Background-Conduction block may be both antiarrhythmic and proarrhythmic. Drug-induced postrepolarization refractoriness (PRR) may prevent premature excitation and tachyarrhythmia induction. The effects of propafenone and procainamide on these parameters, and their antiarrhythmic or proarrhythmic consequences, were investigated. Methods and Results-In 11 isolated Langendorff-perfused rabbit hearts, monophasic action potentials (MAPs) were recorded simultaneously from six to seven different right and left ventricular sites, along with a volume-conducted ECG. All recordings were used to discern ventricular tachycardia (VT) or ventricular fibrillation (VF) induced by repetitive extrastimulation (S2-S5) or 10-second burst stimulation at 25 to 200 Hz at baseline and after addition of procainamide (20 mol/L) or propafenone (1 mol/L) to the perfusate. MAPs were analyzed for action potential duration at 90% repolarization (APD 90 ), conduction times (CT) between the pacing site and the other MAPs, and PRR (effective refractory periodϪAPD 90 ϭPRR) and related to the induction of VT or VF. During steady-state pacing, procainamide and propafenone prolonged APD 90 by 12% and 14%, respectively. Procainamide slowed mean CT by 40% during S2-S5 pacing, whereas propafenone slowed mean CT by up to 400% (PϽ0.001 versus baseline and procainamide). Wavelength was not changed significantly by procainamide but was shortened fourfold by propafenone at S5. Both drugs produced PRR, which was associated with a 70% decrease in VF inducibility with procainamide and elimination of VF with propafenone. Despite this protection from VF, monomorphic VT was induced with propafenone in 57% of burst stimulations. Conclusions-Drug-induced PRR protects against VF induction. Propafenone promotes slow monomorphic VT, probably by use-dependent conduction slowing and wavelength shortening. (Circulation. 1998;97:2567-2574.)

(1) VF vulnerability to monophasic T wave shocks is defined by an AOV that has the shape of a leftward tilted rhomboid. (2) Both the ULV and LLV are sharply defined upper and lower corners of the AOV rhomboid. (3) The width of the AOV corresponds to the dispersion of ventricular repolarization at the 70% level. (4) Considering the dispersion of ventricular repolarization may yield more precise ULV determinations and a better understanding of the correlation between the ULV and DFT.

Dispersion of repolarisation determines vulnerable periods and might be part of the arrhythmogenic substrate promoting induction of VF by T-wave shocks. The coupling intervals of the vulnerable periods depend on the applied shock strength as well as repolarisation, with shock strengths close to the fibrillation threshold inducing VF during dispersion at 90% repolarisation and shock strengths close to the upper limit of vulnerability inducing VF during dispersion at 70% repolarisation. d-Sotalol reduces neither vulnerability to T-wave shocks nor dispersion of repolarisation in this isolated heart model.

Monophasic action potential (MAP) recordings are increasingly being used in a variety of clinical and experimental situations but their manual measurement is cumbersome, especially when hundreds or thousands of beats must be analyzed to monitor the exact time course of action potential duration (APD) changes following heart rate alterations, during surveillance of APD alternans, or during the onset and stabilization of Class III drug effects. To facilitate this task we developed a computer program that automates programmed electrical stimulation, digitizes at 1-kHz sampling frequency MAP recordings up to 8 channels simultaneously, analyzes all APDs at repolarization levels from 10%-90% in 10% decrements (APD10-90), and automatically outputs the analyzed numerical data into spreadsheets for graphical display or statistical analysis. To validate the computer algorithm, two independent observers manually analyzed 585 concurrent MAP recordings at a paper speed of 100 mm/s. Cycle length measurements by the computer were precise to 0.4 +/- 0.5 ms as compared to the computer determined paced cycle length. Computer measurements of APD20, 50, and 90 differed from manual measurements by 2.0 +/- 8.8 ms, 0.7 +/- 7.9 ms, and 0.2 +/- 8.5 ms, respectively, for observer 1; and by 12.2 +/- 8.3 ms, 5.8 +/- 7.5 ms, and 1.4 +/- 10.1 ms, respectively, for observer 2. Inter-observer variability (IOV) was 10.3 +/- 11.1 (APD20), 5.1 +/- 9.0 ms (APD50), and 1.2 +/- 7.8 ms (APD90), which was similar to computer/observer-2 differences and significantly greater (0.001) than computer/observer-1 differences. This indicates that the computer analysis was at least as precise as manual measurements when compared to IOV, and more precise when comparing computer/observer-1 differences to IOV. While providing equal or greater precision, computer-aided analysis of 100 MAP signals took approximately 1 minute while manual analysis of the same data set took between 2.5 and 4 hours. The pacing and analysis software was subsequently applied to experiments that mimic clinically pertinent examples of MAP recordings: (1) automatic generation, analysis, and graphical display of electrical restitution curves at multiple ventricular sites simultaneously; (2) evaluation of myocardial pharmacokinetics by monitoring the progression of Class III antiarrhythmic drug effects by continuous MAP recordings, and displaying differences in drug action between multiple sites; (3) depiction of the adaptation time course of APD to abrupt changes in paced cycle length; and (4) quantitative analysis of APD alternans during myocardial ischemia. The results show that our computerized algorithm greatly facilitates the generation of cardiac electrophysiological, and clinically important, data.