To investigate the utility of body surface isochrone maps for estimating ventricular arrhythmias in patients with previous myocardial infarction, we compared findings of body surface isochrone maps with those of signal-averaged electrocardiograms (SAECGs) and an incidence of ventricular tachycardia (VT). body surface isochrone mapping was performed in 50 patients with previous myocardial infarction. Eighty-seven unipolar electrocardiograms distributed over the patient's anterior chest and back were recorded simultaneously. For each lead, the activation time was measured as the duration from the onset of QRS to the peak of the R wave. SAECGs were recorded in the same patients to detect late potential (LP) which was found in 31 of 50 patients. The group D+ had a lower ejection fraction and higher incidence of VT (8/31 (25.8%) vs. 1/19 (5.3%)) and LP (13/31 (41.9%) vs. 2/19 (10.5%)) than the group D-. There were four patients with sustained VT who had both D and LP. For predicting VT, D has a sensitivity of 88.9% and a specificity of 43.8%. It was decided that abnormal delay on body surface isochrone maps indicates slow conduction of the surviving myocardium and is related to the occurrence of ventricular arrhythmias. We concluded that body surface isochrone maps can be useful in predicting life-threatening arrhythmias in patients with previous myocardial infarction.

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We retrospectively compared the efficacy of percutaneous transluminal coronary angioplasty (PTCA) and intracoronary thrombolysis (ICT) in patients with acute myocardial infarction (AMI). The ICT group consisted of 62 consecutive patients who underwent ICT before the introduction of PTCA for AMI and who were considered to be candidates for PTCA based on review of their cine-films. The PTCA group consisted of 92 consecutive patients who underwent PTCA thereafter. The reperfusion rate was significantly higher in the PTCA group than in the ICT group (92.4% vs 71.4%, < 0.01) and the residual stenosis was significantly lower in the former. Furthermore, the incidences of reinfarction and post-infarction angina were significantly lower in the former than in the latter (3.3% vs 12.9%, p < 0.05 and 6.5% vs 29.0%, p < 0.001 respectively). Although the degree of improvement in left ventricular function was influenced by the result of reperfusion, it was not improve left ventricular function method. Therefore, PTCA did not improve left ventricular function more than ICT unless ICT alone failed to achieve reperfusion.

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Regional blood flow in the liver, pancreas and kidney was measured under conditions of profound hypothermia associated with total circulatory arrest, to determine whether cardiopulmonary bypass with pulsatile flow would improve the blood flow in these visceral organs in comparison with nonpulsatile flow. Using 56 adult mongrel dogs, total cardiopulmonary bypass was carried out to induce hypothermia and 40 min of total circulatory arrest was performed at 20°C. After total arrest, the temperature was raised to 35°C. With pulsatile flow, a decrease of the regional blood flow in the liver, pancreas and kidney was prevented during cooling, especially at 20°C before total circulatory arrest. Moreover, regional renal blood flow recovered rapidly with pulsatile flow after total arrest at 20°C, while after arrest with nonpulsatile flow blood flow in the kidney could not be measured in the cortex and was significantly lower in the medulla. In summary, pulsatile flow improves the hepatic, pancreatic and renal blood flow and, referring to our previous experiments, protects the function of these organs during cardiopulmonary bypass associated with profound hypothermia and total circulatory arrest.

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The effects of seven Class-I antiarrhythmic drugs on the maximum upstroke velocity (V^^·max) of action potential were examined in isolated guinea pig ventricular muscles in order to characterize their use- and state-dependent sodium channel blocking action. From the onset and offset kinetics of the use-dependent V^^·max inhibition during stimulation trains, the seven drugs were subdivided into two groups; fast drugs (lidocaine, mexiletine, and tocainide), and slow drugs (quinidine, aprindine, disopyramide and flecainide). In experiments to assess the state-dependent sodium channel block, a conditioning clamp pulse to 0 mV was applied by using the single sucrose-gap voltage-clamp technique, and the Vmax of test action potential 100 msec after the clamp pulse was measured. The decrease in V^^·max by 10 msec clamp pulse was defined as the activated channel block (ACB), and the decrease in V^^·max as the clamp pulse duration was prolonged from 10 to 500 msec was defined as the inactivated channel block (ICB). The ratio of ICB to ACB was less than 1.0 for quinidine, disopyramide and flecainide, and much greater than 1.0 for aprindine, lidocaine, mexiletine, and tocainide. These characteristics may contribute to the differences in efficacy of each drug in treating various types of arrhythmias.

