Role of the fragility of the pulmonary blood-gas barrier in the evolution of the pulmonary circulation.

In 1953 Frank Low published the first high-resolution electron micrographs of the human pulmonary blood-gas barrier. These showed that a structure only 0.3-μm thick separated the capillary blood from the alveolar gas, immediately suggesting that the barrier might be vulnerable to mechanical failure if the capillary pressure increased. However, it was 38 years before stress failure was recognized. Initially it was implicated in the pathogenesis of High Altitude Pulmonary Edema, but it was soon clear that stress failure of pulmonary capillaries is common. The vulnerability of the blood-gas barrier is a key factor in the evolution of the pulmonary circulation. As evolution progressed from the ancestors of fishes to amphibians, reptiles, and finally birds and mammals, two factors challenged the integrity of the barrier. One was the requirement for the barrier to become increasingly thin because of the greater oxygen consumption. The other was the high pulmonary capillary pressures that were inevitable before there was complete separation of the pulmonary and systemic circulations.