Interacting negative chronotropic effects of adenosine and the vagus nerve on the canine sinus node
Authors: A. PELLEG, T. MITSUOKA, T. MAZGALEV, E. L MICHELSON
Journal: Cardiovascular Research (1988)

The vagus nerve and adenosine exert a negative chronotropic effect on the mammalian sinus node. In addition, adenosine is released from myocardial cells under both physiological and pathophysiological conditions, which are characterised by variable vagal tone. To determine the interaction between adenosine and the vagus nerve, 21 barbiturate anaesthetised mongrel dogs with bilateral cervical vagotomy and stellectomy were studied. In group 1 (n = 16) adenosine (3 μmol·kg−1) was rapidly (≤ 1 s) administered before (control) and during 60 s of repetitive vagal stimulation. Each stimulus (consisting of a burst of 5 square wave pulses, 0.3 mA in amplitude and 1 ms in duration at 0.1 kHz) was given at a fixed point in time in each sinus cycle (that is, one burst per cycle). This protocol was repeated after a 50 ms incremental change in the phase at which vagal stimulation was given until the entire cycle length was scanned. Recovery time of at least 2 min separated any two consecutive adenosine administrations. In four animals the above protocol was performed twice using vagal stimulation amplitude of 0.3 mA and 0.6 mA in the first and second runs respectively. In this group (group 1), the effect of adenosine was altered by the vagus in a phase dependent manner. In each animal, however, there was at least one phase of the sinus cycle during which vagal stimulation significantly enhanced the effect of adenosine. Adenosine prolonged the baseline mean (SEM) sinus cycle length of 578(24) ms by a maximum of 262(26) ms; during increased background vagal tone, simulated by repetitive vagal stimulation; it prolonged sinus cycle length of 741 (47) ms by 446(45) ms (p<0.02). In addition, an inverse relation was found between background vagal tone and the superimposed action of adenosine. As vagal tone was further increased, the negative chronotropic action of adenosine was decreased (p<0.01). In group 2 (n=5) single bursts (with characteristics as in group 1) were given one at a time, at different phases of the sinus cycle length. The latter were varied in 50 ms increments until the entire sinus cycle was scanned by a single vagal stimulation. This protocol was performed before, during, and after infusions of 2 chloro-adenosine into the sinus node artery. In this group (group 2), adenosine consistently caused an upward and rightward shift of the phasic vagal stimulation-sinus cycle length response curve. Thus, although vagal stimulation prolonged the baseline sinus cycle length of 644(46) ms by a maximum of 383(78) ms in the absence of 2 chloro-adenosine, it prolonged the sinus cycle length of 673(58) ms by a maximum of 617(57) ms in the presence of 2 chloro-adenosine (p<0.05). These results indicate the complex interactive negative chronotropic effects of adenosine and the vagus nerve on the sinus node. Background vagal tone has a modulating effect on the action of adenosine, whereas increased extracellular adenosine concentrations potentiate the depressant action of the vagus nerve on the sinus node.