Classical experiments in whole-body metabolism: closed-circuit respirometry

As part of a series of reviews aimed at providing historical context to the study of whole-body metabolism, this article focuses on the technique of closed-circuit respirometry. Developed by nineteenth century physiologists Henri-Victor Regnault and Jules de Reiset, a constant-pressure closed-circuit calorimeter capable of measuring oxygen consumption and carbon dioxide production in small animals became the framework for future experiments on whole-body metabolism in humans. The volume-loss and volume-replenishment techniques can be used to indirectly assess energy expenditure using an oxygen reservoir; spirometers are simplistic in design but difficult to operate. Leaks, calibration errors, equilibration of gases and dead space are some of the major limitations of the methodology. Despite operational difficulties, closed-circuit respirometry is highly accurate and reproducible. Due to the bespoke nature of many closed-circuit systems, maintenance and repair is often troublesome. Compounded by technological advancement, closed-circuit techniques have become progressively outdated. Nevertheless, the classical experiments in whole-body metabolism played a pivotal role in furthering our understanding of basic human physiology and paved the way for current methodologies used in the field.