Modulation of rabbit sinoatrial node activation sequence by acetylcholine and isoproterenol investigated with optical mapping technique

AIMS: Changes in the rabbit sinoatrial node (SAN) activation sequence with the cholinergic and adrenergic factors were studied. The correlation between the sinus rhythm rate and the leading pacemaker site shift was determined. The hypothesis concerning the cholinergic suppression of nodal cell excitability as one of the mechanisms associated with pacemaker shift was tested. METHODS: A high-resolution optical mapping technique was used to register beat-to-beat changes in the SAN activation pattern under the influence of the cholinergic and adrenergic factors. RESULTS: Acetylcholine (10 microm) and strong intramural parasympathetic nerve stimulation caused a pacemaker shift as well as rhythmic slowing and the formation of an inexcitable region in the central part of SAN. In this region the generation of action potentials was suppressed. The slowing of the sinus rhythm (which exceeded 12.8 +/- 3.1% of the rhythm control rate) always accompanied the pacemaker shift. Isoproterenol (10, 100 nm, 1 microm) and sympathetic postganglionic nerve stimulation also evoked a pacemaker shift but without formation of an inexcitable zone. The acceleration of the sinus rhythm, which exceeded 10.5 +/- 1.3% of the control rate of the rhythm, always accompanied the shift. CONCLUSIONS: Both cholinergic and adrenergic factors cause pacemaker shifts in the rabbit SAN. While modest changes in the sinus rhythm do not coincide with the pacemaker shift, greater changes always accompany the shift and may be caused by it, according to one hypothesis. The formation of an inexcitable zone at the place where the leading pacemaker is situated is one of the mechanisms associated with pacemaker shift.