Effect of increased gas density on pulmonary gas exchange in man.

Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.     

Mechanisms of improvement in pulmonary gas exchange during isovolemic hemodilution.

Severe anemia is associated with remarkable stability of pulmonary gas exchange (S. Deem, M. K. Alberts, M. J. Bishop, A. Bidani, and E. R. Swenson. J. Appl. Physiol. 83: 240-246, 1997), although the factors that contribute to this stability have not been studied in detail. In the present study, 10 Flemish Giant rabbits were anesthetized, paralyzed, and mechanically ventilated at a fixed minute ventilation. Serial hemodilution was performed in five rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; five rabbits were followed over a comparable time. Ventilation-perfusion (VA/Q) relationships were studied by using the multiple inert-gas-elimination technique, and pulmonary blood flow distribution was assessed by using fluorescent microspheres. Expired nitric oxide (NO) was measured by chemiluminescence. Hemodilution resulted in a linear fall in hematocrit over time, from 30 +/- 1.6 to 11 +/- 1%. Anemia was associated with an increase in arterial PO(2) in comparison with controls (P < 0.01 between groups). The improvement in O(2) exchange was associated with reduced VA/Q heterogeneity, a reduction in the fractal dimension of pulmonary blood flow (P = 0.04), and a relative increase in the spatial correlation of pulmonary blood flow (P = 0. 04). Expired NO increased with anemia, whereas it remained stable in control animals (P < 0.0001 between groups). Anemia results in improved gas exchange in the normal lung as a result of an improvement in overall VA/Q matching. In turn, this may be a result of favorable changes in pulmonary blood flow distribution, as assessed by the fractal dimension and spatial correlation of blood flow and as a result of increased NO availability.     

Effect of acute increases in pulmonary vascular pressures on exercise pulmonary gas exchange.

The purpose of this study was to determine the effect of acute increases in pulmonary vascular pressures, caused by the application of lower-body positive pressure (LBPP), on exercise alveolar-to-arterial PO2 difference (A-aDO2), anatomical intrapulmonary (IP) shunt recruitment, and ventilation. Eight healthy men performed graded upright cycling to 90% maximal oxygen uptake under normal conditions and with 52 Torr (1 psi) of LBPP. Pulmonary arterial (PAP) and pulmonary artery wedge pressures (PAWP) were measured with a Swan-Ganz catheter. Arterial blood samples were obtained from a radial artery catheter, cardiac output was calculated by the direct Fick method, and anatomical IP shunt was determined by administering agitated saline during continuous two-dimensional echocardiography. LBPP increased both PAP and PAWP while upright at rest, and at all points during exercise (mean increase in PAP and PAWP 3.7 and 4.0 mmHg, respectively, P<0.05). There were no differences in exercise oxygen uptake or cardiac output between control and LBPP. Despite the increased PAP and PAWP with LBPP, A-aDO2 was not affected. In the upright resting position, there was no evidence of shunt in the control condition, whereas LBPP caused shunt in one subject. At the lowest exercise workload (75 W), shunt occurred in three subjects during control and in four subjects with LBPP. LBPP did not affect IP shunt recruitment during subsequent higher workloads. Minute ventilation and arterial PcO2 were not consistently affected by LBPP. Therefore, small acute increases in pulmonary vascular pressures do not widen exercise A-aDO2 or consistently affect IP shunt recruitment or ventilation.     

