Abstract
Abstract
Heart rate variability (HRV) is widely used to characterize cardiovascular autonomic regulation, yet conventional HRV indices are strongly dependent on heart rate (HR). This dependence makes it difficult to determine whether an observed HRV change reflects altered physiological regulation or merely a shift to another operating point along an existing HR–HRV relationship. We investigated this problem using β-adrenergic blockade as a controlled autonomic perturbation and analyzed the resulting changes with a subject-specific heart-rate-dependent Master Curve framework. Seven laboratory canines underwent treadmill exercise under control conditions and following β-adrenergic blockade with metoprolol. Three animals provided ECG recordings of sufficient quality for quantitative Master Curve reconstruction. For each pair of consecutive RR intervals, the successive difference was assigned to the heart rate corresponding to their pairwise mean. The Master Curve was constructed as the heart-rate-specific root mean square of successive RR differences. Repeated control measurements were used to assess within-subject reproducibility, and β-blockade measurements were compared with the subject-specific control reference at matched heart rates. Heart-rate-normalized successive differences and their local variability were also analyzed over time. Repeated control Master Curves showed closely overlapping subject-specific HR–HRV relationships, with substantially smaller within-subject deviations than the changes observed after β-blockade. β-adrenergic blockade produced a systematic downward displacement of the Master Curve in all three animals. At matched heart rates, RMSSD was reduced by 54.7–89.0% relative to the corresponding control reference. Normalized variability also decreased markedly after β-blocker administration, particularly during exercise. These findings demonstrate that β-adrenergic blockade does not merely shift the cardiovascular system along an unchanged HR–HRV relationship but can modify the relationship itself. A mechanistic two-component model suggests that heart rate primarily reflects net chronotropic drive, whereas HRV reflects the magnitude of dynamic regulatory fluctuations around the operating point. The Master Curve therefore provides a physiological reference framework for distinguishing heart-rate-related scaling effects from genuine changes in regulatory variability.