CHARACTERIZATION OF EXCITATION-CONTRACTION COUPLING IN CONSCIOUS DOGSWITH PACING-INDUCED HEART-FAILURE

Objective: In isolated cardiac preparations of non-failing hearts from different species, including man, there is a positive force-frequency relation which is reversed into a negative relation in preparations f rom failing hearts. Whether or not such relations between ventricular function and heart rate hold true in the in situ heart is not clear at present. Mechanical restitution and postextrasystolic potentiation mi ght serve as alternative measures of excitation-contraction coupling, Methods: Eleven dogs were instrumented with a left ventricular microma nometer, ultrasonic crystals for the measurement of regional wall thic kness, two hydraulic occluders around the descending aorta and the inf erior caval vein, and left atrial and ventricular pacing leads with a subcutaneous pacemaker. Left ventricular dP/dt(max), as an isovolumic phase index, and systolic wall thickening, as an ejection phase index, were plotted versus heart rate, and heart rate was increased by left atrial pacing from rest to 200 min(-1) in increments of 25 min(-1). In a subset of dogs, left ventricular filling was controlled and the fre quency range expanded by the bradycardic agent UL-FS 49. Measurements were performed in the presence and absence of autonomic blockade (hexa methonium, atropine). Mechanical restitution and postextrasystolic pot entiation were determined as normalized dP/dt(max) and systolic wall t hickening, respectively, of the extra-and postextrasystolic beat versu s defined variations of the extrasystolic time interval (250-550 ms). Following control studies, heart failure was induced by rapid left ven tricular pacing at 250 min(-1) for 20 days +/- 6 (SD) and measurements repeated. Isolated left ventricular trabeculae from non-failing and f ailing hearts were studied during stimulation at 0.2-4 Hz. Results: On ly with filling control and in the absence of autonomic blockade, was there a slightly positive relation between dP/dt(max) and heart rate i n the control state. Otherwise, the relation of dP/dt(max) to heart ra te was flat both in the control state and in heart failure. The relati on between systolic wall thickening and heart rate in the control stat e was negative, unless fillings was controlled, and it was flat in hea rt failure. In contrast, the time constants of mechanical restitution and postextrasystolic potentiation were increased significantly with h eart failure from 91 +/- 25 (SD) to 164 +/- 13 ms and from 107 +/- 18 to 156 +/- 4 ms, respectively, for dP/dt(max) and from 76 +/- 22 to 16 2 +/- 10 ms and from 101 +/- 17 to 160 +/- 17 ms, respectively, for sy stolic wall thickening. These time constants were, however, insensitiv e to UL-FS 49 and autonomic blockade, There was a negative force-frequ ency relation in left ventricular trabeculae from non-failings hearts at higher calcium concentrations, where it was flat in trabeculae from failings hearts. Conclusion: Time constants of mechanical restitution and postextrasystolic potentiation are more sensitive than the steady state relation of ventricular function and heart rate to characterize the impairment of excitation-contraction coupling in heart failure. ( C) 1998 Elsevier Science B.V.