To test the hypothesis that activity of respiratory muscles determines regional growth of lung parenchyma, we studied the effects of unilateral diaphragmatic paralysis on contralateral/ipsilateral lung growth in cats and piglets. Five 10- to 12-wk-old cats and five 8-wk-old piglets underwent unilateral diaphragmatic paralysis by thoracic and cervical phrenectomy, respectively. Five to seven weeks after surgery, when the cats were killed for studies of lung growth, gain in body weight was the same as in five sham-operated controls. At this time, mean pleural pressure ipsilateral to the paralyzed hemidiaphragm was the same as contralateral mean pleural pressure during tidal breathing, and values did not differ from controls. However overall functional residual capacity was lower in the phrenectomized cats (35 +/- 4 ml) than in the controls (55 +/- 11 ml, P less than 0.01). Growth of contralateral lungs relative to ipsilateral lungs was greater in the phrenectomized cats than in the controls, as shown by ratios of contralateral/ipsilateral wet lung weight (1.44 vs. 1.34, P less than 0.01), maximum inflation volume (1.53 vs. 1.33, P less than 0.05), and total protein content (1.45 vs. 1.26, P less than 0.05). Ratios of total protein to DNA and RNA to DNA were unchanged. One week after surgery in the piglets, the ratio of contralateral/ipsilateral wet lung weight was increased (1.61 vs. 1.29, P less than 0.01) and total weight of both lungs was reduced. We conclude that regional growth of lung parenchyma by cell proliferation depends in part on regional distribution of respiratory muscle activity.

ABSTRACT. To test the hypothesis that regional growth of lung parenchyma depends on regional distending pressure, left cervical phrenectomy was done in ten 2-monthold piglets. The unilateral diaphragmatic paralysis reduced mean transpulmonary pressure in the left hemithorax from 5.5 f 1.0 (% f SD) to 2.5 +. Several determinants of postnatal lung growth have been suggested by experiments with compensatory lung growth after pneumonectomy or lung collapse (1). In particular, the compensatory response is inhibited by plombage of the thoracic cavity (2, 3), which indicates a determinant involving lung and chest wall mechanics. However, the possibility of a mechanical determinant is difficult to pursue further within the model of compensatory lung growth, which is complicated by loss of functioning lung tissue, ventilatory embarrassment and, in some cases, disturbance in body growth. Recently, Mansell et al. (4) altered regional, postnatal lung growth by producing unilateral diaphragmatic paralysis in cats and pigs. Because there was no loss of functioning lung tissue and no disturbance in body growth, unilateral diaphragmatic paralysis appeared to be a good model for studying mechanical factors affecting postnatal lung growth.Herein we examine pulmonary distending pressure as a possible mechanical determinant of lung growth after unilateral diaphragmatic paralysis. Bilateral pleural balloons are used in the piglet, where unilateral phrenectomy can be done reliably by the cervical approach and where a relatively stiff mediastinum is expected to promote pressure differences between the two hemithoraces. In addition, unique data are presented for acute changes in bilateral transpulmonary pressure after unilateral cervical phrenectomy. METHODS Animals and surgical procedures. Twenty 8-wk-old femaleYorkshire piglets, purchased from T. Moms, Inc., Reisterstown, MD, were anaesthetized using nitrous oxide and maintained with halothane. The piglets were restrained in the supine position with the left forelimb abducted to orient the brachial plexus at right angles to the phrenic nerve. A midline incision was made extending 6 cm below the hyoid cartilage, and a flap was extended laterally until the carotid sheath with the vagus nerve was located. The phrenic nerve was traced caudad until it coursed dorsal to the subclavian artery. The nerve was stimulated electrically and diaphragmatic contraction was verified visually. A I-cm segment of the nerve was then excised in 10 experimental animals, whereas in the 10 controls neither electrical stimulation nor excision was performed. Experimental and control procedures were alternated.In five of the experimental piglets and in their five controls, bilateral pleural pressures were measured before and 30 min after the surgical procedure. These 10 piglets were killed 48 h after the surgical procedure and their lungs were removed for measurements of wet weight, total protein, DNA, and RNA. In the other five experimental animals, and in their controls, bilateral pleural pressures were measu...