Recruitment of lung diffusing capacity with exercise before and after pneumonectomy in dogs

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)     

Effect of cyclooxygenase inhibition on ethchlorvynol-induced acute lung injury in dogs

In anesthetized dogs ethchlorvynol (ECV, 9 mg/kg) was selectively administered into the right pulmonary circulation to produce unilateral acute lung injury (ALI) characterized by nonhydrostatic pulmonary edema and systemic hypoxemia. To investigate the hypothesis that products of cyclooxygenase activity are mediators of the arterial hypoxemia, but not the edema formation in this injury, animals were pretreated with one of two chemically dissimilar cyclooxygenase inhibitors, indomethacin (5 mg/kg), or ibuprofen (12.5 mg/kg), or vehicle (0.1 M sodium carbonate) prior to the administration of ECV. Pretreatment with either inhibitor prevented the ECV-induced systemic hypoxemia observed in animals pretreated with vehicle (P less than 0.01). Despite this protection of systemic oxygenation, there was no redistribution of blood flow to the uninjured lung following unilateral ECV administration. Cyclooxygenase inhibition prior to ALI did not attenuate the accumulation of lung water. In the ibuprofen group, left atrial pressure increased significantly following ECV administration. We conclude that a product(s) of cyclooxygenase-mediated arachidonic acid metabolism is responsible for the altered vascular reactivity and consequent systemic hypoxemia in this model, but that the edema formation following ECV is not related to cyclooxygenase activity. In addition, ibuprofen, administered prior to the induction of ALI, exhibits properties not shared by indomethacin but is not different in its capacity to attenuate hypoxemia or in its failure to limit edema formation.     

Respiratory muscle blood flow in exercising dogs after pneumonectomy.

In three foxhounds after left pneumonectomy, the relationships of ventilatory work and respiratory muscle (RM) blood flow to ventilation (VE) during steady-state exercise were examined. VE was measured using a specially constructed respiratory mask and a pneumotach; work of breathing was measured by the esophageal balloon technique. Blood flow to RM was measured by the radionuclide-labeled microsphere technique. Lung compliance after pneumonectomy was 55% of that before pneumonectomy; compliance of the thorax was unchanged. O2 uptake (VO2) of RM comprised only 5% of total body VO2 at exercise. At rest, inspiratory muscles received 62% and expiratory muscles 38% of the total O2 delivered to the RM (QO2RM). During exercise, inspiratory muscles received 59% and expiratory muscles 41% of total QO2RM. Blood flow per gram of muscle to the costal diaphragm was significantly higher than that to the crural diaphragm. The diaphragm, parasternals, and posterior cricoarytenoids were the most important inspiratory muscles, and internal intercostals and external obliques were the most important expiratory muscles for exercise. Up to a VE of 120 l/min through one lung, QO2RM constituted only a small fraction of total body VO2 during exercise and maximal vasodilation in the diaphragm was never approached.     

Effect of superior vena caval hypertension on alloxan-induced lung injury in dogs

To investigate how fast and to what extent superior vena caval hypertension (SVCH) increases lung water in acute increased-permeability state, we studied the time course of lung water accumulation for 3 h in anesthetized dogs under different treatments: 1) controls without intervention (5 dogs), 2) SVCH alone (5 dogs), 3) mild lung microvascular injury induced by low-dose alloxan (75 mg/kg) alone (5 dogs), and 4) SVCH coupled with low-dose alloxan (5 dogs). Neither low-dose alloxan alone nor SVCH alone [superior vena caval pressure (Psvc) = 11.0 +/- 3.1 (SD) mmHg] increased lung water significantly. The SVCH coupled with low-dose alloxan (Psvc = 11.3 +/- 2.7 mmHg) doubled extravascular lung thermal volume measured by the thermal-dye dilution technique within 1 h (5.3 +/- 0.9 ml/kg at base line and 10.9 +/- 4.7 ml/kg at 1 h), then remained unchanged (12.5 +/- 5.7 ml/kg at 3 h). This increase in lung water was confirmed by gravimetric method (5.69 +/- 1.71 g/g blood-free dry wt). We conclude that SVCH is one of the factors that may promote lung water accumulation in increased-permeability state.     

