This study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF.

Background-To overcome the side effects of amiodarone (AM), its noniodinated analogue, dronedarone (SR), was synthesized. In this study, its electrophysiological effects were compared with those of AM in rabbit hearts. Methods and Results-Five animal groups (nϭ7 each) for 3 weeks received daily oral treatment of 1 of these regimens:(1) control, vehicle only; (2) AM 50 mg/kg (AM50); (3) AM 100 mg/kg (AM100); (4) SR 50 mg/kg (SR50); and (5) SR 100 mg/kg (SR100). ECGs were recorded before drug and at 3 weeks of drug before euthanasia. Action potentials were recorded from isolated papillary muscle and sinoatrial node by microelectrode techniques. The short-term effects were studied in controls (nϭ5) at various concentrations of SR (0 to 10 mol/L) in tissue bath. Action potential duration at 50% (APD 50 ) and 90% (APD 90 ) repolarization and upstroke dV/dt (V max ) at various cycle lengths were compared by ANOVA with repeated measures. Compared with control, AM and SR increased RR, QT, and QTc intervals (PϽ0.0001 for all). Ventricular APD 50 and APD 90 were lengthened by 20% to 49% as a function of dose (PϽ0.005 to Ͻ0.0001) and cycle length (PϽ0.001). SR100 effects were greater than those of AM100 (PϽ0.002). V max was decreased by both AM100 (PϽ0.0001) and SR100 (PϽ0.01). Sinoatrial node automaticity was slowed in treated groups compared with that of the control group (PϽ0.0001 for all). Conclusions-The electrophysiological effects of dronedarone are similar to those of AM but more potent, despite deletion of iodine from its molecular structure, a finding of importance for the development of future class III antiarrhythmic compounds. (Circulation. 1999;100:2276-2281.)

Dronedarone, a noniodinated derivative of amiodarone, is under evaluation as a potentially less toxic anti-arrhythmic alternative to amiodarone. The acute and chronic electrophysiologic effects of dronedarone and amiodarone were compared in isolated rabbit atrial muscle by microelectrode techniques. Four-week PO treatment with dronedarone or amiodarone increased action potential duration (APD90) (58 +/- 4 ms control versus 69 +/- 2 ms dronedarone, p < 0.01; 68 +/- 3 ms amiodarone, p < 0.01 for a 100-mg/kg/d dose) and effective refractory period (49 +/- 6 ms control versus 68 +/- 4 ms dronedarone, p < 0.01; 63 +/- 3 ms amiodarone, p < 0.01). The APD90 prolonged reverse rate-dependency. In contrast, acute superfusion with 10 microM dronedarone or amiodarone decreased APD90 (61 +/- 6 ms control versus 53 +/- 4 ms dronedarone, p < 0.05; 52 +/- 6 ms amiodarone, p < 0.05), effective refractory period (50 +/- 5 ms control versus 44 +/- 4 ms dronedarone, p < 0.05; 43 +/- 6 ms amiodarone, p < 0.05), and the maximum upstroke slope of the action potential (Vmax) (188 +/- 9 V/s control versus 182 +/- 11 V/s dronedarone p < 0.05; 182 +/- 11 V/s amiodarone, p < 0.05). Thus, chronic and acute electrophysiologic effects of dronedarone on rabbit atrial muscle are similar to those of amiodarone, suggesting a similar potential against atrial arrhythmias.

The present study was undertaken to test the hypothesis that the human RR-QT relationship during dynamic exercise differs markedly from that during the recovery phase. Fourteen subjects from the age of 16 to 71 years exercised on a treadmill according to the Bruce protocol. Electrocardiograms were recorded continuously on a magnetic tape, from 1 minute before exercise to 10 minutes into recovery. An exponential formula, proposed by us earlier, closely represented the exercise RR-QT data. However, it was not appropriate for the often S-shaped recovery curves which invariably deviated from the exercise curves, exhibiting hysteresis. Initially, all recovery QT intervals were shorter than the exercise values, but later in the recovery, some crossed the exercise curves from below, resulting in longer QT intervals. The recovery data were fitted by a third degree polynomial, and the hysteresis was calculated as the area between the exercise and recovery curves within a 150 ms range of the RR interval starting from its minimum value. The mechanisms for the occurrence of hysteresis are likely to involve the sympatho-adrenal activity in the early post-exercise period and the time course of QT interval adaptation to rapid changes in the RR interval.

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Phasic red cell velocity and diameters of coronary arterioles, capillaries, and venules were measured in the beating turtle and dog heart using high-speed cinematography with transillumination of the left ventricle. In the turtle, arteriolar red cell velocity was diminished during systole, but during diastole arteriolar inflow increased, especially during the rapid and the slow filling period. Capillary and venule red cell velocity was in-. creased during systole, particularly at the time of ejection; however, during diastole red cell velocity declined and the lowest values occurred during isovolumic relaxation. In dog arterioles, capillaries, and venules, the pattern of red cell velocity was similar. Thus, in the turtle and dog, the peak arteriolar red cell velocity occurred in unison with left coronary artery inflow, and the capillary and venule flow pattern followed that of the coronary sinus. The diameters of arterioles, capillaries, and venules in the turtle ventricle all declined about 34% during systole; similar results were obtained in the dog. Capillary arrangement appeared to be predominantly parallel and cocurrent; however, capillary loops with countercurrent flow were occasionally observed. The data on microvascular phasic red cell velocity are consistent with the macroobservations of reduced coronary artery inflow and enhanced coronary sinus outflow during ventricular contraction. The results demonstrate that the shift in the flow pattern occurs at the transition from arterioles to capillaries. KEY WORDS red cell velocitycardiac cycle arteriolar flow capillary circulation phasic capillary flow venule flow ventricular capillaries countercurrent flow• Rebatel (1) stated in 1872 that "entrance of blood into the smaller coronary vessels during systole is difficult" and that "in diastole the capillaries which have been empty of blood as a result of systolic compression, fill again from larger coronary vessels." Subsequently, numerous other investigators have confirmed the observations that coronary inflow occurs primarily during diastole and that outflow in the coronary sinus takes place mainly during systole (2-8). Consequently, there must be a point where this 180° phase shift occurs (9). However, the exact location of this shift has not been observed directly. In the atrium phasic changes in

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