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Pulmonary artery occlusion pressure and central venous pressure have been considered to be reliable measures of left and right ventricular preload in patients requiring invasive hemodynamic monitoring. Studies in recent years have questioned the correlation between these estimates of ventricular filling pressures and ventricular end-diastolic volumes/cardiac performance variables in specific patient groups, but clinicians have continued to consider the relationship valid in the broader context. The objective of this study was to assess the relationship between pressure estimates of ventricular preload (pulmonary artery occlusion pressure, central venous pressure) and end-diastolic ventricular volumes/cardiac performance in healthy volunteers.Prospective, nonrandomized, nonblinded interventional study.Cardiac catheterization and echocardiography laboratories.Normal healthy volunteers (n = 12 group 1, n = 32 group 2).Pulmonary catheterization and radionuclide cineangiography (group 1) and volumetric echocardiography (group 2) during 3 L of normal saline infusion over 3 hrs.In group 1, the initial pulmonary artery occlusion pressure and central venous pressure did not correlate significantly with initial end-diastolic ventricular volume indexes or cardiac performance (cardiac index and stroke volume index). Changes in pulmonary artery occlusion pressure and central venous pressure following saline infusion also did not correlate with changes in end-diastolic ventricular volume indexes or cardiac performance. In contrast, initial end-diastolic ventricular volume indexes and changes in these ventricular volume indexes in response to 3 L of normal saline loading correlated well with initial stroke volume index and changes in stroke volume index, respectively. The relationship between left ventricular end-diastolic volume index and stroke volume index was confirmed in group 2 subjects using mathematically independent techniques to measure these variables. In addition, initial central venous pressure, right ventricular end-diastolic volume index, pulmonary artery occlusion pressure, and left ventricular end-diastolic volume index failed to correlate significantly with changes in cardiac performance in response to saline infusion in group 1 subjects.Normal healthy volunteers demonstrate a lack of correlation between initial central venous pressure/pulmonary artery occlusion pressure and both end-diastolic ventricular volume indexes and stroke volume index. Similar results are found with respect to changes in these variables following volume infusion. In contrast, initial end-diastolic ventricular volume indexes and changes in end-diastolic ventricular volume indexes in response to saline loading correlate strongly with initial and postsaline loading changes in cardiac performance as measured by stroke volume index. These data suggest that the lack of correlation of these variables in specific patient groups described in other studies represents a more universal phenomenon that includes normal subjects. Neither central venous pressure nor pulmonary artery occlusion pressure appears to be a useful predictor of ventricular preload with respect to optimizing cardiac performance.