Multum in parvo: explorations with a small bag of carbon dioxide

A collection of 12 papers published between 1957 and 1972 are revisited. The papers had a common theme of the use of rebreathing carbon dioxide and explored a variety of topics in respiratory physiology. The first study established a method for the noninvasive and indirect estimation of arterial carbon dioxide pressure that was suitable for the routine clinical monitoring of respiratory failure and whose clinical utility remains to this day, but which also provided observations that were the stimulus for the studies that followed. The rate of rise in the partial pressure of carbon dioxide (PCO(2)) during rebreathing led to an analysis of body carbon dioxide storage capacity. Knowledge of carbon dioxide storage led to a method for quantifying lactate production in exercise without the need for blood sampling. The changes in ventilation that accompanied the increase in PCO(2) provided the basis for a rapid method for measuring aspects of breathing control (Read's method), which was later modified to measure the ventilatory response to hypoxia. The physiology of breath-holding was explored through observations of the fall in breath-holding time as PCO(2) climbed. Rebreathing also allowed increases in voluntary ventilation to be achieved without the development of alkalosis, leading to studies of maximal voluntary ventilation and respiratory muscle fatigue. Equilibration of PCO(2) during rebreathing was used to measure mixed venous PCO(2) during exercise and develop an integrated approach to the physiology of exercise in health and disease; alveolar-arterial disequilibrium in PCO(2) during exercise was uncovered. Equilibration of PCO(2), as well as PO(2), during rebreathing of carbon dioxide and nitrogen gas mixtures showed different time courses of venous gases at the onset of exercise. Starting with the rebreathing of carbon dioxide in oxygen mixtures in a small rubber bag, an astonishing range of topics in respiratory physiology was explored, with observations that remain valid, but in some respects unresolved, to the present day.