Ultrastructural appearances of pulmonary capillaries at high transmural pressures

Abstract

Electronmicroscopic appearances of pulmonary capillaries were studied in rabbit lungs perfused in situ when the capillary transmural pressure (Ptm) was systematically raised from 12.5 to 72.5 +/- 2.5 cmH2O. The animals were anesthetized and exsanguinated, and after the chest was opened, the pulmonary artery and left atrium were cannulated and attached to reservoirs. The lungs were perfused with autologous blood for 1 min, and this was followed by saline-dextran and then buffered glutaraldehyde to fix the lungs for electron microscopy. Normal appearances were seen at 12.5 cmH2O Ptm. At 52.5 and 72.5 cmH2O Ptm, striking discontinuities of the capillary endothelium and alveolar epithelium were seen. A few disruptions were seen at 32.5 cmH2O Ptm (mostly in one animal), but the number of breaks per millimeter cell lining increased markedly up to 72.5 cmH20 Ptm, where the mean frequency was 27.8 +/- 8.6 and 13.6 +/- 1.4 (SE) breaks/mm for endothelium and epithelium, respectively. In some instances, all layers of the blood-gas barrier were disrupted and erythrocytes could be seen moving into the alveolar spaces. In about half the endothelial and epithelial breaks, the basement membranes remained intact. The average break lengths for both endothelium and epithelium did not change significantly with pressure. The width of the blood-gas barrier increased at 52.5 and 72.5 cmH2O Ptm as a result of widening of the interstitium caused by edema. The cause of the disruptions is believed to be stress failure of the capillary wall. The results show that high capillary hydrostatic pressures cause major changes in the ultrastructure of the walls of the capillaries, leading to a high-permeability form of edema.

Increased fragility of pulmonary capillaries in newborn rabbit

“…However, as Fig. 6 in the earlier report by Tsukimoto et al (12) shows, the lengths of the epithelial breaks were greater than those of the endothelium for all P tm values in the adult lung.…”

“…Therefore, prints of each negative were available for positive identification of structures on the computer screen, as needed, during measurement. This allowed an unequivocal identification of small endothelial and epithelial disruptions as well as the presence (or absence) of basement membrane at all sites of rupture, as was the case with our previous studies (2,12).…”

“…Therefore, at this site, other components of the extracellular matrix, such as type I collagen, cannot play a role. Other evidence of the importance of the basement membranes includes the fact that when stress failure occurs with breaks in the capillary endothelial or alveolar epithelial layers, the basement membranes frequently remain intact (12). In addition, the few measurements that have been made on the ultimate tensile strength of basement membrane indicate that this is very large, presumably because of the presence of type IV collagen (14).…”

“…We conclude that stress failure of pulmonary capillaries in newborn rabbit lungs can occur at Ptm values of less than one-third of those that are required in adult lungs. neonatal lung; lung morphometry; capillary wall stress; stress failure IF THE PULMONARY CAPILLARIES of adult lungs are exposed to transmural pressures (P tm ) that exceed the normal maximal physiological values, ultrastructural changes occur in the walls, and a common result is the development of a high-permeability form of pulmonary edema (12,15). This condition is known as stress failure because it is caused by the high circumferential stresses in the extremely thin capillary walls.…”

Postpneumonectomy pulmonary oedema revisited

“…It has been demonstrated that stress failure occurs more frequently at high than at low lung volumes for a given transmural pressure [28]. There is a spectrum from low-reversible, permeability oedema [29] to high-, probably more irreversible, permeability oedema [30], as the transmural pressure is raised. The fact that previous radiotherapy, for instance, is an independent risk factor for postpneumonectomy pulmonary oedema, suggests that some impairment of the interstitium may also play a role.…”