Aim:
Evaluation of the lung adaptive response to chronic hypoxia might help to elucidate the physiopatological mechanisms leading to the development of severe lung edema and pulmonary hypertension. This study aims in particular to elucidate how hypoxia, a know cause of increase in microvasdcular permeability, affects capillary to interstitium fluid exchanges. Furthermore, we will investigate how a perturbation in microvascular fluid exchange might affect the mechanical interaction between pulmonary capillaries and extracellular matrix.
Methods:
data were obtained from Wistar rats exposed to normobaric hypoxia (10% O2) up to 3 months and on control rats matched for age. Variables measured include:
- pulmonary interstitial pressure (micropipette technique)
- pulmonary artery pressure
- morphometric estimate of air/tissue volume ratio and capillary perfusion index on lungs samples fixed in situ
- determination of mRNA for HIF1, HIF2, VEGF, Endot 1 and FGFb on lung samples
Results:
Within the same animal "well-adapted" (WA) and "mal-adapted" (MA) lung regions co-existed. In WA regions, the lung volume/tissue ratio was 4, similar to control, while in MA regions it decreased to 0.2 to the extension of interstitial and alveolar lung edema. The perfusion index, expressing the volume density of capillaries per unit volume of lung tissue was 0.4 in WA, similar to control, but it decreased four fold in MA. Pulmonary artery pressure averaged 26.2 mmHg ± 2.2 and increased to 39.9 mmHg ± 6 following hypoxia exposure. Pulmonary interstitial pressure averaged 5 cmH2O ± 0.6 and 15cmH2O ± 2 in WA and MA lung regions, respectively. mRNA expression was unchanged, relative to control, in WA regions while HIF1, HIF2, VEGF, Endot 1 and FGFb all doubled in MA regions.
Conclusion:
Lung adaptation to chronic hypoxia shows remarkable regional differences within the same animal. MA lung regions loose the property of being a good gas diffusor due to the edematous conditions that cause loss of alveolar surface area and decrease in perfusion index. The extension of the MA lung regions is a cause of proportional decrease in capillary bed that, in turn, leads to increase in pulmonary vascular resistances and pulmonary artery pressure.