Metabolic studies of the lung

Stubbs, William Albert (1979) Metabolic studies of the lung. University of Southampton, Doctoral Thesis.

Abstract

A new in situ method for rat lung perfusion has been developed. It is simple to perform (thus minimising ischaemic damage), excludes the possibility of the myocardium contributing to perfusion metabolites, produces physiological flow rates and avoids pulmonary oedema for up to 4h without ventilation being necessary. Using this system the utilisation of glucose, alanine, glycerol and lactate was demonstrated with the resultant production of lactate, pyruvate, alanine and glycerol. Small amounts of glucose were also produced probably from lung glycogen. The utilisation of glucose and alanine were concentration dependent and, along with glycerol utilisation , influenced by the nutritional state of the animal. Glucose uptake and metabolite production were also affected by the rate of ventilation of the lung and pCO2 of the perfusate. Lung metabolism was sensitive both acutely and chronically to insulin and corticosterone. The acute effects of these hormones, however, was modified by the nutritional state of the animal and in the lungs from both treated diabetic and ketoacidotic animals the response to insulin was blunted.Rat lungs cleared insulin albeit more slowly than the liver, at a rate dependent on the nutritional state of the animal. Studies in patients with chronic lung disease demonstrated differences in circulating venous blood metabolites which were considered to be independent of treatment or changes in pH and pCO2. These observations in animals and man suggest that the lung is a hormonally responsive organ which could have an important role in whole body metabolism. This concept may be useful in biochemical investigations and could, eventually, modify our approach to certain clinical problems and suggest new approaches to therapy.

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