Repolarization Inhomogeneities in Ventricular Myocardium Change Dynamically With Abrupt Cycle Length Shortening

BackgroundIn single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized. Methods and ResultsTo determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium ofventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using highresolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 ± 3 msec, p < 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 + 13.3 to 76 + 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 ± 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (−51.0 ± 6.8%, p < 0.01) by the sixth post-CL shortening beat and then recovered (by 15–20 beats). In contrast, DI failed to decrease during hypoxia (+ 7.1 + 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient. ConclusionsThese data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias.

[1]  B. Hoffman,et al.  Effect of heart rate on cardiac membrane potentials and the unipolar electrogram. , 1954, The American journal of physiology.

[2]  G. Moe,et al.  Nonuniform Recovery of Excitability in Ventricular Muscle , 1964, Circulation research.

[3]  C. Fisch,et al.  Effect of Cycle‐Length Alteration upon the Configuration of the Canine Ventricular Action Potential , 1966, Circulation research.

[4]  C. Fisch,et al.  Effects of cycle-length alteration on canine cardiac action potentials. , 1967, The American journal of physiology.

[5]  M. J. Janse,et al.  Refractory Period of the Dog's Ventricular Myocardium Following Sudden Changes in Frequency , 1969, Circulation research.

[6]  I. Mirsky,et al.  Left ventricular stresses in the intact human heart. , 1969, Biophysical journal.

[7]  B Lown,et al.  Approaches to Sudden Death from Coronary Heart Disease , 1971, Circulation.

[8]  D. Noble,et al.  The dependence of plateau currents in cardiac Purkinje fibres on the interval between action potentials , 1972, The Journal of physiology.

[9]  H. Wellens,et al.  Electrical Stimulation of the Heart in Patients with Ventricular Tachycardia , 1972, Circulation.

[10]  R. Lazzara,et al.  Disorders of Cellular Electrophysiology Produced by Ischemia of the Canine His Bundle , 1975, Circulation research.

[11]  B. Surawicz,et al.  Sequence of repolarization on the ventricular surface in the dog. , 1975, American heart journal.

[12]  G. Salama,et al.  Merocyanine 540 as an optical probe of transmembrane electrical activity in the heart , 1976, Science.

[13]  M. Burgess,et al.  Electrotonic Interaction during Canine Ventricular Repolarization , 1978, Circulation research.

[14]  J. Toyama,et al.  Effects of verapamil on canine Purkinje fibres and ventricular muscle fibres with particular reference to the alternation of action potential duration after a sudden increase in driving rate. , 1979, Cardiovascular research.

[15]  G. Salama,et al.  Optical probes of membrane potential in heart muscle. , 1979, The Journal of physiology.

[16]  Effects of hypoxia or low PH on the alternation of canine ventricular action potentials following an abrupt increase in driving rate. , 1980, Cardiovascular research.

[17]  B. R. Jewell,et al.  Analysis of the effects of changes in rate and rhythm upon electrical activity in the heart. , 1980, Progress in biophysics and molecular biology.

[18]  M. Josephson,et al.  Termination of ventricular tachycardia: role of tachycardia cycle length. , 1982, The American journal of cardiology.

[19]  A. Michelucci,et al.  Atrial refractoriness and spontaneous or induced atrial fibrillation. , 1982, Acta cardiologica.

[20]  B. Surawicz,et al.  Characteristics and Possible Mechanism of Ventricular Arrhythmia Dependent on the Dispersion of Action Potential Durations , 1983, Circulation.

[21]  M Akhtar,et al.  Facilitation of ventricular tachycardia induction with abrupt changes in ventricular cycle length. , 1984, The American journal of cardiology.

[22]  P M Rautaharju,et al.  Ventricular action potentials, ventricular extracellular potentials, and the ECG of guinea pig. , 1985, Circulation research.

[23]  P. Tchou,et al.  Effect of sudden rate acceleration on the human His-Purkinje system: adaptation of refractoriness in a dampened oscillatory pattern. , 1986, Circulation.

[24]  F. Marchlinski.  Characterization of oscillations in ventricular refractoriness in man after an abrupt increment in heart rate. , 1987, Circulation.

[25]  G. Salama,et al.  Maps of optical action potentials and NADH fluorescence in intact working hearts. , 1987, The American journal of physiology.

[26]  M. Franz,et al.  Cycle length dependence of human action potential duration in vivo. Effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady-state frequencies. , 1988, The Journal of clinical investigation.

[27]  J. C. Bailey,et al.  Alternans of Action Potential Duration After Abrupt Shortening of Cycle Length: Differences Between Dog Purkinje and Ventricular Muscle Fibers , 1988, Circulation research.

[28]  M. Simson,et al.  Oscillations of conduction, action potential duration, and refractoriness. A mechanism for spontaneous termination of reentrant tachycardias. , 1988, Circulation.

[29]  J. C. Bailey,et al.  Action potential duration alternans in dog Purkinje and ventricular muscle fibers. Further evidence in support of two different mechanisms. , 1989, Circulation.

[30]  M. Antz,et al.  Slow and long-lasting modulation of myocardial repolarization produced by ectopic activation in isolated rabbit hearts. Evidence for cardiac "memory". , 1989, Circulation.