Effect of clonidine on cardiac baroreflex delay in humans and rats

Abstract

Cividjian A, Toader E, Wesseling KH, Karemaker JM, McAllen R, Quintin L. Effect of clonidine on cardiac baroreflex delay in humans and rats. Am J Physiol Regul Integr Comp Physiol 300: R949-R957, 2011. First published January 26, 2011 doi:10.1152/ajpregu.00438.2010The delay between rising systolic blood pressure (SBP) and baroreflex bradycardia has been found to increase when vagal tone is low. The ␣2-agonist clonidine increases cardiac vagal tone, and this study tested how it affects . In eight conscious supine human volunteers clonidine (6 g/kg po) reduced , assessed both by cross correlation baroreflex sensitivity and sequence methods (both P Ͻ 0.05). Experiments on urethane-anaesthetized rats reproduced the phenomenon and investigated the underlying mechanism. Heart rate (HR) responses to increasing SBP produced with an arterial balloon catheter showed reduced (P Ͻ 0.05) after clonidine (100 g/kg iv). The central latency of the reflex was unaltered, however, as shown by the unchanged timing with which antidromically identified cardiac vagal motoneurons (CVM) responded to the arterial pulse. Testing the latency of the HR response to brief electrical stimuli to the right vagus showed that this was also unchanged by clonidine. Nevertheless, vagal stimuli delivered at a fixed time in the cardiac cycle (triggered from the ECG R-wave) slowed HR with a 1-beat delay in the baseline state but a 0-beat delay after clonidine (n ϭ 5, P Ͻ 0.05). This was because clonidine lengthened the diastolic period, allowing the vagal volleys to arrive at the heart just in time to postpone the next beat. Calculations indicate that naturally generated CVM volleys in both humans and rats arrive around this critical time. Clonidine thus reduces not by changing central or efferent latencies but simply by slowing the heart. sequences; lag; latency; cardiac vagal motoneurons; ␣ 2-agonist THE GAIN OF THE ARTERIAL baroreceptor-heart rate reflex (cardiac baroreflex) has been calculated from the relationship between spontaneous (10, 13) or drug-induced (47) increases in systolic blood pressure (SBP) and the accompanying decrease in heart rate (HR). In humans, the best correlations were initially obtained by relating cardiac intervals to the preceding SBP (delay ϭ 1 beat) (47), although later studies (14, 38) found a delay of 0 beat was appropriate in subjects with lower initial HRs. In unanesthetized rats, delays of between 2 and 14 beats gave the best correlation for spontaneous baroreflex measurements (35); the best fit for tachycardic responses was 2 to 3 beats longer than that for bradycardic responses (35). The sequence technique of baroreflex sensitivity (sBRS) (13) traditionally uses a constant delay ϭ 1 beat to measure spontaneous baroreflex slope in humans, although the method may be applied using delays of any whole number of beats. This approach has been expanded to give a near-continuous assessment of the slope of the cardiac baroreflex [time-domain cross-correlation BRS (xBRS)] (56). The algorithm of xBRS (56) adjusts in seconds...

Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome

“…27 Clonidine inhibits sympathetic nervous activity and enhances parasympathetic nervous activity, thereby lowering heart rate and blood pressure. 28 In addition, clonidine might have anti-inflammatory properties, 29 as…”

Validity and variability of xBRS: instantaneous cardiac baroreflex sensitivity

“…It was predicted that the time‐averaged values of xBRS would follow the Phe/SNP BRS‐results, that the variance of xBRS would change in relation to its mean level and that reflex delay would increase from 0 to 1 sec at normal resting heart rates to 3–4 sec under atropine and it would decrease to the shortest values at longer resting intervals, under propranolol and clonidine (Cividjian et al. 2011). Finally, we applied a Fourier transform to the sequentially measured BRS‐values to unmask possibly recurrent oscillations in an ostensibly random signal, comparing this to the underlying interbeat interval – and blood pressure signals by cross‐spectral analysis.…”

Dependency Structures in Differentially Coded Cardiovascular Time Series

“…It is changeable according to the physiological state; for example, it is longer in standing than in lying position and it increases with the increase of heart rate and age [20]. Time delay is also affected by a reduction of baroreflex sensitivity, heart failure [21], and syncope [22]. …”

“…Sequences are the streams of consecutive beats in which progressive increases (or decreases) in systolic blood pressure (a SBP ramp) are followed by progressive increases (or decreases) in pulse interval (a PI ramp), delayed by a time lag that heavily depends on species [21–29]. The ramps and streams in physiological time series can be a consequence of physiological interactions and of mere random occurrence.…”