Functional capacities of the lungs and thorax in beagles taken to high altitude as adults for 33 mo or in beagles raised from puppies at high altitude were compared with functional capacities in corresponding sets of beagles kept simultaneously at sea level. Comparisons were made after reacclimatization to sea level. Lung volumes, airway pressures, esophageal pressures, CO diffusing capacities (DLCO), pulmonary blood flow, and lung tissue volume (Vt) were measured by a rebreathing technique at inspired volumes ranging from 15 to 90 ml/kg. In beagles raised from puppies we measured anatomical distribution of intrathoracic air and tissue using X-ray computed tomography at transpulmonary pressures of 20 cm H2O. Lung and thoracic distensibility, DLCO, and Vt were not different between beagles that had been kept at high altitude for 33 mo as adults and control subjects kept simultaneously at sea level. Lung distensibility, DLCO, and Vt were significantly greater in beagles raised at high altitude than control subjects raised simultaneously at sea level. Thoracic distensibility was not increased in beagles raised at high altitude; the larger lung volume was accommodated by a lower diaphragm, not a larger rib cage.

Our purpose was to reexamine the relationship of the fall in cardiac output and blood pressure which occurs during positive end-expiratory pressure (PEEP) to changes in transmural right atrial and left atrial filling pressures. Closed-chest dogs, half with pulmonary edema, were studied during spontaneous breathing and inspiratory positive-pressure breathing (IPPB) with 0-15 cmH2O PEEP. Mean esophageal pressure accurately reflected changes in pericardial pressure and was used to estimate extracardiac pressure. We found that cardiac output fell approximately 50% and blood pressure fell 20% during 15 cmH2OPEEP in spite of well maintained transmural right atrial and left atrial (or pulmonary artery wedge) pressures suggesting a primary or reflex depression of atrial or ventricular function.

Loss of a major portion of lung tissue has been associated with impaired exercise capacity, but the underlying mechanisms are not well defined. We studied the alterations in gas exchange during exercise before and after left pneumonectomy in three conditioned foxhounds. After pneumonectomy, minute ventilation and O2 consumption at comparable submaximal work loads were unchanged but arterial PCO2 at any work load was higher, implying that ventilatory response to CO2 was impaired. Arterial hypoxemia and an elevated alveolar-arterial O2 tension difference (AaDO2) developed during heavy exercise. Using the multiple inert gas elimination technique, we determined the distributions of ventilation-perfusion (VA/Q) ratios postpneumonectomy. Significant increase in VA/Q inequality developed during exercise while the foxhounds were breathing room air, accounting for an average of 42% of the total increase in AaDO2 while diffusion limitation accounted for 58%. While the animals were breathing hypoxic gas mixture, diffusion limitation accounted for an average of 88% of the total increase AaDO2. Cardiac output and O2 delivery were reduced at a given O2 consumption after pneumonectomy. After pneumonectomy, the animals reached O2 consumptions close to the maximum expected for normal dogs. Compensation for the impairment in O2 delivery post-pneumonectomy occurred mainly by an increase in hemoglobin concentration. Training probably played an important role in returning exercise capacity toward prepneumonectomy levels. We conclude that significant abnormalities in gas exchange develop during exercise after loss of 42% of lung tissue, but the animals demonstrate a remarkable ability to compensate for these changes.

In dogs, inflating the lungs to pressures of 9 cm H2O or less reflexly increases heart rate, whereas inflating the lungs to pressures of 10-30 cm H2O reflexly decreases heart rate. The afferent fibers responsible for the cardioacceleration travel in the vagus nerves and are believed to be pulmonary stretch receptors, whereas the afferent responsible for the deceleration also travel in the vagus nerves, but are believed to be lung C-fibers. To identify the afferents responsible for these effects, we recorded the impulse activity of vagal afferents with endings in the left lung, while we slowly inflated that lung to 30-45 cm H2O. We found that 12 slowly adapting receptors fired at significantly lower inflation pressures than did 10 rapidly adapting receptors (5.8 +/- 1.5 vs. 13.5 +/- 2.2 cm H2O, respectively). We also found that 13 pulmonary C-fibers fired at significantly lower inflation pressures than did 10 bronchial C-fibers (16.4 +/- 1.8 vs 26.5 %/- 2.9 cm H2O, respectively). We conclude that slowly adapting receptors are likely to be responsible for the cardioacceleration evoked by low levels of inflation, and that both pulmonary and bronchial C-fibers are likely to be responsible for the cardiodeceleration evoked by high levels of inflation.

