exchange during high-intensity exercise.

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.

The canine spleen in oxygen transport: gas exchange and hemodynamic responses to splenectomy

In athletic animals the spleen induces acute polycythemia by dynamic contraction that releases red blood cells into the circulation in response to increased O(2) demand and metabolic stress; when energy demand is relieved, the polycythemia is rapidly reversed by splenic relaxation. We have shown in adult foxhounds that splenectomy eliminates exercise-induced polycythemia, thereby reducing peak O(2) uptake and lung diffusing capacity for carbon monoxide (DL(CO)) as well as exaggerating preexisting DL(CO) impairment imposed by pneumonectomy (Dane DM, Hsia CC, Wu EY, Hogg RT, Hogg DC, Estrera AS, Johnson RL Jr. J Appl Physiol 101: 289-297, 2006). To examine whether the postsplenectomy reduction in DL(CO) leads to abnormalities in O(2) diffusion, ventilation-perfusion inequality, or hemodynamic function, we studied these animals via the multiple inert gas elimination technique at rest and during exercise at a constant workload equivalent to 50% or 80% of peak O(2) uptake while breathing 21% and 14% O(2) in balanced order. From rest to exercise after splenectomy, minute ventilation was significantly elevated with respect to O(2) uptake compared with exercise before splenectomy; cardiac output, O(2) delivery, and mean pulmonary and systemic arterial blood pressures were 10-20% lower, while O(2) extraction was elevated with respect to O(2) uptake. Ventilation-perfusion inequality was unchanged, but O(2) diffusing capacities of lung (DL(O2)) and peripheral tissue during exercise were lower with respect to cardiac output postsplenectomy by 32% and 25%, respectively. The relationship between DL(O2) and DL(CO) was unchanged by splenectomy. We conclude that the canine spleen regulates both convective and diffusive O(2) transport during exercise to increase maximal O(2) uptake.

Measurement of cardiac output by open-circuit acetylene uptake: a computer model to quantify error caused by ventilation–perfusion inequality

The ability to assess cardiac output noninvasively has been the focus of interest for many researchers. While the open-circuit acetylene (C2H2) method seems promising, it is prone to error due to ventilation–perfusion inequality. Measurements during exercise, at high altitude or in patients with chronic obstructive pulmonary disease (COPD) could be unreliable and further validation studies under these circumstances may be needed. We used a computer model based on formulae derived from the multiple inert gas elimination technique to quantify error in measurements resulting from inequality at rest, during exercise or at high altitude. Moreover, potential errors encountered in patients with COPD were quantified. In healthy subjects, inequality related measurement error seems negligible, under both normoxic and hypoxic conditions and especially during exercise. In COPD, errors up to 20% at rest and up to 15% during exercise are expected. It is therefore concluded from our model that the open-circuit C2H2 uptake method is expected to be accurate in normal subjects. Its validity in COPD needs further study.