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

Abstract

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.

Quantitative morphology of compensatory lung growth

“…After pneumonectomy, perfusion to the remaining lung doubles immediately; parenchymal growth following stabilisation of perfusion is associated with proportional increases in HRCT-derived tissue and blood volumes; physiological measurements of membrane diffusing capacity and capillary blood volume also increase proportionally [22,69,71]. In adult dogs, the post-pneumonectomy compensatory increase in HRCTderived lobar tissue volume is markedly heterogeneous ( fig.…”

“…Post-pneumonectomy compensation is slow and incomplete in the adult lung [20,21] but rapid and vigorous in the growing lung [22], an indication of the additive effects of developmental and post-pneumonectomy stimuli. In both young and adult dogs undergoing right pneumonectomy, alveolar septa in the remaining lung initially become thickened owing to a disproportionate increase in interstitial cells and matrix by nearly 3.6-fold, while epithelial and endothelial cells increase about two-fold compared with the control lung.…”

“…In contrast, the extra-acinar conducting airways do not branch or proliferate post-pneumonectomy but adapt by elongation [55,56] and dilatation [57][58][59], which is evident on morphological analysis. The long-term compensatory increases in airway volume and cross-sectional area lag behind the increase in parenchyma volume, leading to persistently elevated airways resistance and work of breathing [60] even as alveolar gas exchange normalises [22] .1 yr after pneumonectomy. The effects of dissociated or dysanaptic growth rates between conducting and gas exchange structure are more pronounced in dogs undergoing pneumonectomy as puppies than as adults, and imposes a mechanical limit on the function of the remaining lung that curtails the effectiveness of alveolar growth.…”

Avaliação hemogasométrica em cães submetidos à pneumonectomia esquerda

“…Entretanto, verificou-se que, nos momentos seguintes, a PaO 2 já retornava a valores do intervalo fisiológico para, no T36d, não mais apresentar diferenças significativas em relação ao T0. Estes resultados corroboram com os obtidos por Carlin et al (1991), Hsia et al (1994) e Takeda et al (1999) no pós-operatório mediato. Esta hipoxemia momentânea verificada uma hora após a extubação pode estar relacionada a diferentes fatores.…”

“…Estes resultados vêm ao encontro daqueles descritos por Carlin et al (1991), Hsia et al (1994) e Takeda et al (1999) no pós-operatório mediato, como já ressaltado no segundo parágrafo da discussão.…”