Effects of hypoxic pulmonary vasoconstriction on pulmonary gas exchange

Brimioulle, Serge, Philippe Lejeune, and Robert Naeije.Effects of hypoxic pulmonary vasoconstriction on pulmonary gasexchange. J. Appl. Physiol. 81(4):1535-1543, 1996.Several reports have suggested that hypoxicpulmonary vasoconstriction (HPV) might result in deterioration ofpulmonary gas exchange in severe hypoxia. We therefore investigated theeffects of HPV on gas exchange in normal and diseased lungs. Weincorporated a biphasic HPV stimulus-response curve observed in intactdogs (S. Brimioulle, P. Lejeune, J. L. Vachièry, M. Delcroix, R. Hallemans, and R. Naeije, J. Appl.Physiol. 77: 476-480, 1994) into a 50-compartment lung model (J. B. West, Respir.Physiol. 7: 88-110, 1969) to control the amount ofblood flow directed to each lung compartment according to the localhypoxic stimulus. The resulting model accurately reproduced the bloodgas modifications caused by HPV changes in dogs with acute lung injury.In single lung units, HPV had a moderate protective effect on alveolaroxygenation, which was maximal at near-normal alveolarPO₂ (75-80 Torr), mixed venousPO₂ (35 Torr), andPO₂ at which hemoglobin is 50%saturated (24 Torr). In simulated diseased lungs associated with40-60 Torr arterial PO₂,however, HPV increased arterial PO₂ by 15-20 Torr. We conclude that HPV can improve arterialoxygenation substantially in respiratory failure.

     

Intravital microscopy of the murine pulmonary microcirculation.

Intravital microscopy (IVM) is considered as the gold standard for in vivo investigations of dynamic microvascular regulation. The availability of transgenic and knockout animals has propelled the development of murine IVM models for various organs, but technical approaches to the pulmonary microcirculation are still scarce. In anesthetized and ventilated BALB/c mice, we established a microscopic access to the surface of the right upper lung lobe by surgical excision of a window of 7- to 10-mm diameter from the right thoracic wall. The window was covered by a transparent polyvinylidene membrane and sealed with alpha-cyanoacrylate. Removal of intrathoracic air via a trans-diaphragmal intrapleural catheter coupled the lung surface to the window membrane. IVM preparations were hemodynamically stable for at least 120 min, with mean arterial blood pressure above 70 mmHg, and mean arterial Po(2) and arterial Pco(2) in the range of 90-100 Torr and 30-40 Torr, respectively. Imaged lungs did not show any signs of acute lung injury or edema. Following infusion of FITC dextran, subpleural pulmonary arterioles and venules of up to 50-microm diameter and alveolar capillary networks could be visualized during successive expiratory plateau phases over a period of at least 2 h. Vasoconstrictive responses to hypoxia (11% O(2)) or infusion of the thromboxane analog U-46619 were prominent in medium-sized arterioles (30- to 50-microm diameter), minor in small arterioles <30 microm, and absent in venules. The presented IVM model may constitute a powerful new tool for investigations of pulmonary microvascular responses in mice.     

Understanding pulmonary gas exchange: ventilation-perfusion relationships

This essay looks at the historical significance of four APS classic papers that are freely available online: Fenn WO, Rahn H, and OTIS AB. A theoretical study of the composition of the alveolar air at altitude. Am J Physiol 146: 637-653. 1946 (http://ajplegacy.physiology.org/cgi/reprint/146/5/637). Rahn H. A concept of mean alveolar air and the ventilation-bloodflow relationships during pulmonary gas exchange. Am J Physiol 158: 21-30, 1949 (http://ajplegacy.physiology.org/cgi/reprint/158/1/21)). Riley RL. And Cournand A. "Ideal" Alveolar air and the analysis of ventilation-perfusion relationships in the lungs. J Appl Physiol 1: 825-847. 1949 (http://jap.physiology.org/cgi/reprint/1/12/825). Riley RL. And Cournand A. Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of lungs: theory. J Appl Physiol 4: 77-101. 1951 (http://jap.physiology.org/cgi/reprint/4/2/77).     

Effects of crocetin on pulmonary gas exchange in foxhounds during hypoxic exercise.