Although the left lung constitutes 42% of the total by weight and volume in dogs, carbon monoxide diffusing capacity (DL) after left pneumonectomy in adults falls less than 30% at rest, indicating a significant increase of DL in the remaining lung. DL normally increases during exercise, presumably by recruitment of alveolar capillaries and surface area as lung volume (Vs) and pulmonary blood flow (Qc) increase. We asked whether the increase of DL in the remaining lung after pneumonectomy in adult dogs could be explained by this kind of passive recruitment by the increased volume and Qc in the remaining lung. We measured the relationship between DL and Qc with a rebreathing technique at increasing treadmill loads in adult foxhounds, before and 6 mo after left pneumonectomy, and the relationship between DL and Vs by the same technique under anesthesia as Vs was expanded. DL was reduced by 29.1% at rest and 26.5% with heavy exercise after left pneumonectomy, indicating either recruitment or new growth in the right lung. With the assumption that the right lung normally receives 58% of the Qc and contains 58% of the DL, DL of the right lung increased with Qc in accordance with the following relationships before and after left pneumonectomy: right lung DL (before pneumonectomy) = 6.44 + 2.40(Qc) (r = 0.963) and right lung DL (after pneumonectomy) = 7.51 + 1.75(Qc) (r = 0.958). Only approximately 7% of the increase in DL from rest to peak exercise could be attributed to the increase in Vs during exercise before pneumonectomy and approximately 15% after pneumonectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Single-breath diffusing capacity of the lung for carbon monoxide (DLCO) increases as lung volume increases above functional residual capacity (FRC). However, the physiological mechanism responsible for this increase remains controversial. This volume dependence of diffusing capacity could reflect changing regional distribution of inspired air as lung volume increases rather than a change in capillary blood volume or surface area for gas exchange. We measured DLCO during breath holding and during rebreathing with a technique employed to mix respired gases throughout the lung thereby minimizing regional distribution differences. Measurements were made 1,500 ml above FRC and near total lung capacity (TLC). Breath holding DLCO was 18% higher near TLC than at 1,500 ml above FRC (P less than 0.05). Rebreathing DLCO was 16% higher near TCL than at 1,500 ml above FRC (P less than 0.01). Equality of results by the two techniques indicates that changes in DLCO with lung volume are not a consequence of the changing distribution of inspired air. Our results are compatible with the hypothesis that effective surface area of the lung increases as lung volume expands.

Pulmonary arterial pressure is higher during exercise after pneumonectomy than before. Several factors may contribute to the elevation, e.g., loss of vascular bed, overinflation of the remaining lung, and active pulmonary vasoconstriction. We measured hemodynamic changes during graded exercise in conditioned foxhounds and compared pulmonary pressure-flow relationships before and after left pneumonectomy. Pulmonary arterial pressure-flow relationship in the remaining lung is not altered by pneumonectomy, suggesting that the increase in pulmonary vascular resistance post-pneumonectomy is largely the passive consequence of increased pulmonary blood flow to the remaining lung. The potential for chronic hyperinflation of the remaining lung to increase pulmonary resistance after pneumonectomy may have been counterbalanced by a concomitant reduction in lung elastic recoil. Unexpectedly, both mean systemic blood pressure and hematocrit were higher with respect to cardiac output after pneumonectomy. Cardiac output and stroke volume at any given work load were lower after pneumonectomy than before, and heart rate response was unaltered. This pattern of responses suggests that increases in left and right ventricular afterload may have contributed to the reduction in cardiac output.

In normal subjects during 15-min positive-pressure ventilation with 10 cmH2O end-expiratory pressure (PEEP), cardiac output fell 19% due to a fall in stroke volume. Transmural mean right atrial pressure rose 3.1 cmH2O and right ventricular end-diastolic diameter increased 15%. Simultaneously, left ventricular end-diastolic diameter decreased 21%, ejection time increased 11%, and velocity of circumferential fiber shortening fell 30%. Thus, right ventricular filling increased and left ventricular filling decreased. The function of the right ventricle was impaired and the function of the left ventricle may have been impaired. Cardiac output gradually increased due to a 7% increase in heart rate as PEEP was continued for 1 h and transmural mean right atrial pressure also increased further by 2.4 cmH2O. Compensation for the reduced stroke volume occurred as filling pressures and heart rate rose, but ventricular function remained impaired for the entire duration of PEEP. On resuming spontaneous breathing, cardiac output and ventricular function returned to base-line levels. We conclude that the reduced cardiac output during PEEP is not due to a direct mechanical reduction in right ventricular filling.