The Dickinson W. Richards lecture. New concepts in assessing cardiovascular function.

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Abstract
The primary role of the heart is to provide energy for the circulatory transport of oxygen (O2) to cells at rates commensurate with their metabolic activity. At rest, even a "sick" heart may be capable of transporting O2 adequately. But during exercise, the increase in O2 required by muscle cells demands that their blood flow be increased. The supply of O2 needed to meet the O2 requirement for muscle mitochondrial high-energy phosphate generation during exercise is a critical function of the circulation. Thus, the adequacy of cardiovascular function can be estimated, noninvasively, from the pattern of O2 uptake in response to an exercise stimulus. While arterial O2 tension (PaO2) is dependent on pulmonary function (except for intracardiac right-to-left shunt), the mass transfer of O2 (VO2) between the cells and lungs depends on pulmonary blood flow (i.e., cardiac output) and O2 concentration difference between the pulmonary arterial and pulmonary venous blood, C(a-v)O2 (Fick principle). Thus, VO2 in the first 15 seconds of exercise can be used to describe the initial increase in pulmonary blood flow and stroke volume, while the subsequent rise in VO2 results from the further increase in VO2 in response to work rate increase are used to detect circulatory disturbances. Also, the rate of CO2 output (VCO2) has been valuable in the assessment of cardiovascular function when related to VO2. Inadequate O2 availability results in anaerobic metabolism, causing increased muscle lactic acid production. At the pH of cell water, most of the hydrogen ions produced with lactate are buffered by bicarbonate. The CO2 generated by the buffering reaction (22 ml for each milliequivalent) causes a net increase in VCO2 relative to VO2 at the work rate at which buffering begins. This provides a useful estimate of the anaerobic threshold. Thus, study of the dynamic coupling of external to cellular respiration during a work rate stimulus provides valuable, direct, and noninvasive information about cardiovascular mechanisms in health and disease.