The carotenoid compound crocetin has been hypothesized to enhance the diffusion of O(2) through plasma, and observations in the rat and rabbit have revealed improvement in arterial PO(2) when crocetin is given. To determine whether crocetin enhances diffusion of O(2) between alveolar gas and the red blood cell in the pulmonary capillary in vivo, five foxhounds, two previously subjected to sham and three to actual lobectomy or pneumonectomy, were studied while breathing 14% O(2) at rest and during moderate and heavy exercise before and within 10 min after injection of a single dose of crocetin as the trans isomer of sodium crocetinate (TSC) at 100 microg/kg iv. This dose is equivalent to that used in previous studies and would yield an initial plasma concentration of 0.7-1.0 microg/ml. Ventilation-perfusion inequality and pulmonary diffusion limitation were assessed by the multiple inert gas elimination technique in concert with conventional measurements of arterial and mixed venous O(2) and CO(2). TSC had no effect on ventilation, cardiac output, O(2) consumption, arterial PO(2)/saturation, or pulmonary O(2) diffusing capacity. There were minor reductions in ventilation-perfusion mismatching (logarithm of the standard deviation of perfusion fell from 0.48 to 0.43, P = 0.001) and in CO(2) output and respiratory exchange ratio (P = 0.05), which may have been due to TSC or to persisting effects of the first exercise bout. Spectrophotometry revealed that TSC disappeared from plasma with a half time of approximately 10 min. We conclude that, in this model of extensive pulmonary O(2) diffusion limitation, TSC as given has no effect on O(2) exchange or transport. Whether the original hypothesis is invalid, the dose of TSC was too low, or plasma diffusion of O(2) is not rate limiting without TSC cannot be discerned from the present study.     

Long-term enhancement of pulmonary gas exchange after high-altitude residence during maturation.

In a previous study, our laboratory showed that young dogs born at sea level (SL) and raised from 2.5 mo of age to beyond somatic maturity at a high altitude (HA) of 3,100 m show enhanced resting lung function (Johnson RL Jr, Cassidy SS, Grover RF, Schutte JE, and Epstein RH. J Appl Physiol 59: 1773-1782, 1985). To examine whether HA-induced adaptation improves pulmonary gas exchange during exercise and whether adaptation is reversible when animals return to SL before somatic maturity, we raised 2.5-mo-old foxhounds at HA (3,800 m) for 5 mo (to age 7.5 mo) before returning them to SL. Lung function was measured under anesthesia 1 mo and 2 yr after return to SL and during exercise approximately 1 yr after return. In animals exposed to HA relative to simultaneous litter-matched SL controls, resting circulating blood and erythrocyte volumes, lung volumes, septal volume estimated by a rebreathing technique, and lung tissue volume estimated by high-resolution computed tomography scan were persistently higher. Lung diffusing capacity, membrane diffusing capacity, and pulmonary capillary blood volume estimated at a given cardiac output were significantly higher in animals exposed to HA, whereas maximal oxygen uptake and hematocrit were similar between groups. We conclude that relatively short exposure to HA during somatic maturation improves long-term lung function into adulthood.     

Glimpses into measurements of the microcirculation in skin

There are instances when chronic disease states manifest as microvascular disturbances of the skin. Objective assessment of these disturbances would permit a better understanding of the causative factors and, in certain circumstances, influence decisions of clinical management. Recent advances in technology that permit such assessment non-invasively are evaluated in this review.     

Initiation of pulmonary gas exchange by fetal sheep in utero

The role of umbilical cord occlusion in the initiation of breathing at birth was investigated using unanesthetized fetal sheep that were provided with access to a tracheal supply of hyperoxic air. Near-term fetuses were studied in utero to eliminate extraneous sensory stimuli. Gasping movements began 1.4 +/- 0.1 min after cord occlusion. Breathing was irregular for several minutes before continuous breathing (greater than or equal to 40 min-1) began 6 +/- 1 min after cord occlusion (n = 10). Arterial PO2 rose significantly from 18 +/- 2 mmHg before occlusion and was 115 +/- 15 mmHg immediately before cord release at 15 or 30 min. Breathing continued even during high-voltage electrocortical activity. Cord release caused the breathing rate to decrease from 77 +/- 13 min-1 during the last 5 min of cord occlusion to 5 +/- 3 min-1 10 min after cord release (P less than 0.002; n = 7). Results indicate the change from placental to lung gas exchange can occur in the absence of sensory and thermal changes normally present at birth and that the transition is reversible.