Altered diaphragm function modifies neonatal lung growth: Biologic morphometric assessment

Abstract

Thoracic volume relationships supported by the diaphragm are important mechanical components of neonatal lung growth. Alterations modify regional lung growth. We used stereologic morphometry to study effects of altered diaphragm function on alveolar growth in neonatal pigs. Nine piglets (1 mo) were divided into three groups: unilateral phrenectomy, noncompliant patch replacement of diaphragm, and sham. Seven days later lungs were fixed in situ with 2.5% glutaraldehyde by airway installation at 20 cm H 2O. Five 1-mm cubes were cut from lung corresponding to epex/RUQ(A), base/RLQ(B), apex/LUQ(C), and base/LLQ(D) and prepared for light microscopy (n = 25/quad/animal). Stereologic morphometry involved point counting for air volume density and point intersect to determine the surface area density of the alveolar spaces. Results were analyzed for variance and by Tukey range testing. Variance of air volume % between groups-quadrants B, C, D had decreased air volume % in phrenectomy group compared with patch and sham group ( P < .05). Variance of air volume % within groups, for phrenectomy group A (81.5%), is different from all others (B = 70.6%, C = 75.5%, D = 66.7%); C is different from D ( P < .05). For patch and sham group, D (P = 74.8%, S = 80.7%) is different from A (P = 84.1%, S = 86.6%) and C (P = 86.2%, S = 84.4%). Variance of surface area density between groups—quadrant D had increased surface area density % in phrenectomy group compared to sham group ( P < .05). Variance of surface area density % within groups, for phrenectomy group, A (37.9 mm-1) is different from D (55.7 mm-1). In conclusion: (1) Phrenectomy causes loss of thoracic volume relationships, decreasing alveolar air space volume and increasing surface area density/unit volume in quadrants nearest to paralyzed diaphragm compared to sham. (2) Normalization of thoracic volume relationships by noncompliant patch prevents loss of air volume in quadrants nearest affected diaphragm despite a relative increase in nongas-exchange respiratory tissue (surface area density). (3) Thoracic volume relationships are important in establishing alveolar air space volume in the neonatal period.