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The oxygen uptake to work rate (VO2/WR) relationship observed throughout peak exercise testing is already being applied for rate adaptive pacemaker programming. However, the detailed curve design of VO2/WR with respect to the anaerobic threshold (AT) has not yet been investigated. It was the purpose of this study to determine the VO2/WR slope below and above the AT in a healthy control group. Seventy-eight healthy control subjects (45.9 +/- 17.4 years; 34 women: 49.9 +/- 18.6 years 44 men: 43.6 +/- 16.6 years) were exercised on a treadmill with "breath-by-breath" gas exchange monitoring using the symptom limited "ramping incremental treadmill exercise" (RITE) protocol. The slope of the VO2/WR relationship from rest to peak exercise (r-p), rest to AT (slope A), and AT to peak exercise (slope B) in mL oxygen uptake per watt of external treadmill work was determined by linear regression analysis. [table: see text] The oxygen uptake to work rate relationship throughout peak exercise in the entire study group generated a significant slope change at the AT (31%, P < 0.0001) with a decreasing slope during higher work load intensities. Female subjects demonstrated a greater percentage of slope change at AT (43%), as compared to men (22%, P < 0.01). When using the oxygen uptake to work rate relationship for the programming of the pacemaker's rate response to exercise, the significant slope change at the AT should be considered to more appropriately pace during higher work intensities supported by anaerobic metabolism. Female pacemaker patients should be programmed to generate a steeper VO2/WR slope below AT with a greater slope change at AT, as compared to men. Abnormally high oxygen uptake to work rate ratios above the AT may be possibly used as an indicator of overpacing.