Cardiac pacemaker activity interacts with cardiac mechanical activity. Pacemaker impulses repetitively induce contractions in atrial muscle cells. Oscillating atrial mechanical activity, in turn, effects the generation of pacemaker cell impulses. The frequency of pulsations in the sinus node artery that normally courses through the midst of the sinus node has been implicated in regulation of pacemaker firing rate. To elucidate the mechanisms for these mechano-electrical feedback loops, the following hypotheses will be tested: 1) Phasic variations in atrial tension can stimulate sinus node pacemaker cell action potentials. 2) Phasic variations in sinus node artery pressure can stimulate sinus node pacemaker cell action potentials. 3) The levels of mean atrial and mean arterial pressure determine whether phasic mechanical events and pacemaker impulses can interact. 4) Changes in atrial pressure or sinus node artery pressure alter electrotonic spread within the sinus node. 5) Electrical activity propogates between arterial muscle cells and sinus node pacemaker cells. This study is made feasible with the isolated, arterially perfused canine right atrium. The use of microelectrodes in the sinus node and the stimultaneous measurements of pressures within the sinus node artery and right atrium will allow a direct approach to each hypothesis. Diseases that alter connective tissues, arteries, or pressures within the heart can disrupt the mechanisms that regulate stable pacemaking. Mechano-electrical feedback between the right atrium or sinus node artery and the sinus node has received some experimental attention, but the cellular mechanism is poorly understood. The proposed project aims to close this gap in our knowledge by studying each component of the feedback loops under physiologic conditions while the other components are carefully controlled.
