Interacting negative chronotropic effects of adenosine and the vagus nerve on the canine sinus node.

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 mumol.kg-1) was rapidly (less than or equal to 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.(ABSTRACT TRUNCATED AT 250 WORDS)