Noninvasive assessment of alveolar microvascular recruitment in conscious non-sedated rats

• A noninvasive rebreathing method is developed to measure lung function in conscious rats.
• Alveolar microvascular reserves are assessed from the pulmonary diffusing capacity-to-perfusion relationship.
• Small animals show reduced microvascular reserves compared to large species.
• Rats with metabolic syndrome show greater age-exacerbated loss of alveolar microvascular reserves.

Recruitment of alveolar microvascular reserves, assessed from the relationship between pulmonary diffusing capacity (DLCO) and perfusion (Q˙c), is critical to the maintenance of arterial blood oxygenation. Leptin-resistant ZDF fatty diabetic (fa/fa) rats exhibit restricted cardiopulmonary physiology under anesthesia. To assess alveolar microvascular function in conscious, non-sedated, non-instrumented, and minimally restrained animals, we adapted a rebreathing technique to study fa/fa and control non-diabetic (+/+) rats (4–5 and 7–11 mo old) at rest and during mild spontaneous activity. Measurements included O2 uptake, lung volume, Q˙c, DLCO, membrane diffusing capacity (DMCO), capillary blood volume (Vc) and septal tissue-blood volume. In older fa/fa than +/+ animals, DLCO and DMCO at a given Q˙c were lower; Vc was reduced in proportion to Q˙c. Results demonstrate the consequences of alveolar microangiopathy in the metabolic syndrome: lung volume restriction, reduced Q˙c, and elevated membrane resistance to diffusion. At a given Q˙c, DLCO is lower in rats and guinea pigs than dogs or humans, consistent with limited alveolar microvascular reserves in small animals.