To determine the effect of increasing heart rate on mitral flow velocity variables, the time constant of left ventricular isovolumic relaxation and the transmitral pressure gradient, 16 lightly sedated, conscious dogs were studied with Doppler echocardiography during incremental right atrial pacing (n = 16) or the administration of atropine (n = 8) or isoproterenol (n = 8). With increasing heart rate, similar changes were seen with all three interventions and included: 1) mitral flow velocity in early diastole and the early diastolic transmitral pressure gradient either changed minimally or did not change; 2) mitral flow velocity at the start of and as a result of atrial contraction progressively increased; 3) the "absolute" increase in mitral flow velocity and transmitral pressure gradient at atrial contraction demonstrated a biphasic response, initially decreasing as heart rate increased, but then increasing again when atrial contraction occurred in close proximity (less than 70 ms) to mitral valve opening; 3) mitral flow velocity at atrial contraction did not exceed mitral flow velocity in early diastole until atrial contraction was within 70 ms of mitral valve opening and the two velocity peaks were nearly fused; and 4) the largest transmitral pressure gradient and mitral flow velocity occurred at the fastest heart rates, when left atrial contraction preceded mitral valve opening. Major differences among methods included: 1) variable changes in PR interval (+14.2 +- 8.9 ms with atrial pacing versus -74 +/- 26 ms with isoproterenol at peak heart rate compared with baseline); 2) variable changes in the speed of left ventricular relaxation (-2.8 +/- 2.8 ms with pacing versus -7.6 +/- 2.4 ms with isoproterenol at peak rate); and 3) the heart rate at which equalization of mitral flow velocity in early diastole and mitral flow velocity at atrial contraction velocity occurred (128 +/- 12 beats/min with pacing versus 185 +/- 19 beats/min with isoproterenol). These results show that regardless of method, qualitatively similar changes in mitral flow velocity and transmitral pressure gradient occur as heart rate increases. However, for any given heart rate, mitral flow velocity variables and late diastolic pressure gradient can be markedly different, depending on whether atrial pacing, withdrawal of parasympathetic tone or sympathetic stimulation is the cause of the increase in heart rate. These differences among methods appear most related to their effect on PR interval and to a lesser extent the rate of letf ventricular isovolumic relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)

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