Computational analysis of lung deformation after murine pneumonectomy

In many mammalian species, the removal of one lung (pneumonectomy) is associated with the compensatory growth of the remaining lung. To investigate the hypothesis that parenchymal deformation may trigger lung regeneration, we used microCT scanning to create 3D finite element geometric models of the murine lung pre- and post-pneumonectomy (24 h). The structural correspondence between models was established using anatomic landmarks and an iterative computational algorithm. When compared with the pre-pneumonectomy lung, the post-pneumonectomy models demonstrated significant translation and rotation of the cardiac lobe into the post-pneumonectomy pleural space. 2D maps of lung deformation demonstrated significant heterogeneity; the areas of greatest deformation were present in the subpleural regions of the lobe. Consistent with the previously identified growth patterns, subpleural regions of enhanced deformation are compatible with a mechanical signal – likely involving parenchymal stretch – triggering lung growth.     

Effect of heart weight on distribution of lung surface pressures in vertical dogs

In head-up dogs the vertical gradient of transpulmonary pressure (VGTP) disappears after pneumothorax develops. Our laboratory recently confirmed that the heart moves downward and posteriorly with pneumothorax. To study the extent to which the heart is supported by the lungs, we used a linear elasticity model and finite-element analysis. The lung and heart were assumed to be symmetric along a vertical axis. Reported values of the elastic properties of lung and heart were assigned. The model was generated first without the heart, using the lung alone. The heart was then added to the model. Finally, heart weight was doubled. Adding the heart caused the VGTP to increase; doubling the heart weight further increased the VGTP. These increases were more pronounced at higher lung volumes. Lung inflation was accompanied by an upward displacement of the heart. Inclusion of the heart caused increased inhomogeneities in regional volume distribution. The effect of heart weight may in part explain why the VGTP in the head-up dog is greater than that predicted by lung density.     

Action of intercostal muscles on the lung in dogs

The action on the lung of interosseous intercostal muscles located in the third and the seventh interspaces was studied in 15 anesthetized-curarized supine dogs. Changes in pleural pressure, airflow rate, and lung volume produced by maximal stimulation of both intercostal muscle layers were measured at and above functional residual capacity (FRC). In five animals measurements were also obtained during isolated stimulation of the internal layer. At FRC, intercostal stimulation in the upper interspaces had invariably an inspiratory effect on the lung but no effect was detectable in the lower interspaces. Qualitatively similar results were obtained during isolated stimulation of the internal layer. Increasing lung volume reduced the inspiratory action of the upper intercostals and conferred an expiratory action to the lower intercostals. These results indicate the following: 1) when contracting in a single interspace, the external and internal intercostals have a qualitatively similar action on the lung; and 2) this action, however, depends critically on their location along the cephalocaudal axis of the rib cage: in the upper portion of the rib cage, both muscle layers have an inspiratory effect at and above FRC; in the lower portion of the rib cage, they have no respiratory action at FRC and act in the expiratory direction at higher lung volumes.     

Compensatory alveolar growth normalizes gas-exchange function in immature dogs after pneumonectomy.

To determine the extent and sources of adaptive response in gas-exchange to major lung resection during somatic maturation, immature male foxhounds underwent right pneumonectomy (R-Pnx, n = 5) or right thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. One year after surgery, exercise capacity and pulmonary gas-exchange were determined during treadmill exercise. Lung diffusing capacity (DL) and cardiac output were measured by a rebreathing technique. In animals after R-Pnx, maximal O2 uptake, lung volume, arterial blood gases, and DL during exercise were completely normal. Postmortem morphometric analysis 18 mo after R-Pnx (n = 3) showed a vigorous compensatory increase in alveolar septal tissue volume involving all cellular compartments of the septum compared with the control lung; as a result, alveolar-capillary surface areas and DL estimated by morphometry were restored to normal. In both groups, estimates of DL by the morphometric method agreed closely with estimates obtained by the physiological method during peak exercise. These data show that extensive lung resection in immature dogs stimulates a vigorous compensatory growth of alveolar tissue in excess of maturational lung growth, resulting in complete normalization of aerobic capacity and gas-exchange function at maturity.