Late Breaking Abstract - Estimation of alveolar surface area by functional morphometry utilising a premature baboon model

Abstract

The main respiratory pathophysiological process following premature birth is delayed or arrested alveolar development, translating to a smaller alveolar surface area (S_A). Histological morphometry is the gold standard method to measure the S_A but can only be applied in deceased individuals. Alternatively, the S_A could be measured in living subjects by “functional morphometry” using Fick’s first law of diffusion and non-invasive measurements of the ventilation perfusion ratio (V_A/Q). We aimed to validate a novel functional morphometric method to measure S_A using a premature baboon model. We utilitised functional morphometry and post-mortem histological morphometry in 11 premature baboons born at 135 days who received intensive care treatment for 14 days. For calculation of the S_A by functional morphology we measured the septal thickness of the respiratory membrane using histology, the alveolar arterial oxygen gradient using concurrent measurements of arterial pressure of O₂ and CO₂ and pulmonary perfusion using echocardiography and integrated Doppler signals. The median (IQR) S_A using functional morphometry was 3,100 (2,080 – 3,640) cm² and using histological morphometry was 1,034 (634 – 1,210) cm² (left lung only). The S_A measured by functional morphometry was not related to the S_A measured by histological morphometry (Spearman’s rho=0.245, p=0.467). Following linear regression analysis, the V_A/Q significantly predicted the histologically measured S_A (R²=0.659, p=0.002). The regression equation was S_A (cm²) = 2,139 x V_A/Q – 75. In conclusion, using a premature baboon model, the ventilation perfusion ratio was the main determinant of the alveolar surface area.