Origin, domain, and dynamics of rate-induced variations of functional refractory period in rabbit atrioventricular...

Different aspects of the intrinsic regulation of rate-induced variations of functional refractory period of atrioventricular node (FRPN) were studied in isolated rabbit heart preparations. First, the hypothesis that these variations originate from the net interaction between facilitation and fatigue was tested. For a constant fast rate, selective effects of faciliation and of steady-stage fatigue were independently shown to shorten and prolong, respectively, FRPN while their combined effects were shown to result in intermediate changes corresponding to the sum of their individual effects. Second, selective and combined effects on FRPN were shown to start for rates corresponding to the upper half of the 1:1 nodal conduction range and to reach their maximums at the fastest rate tested. Third, the time-courses of fatigue-induced prolongations in nodal conduction time and FRPN were shown to be closely linked. Facilitation effects on conduction time and FRPN were confirmed, as previously shown for in situ dog hearts, to be linked, but time-independent. Fourth, FRPN was shown not to correspond to particular limits in its subintervals, but to be, nevertheless, related to nodal refractoriness. Fifth, it was demonstrated that, in conditions of combined facilitation and transient fatigue such as those prevailing in current endocavitary investigations of nodal function, FRPN could be shortened, left unchanged or prolonged by a constant fast rate depending on its duration. In conclusion, the present study demonstrates the dual origin of rate-induced FRPN variations, their rate and time dependence, their relation to changes in nodal refractoriness, and their involvements in various nodal responses.