Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol) on parasympathetic and sympathetic activity: a comparison of measures
Abstract
Overview
Background. Cardiovascular autonomic neuropathy (CAN) is recognized as a significant health risk. Specific and
sensitive measures of CAN are needed for early identification and treatment to avoid complications, preferably
in the preclinical state.
Objectives. In this first of two articles, the patient cohort is described and two measures of autonomic function
are reviewed: the traditional heart rate variability (HRV)-alone method and the newer parasympathetic and sympathetic
(P&S) Method. These systems are then evaluated against known effects of the alpha/beta-adrenergic
blocker, Carvedilol, and the selective beta-adrenergic blocker, Metoprolol, on P&S activity.
Methods. Serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory
clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1) introduced,
(2) discontinued or (3) continued without adjustment. Group 3 served as the control. HRV-alone parameters are
computed according to standards. The P&S Method, which is a time–frequency analyses of concurrent respiratory
activity and HRV, is elucidated, as developed at MIT and Harvard Medical School (1981).
Results. The HRV-alone demonstrated that introducing either medication increased low frequency (msec2) and
standard deviation of the beat-to-beat (N-N) interval (msec), as expected. The other HRV parameter responses
were not consistent with expectations. Similar inconsistencies occurred when either medication was discontinued.
The P&S Method demonstrated that introducing or discontinuing either agent decreased or increased
sympathetic activity, respectively, according to expectations. With ongoing treatment, resting parasympathetic
activity decreased with Metoprolol but increased with Carvedilol.
Conclusion. Autonomic assessment fidelity was significantly higher with the P&S Method as validated by comparison
with previously known physiology of the cardiovascular system.
Keywords
Beta-blocker, Cardiac autonomic neuropathy, Heart rate variability, Patient outcomes, Respiratory analysis, Sympathovagal imbalance
Article Information
Disclosure
Financial support: None.
Correspondence
Dr. Joe Colombo 240 South Eighth Street Philadelphia, PA, USA 19107 joe@ans-hrv.com
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