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The effect of several class I antiarrhythmic drugs (aprindine, cibenzoline, disopyramide, mexiletine, lidocaine, tocainide and 711389-S) were studied on slow Ca²⁺ channels of rabbit sinus node cells using a double microelectrode voltage clamp technique. All these drugs decreased the heart rate, the maximum rate of rise (V^^·max), the action potential amplitude and the slope of the phase 4 depolarization in spontaneously beating sinus node preparations. The order of inhibitory potency on the heart rate was: aprindine > 711389-S > cibenzoline &ges; disopyramide > mexiletine &ges; lidocaine > tocainide. On the current systems, these drugs decreased the slow inward current (I^si) and the time-dependent potassium current (I_k). However, the major effect was a reduction of I_si. These agents also exerted a frequency-dependent block of I_si. furthermore, comparing the effects of class I antiarrhythmic agents on slow Ca²⁺ channels, the order of inhibitory effects on V^^max of sinus node cells was: aprindine > 711389-S > cibenzoline &ges; disopyramide > mexiletine > tocainide. These electrophysiological observations suggest that class I antiarrhythmic drugs have a depressant effect on slow Ca²⁺ channels as well as fast Na⁺ channels of myocardial cells, and that so-calledslowkinetic drugs may depress slow Ca²⁺ channels more strongly thanfastkinetic drugs.

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We evaluated the effects of antiarrhythmic drugs on ventricular fibrillation threshold (VFT) by analysing the electrophysiologic parameters obtained from strength-interval curves. The VFT determined by low intensity train pulses was significantly increased from the control value under the administration of clinical dosage of clinical dosage of procainamide, lidocaine, propranolol, bepridil and prenylamine, although not verapamil. The elevation of VFT could be explained by changes in the strength-interval curve induced by the drugs, including disappearance of dip phenomenon, supernormal period, prolongation of effective refractory period (ERP) and elevation of end diastolic threshold (EDT).

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The role of electrophysiologic parameters on the induction of ventricular fibrillation (VF) by continuous 50 cycle per second (cps) electrical stimulation was studied in 21 open chest dogs. The current strength of the 50 cps stimulation required to induce VF when applied to the ventricle for 2 seconds was defined as the ventricular fibrillation threshold (VFT). The intravenous injection of antiarrhythmic drugs raised the VFT in a dose dependent manner. The changes in VFT were associated with a rise in excitation threshold. The slopes of the regression equations relating the excitation threshold to VFT were almost identical, that is, 2.8 with lidocaine, 3.4 with procainamide and 3.2 with disopyramide. Prolongation of refractory period increased the cycle length of ventricular excitations just prior to VF but was not correlated with the changes in VF. Localized myocardial ischemia induced by coronary ligation also resulted in the elevation of VFT. The slope of the regression equation between excitation threshold and VFT was 1.9 which was slightly lower than that observed at the administration of the drugs. The fact that the VFT was mainly attributed to the changes in excitation threshold at the site where the test stimulus was applied would limit the usefulness of the 50 cps continuous stimulation method for the evaluation of vulnerability to VF.

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Mechanisms by which Class I drugs interrupt or facilitate reentrant ventricular tachycardia (VT) induced by programmed stimulation were analysed in dogs with 7-day-old myocardial infarction. Activation time and effective refractory period (ERP) were determined at 48 sites of survived epicardial layer within the infarction zone (IZ) and surrounding normal zone. Two mg/kg of lidocaine (L), propafenone (P) and flecainide (F) were administered intravenously. Induction of sustained VT was prevented by P in 7 of 10 cases, in 3 of 5 cases by F and in one of 8 cases by L (P vs L, p < 0.01). Proarrhythmic effects were encountered in a case of P and w cases of F. Conduction velocity within the IZ was reduced by each drug to the same extent. The ERP within the IZ was prolonged by each drug, However, the mean extent of change differed significantly among the drugs (P 37% > F 26% > L 10%). In cases in which an antiarrhythmic effect was achieved, it was the result of abolition of the re-excitation at retrograde exit site of reentry circuit, which was considered to be due to prolongation of refractoriness at the site. These results suggest that prolongation of local refractoriness within the IZ is the major antiarrhythmic mechanism. The proarrhythmic effect was accompanied by an increased dispersion of local ERP as well as by a marked reduction of conduction velocity within the IZ.

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The effects of procainamide and lidocaine, representative of class IA and IB antiarrhythmic agents, on electrically inducible ventricular tachycardia (VT) were studied using programmed ventricular stimulation in 47 post myocardial infarction patients at an average of 1.5 months after the onset. The mean doses of administered procainamide and lidocaine were 1050 mg and 161 mg, and their mean plasma concentrations were 7.5μg/ml and 3.1μg/ml respectively. The induction of sustained VT was suppressed in 15 of 29 patients (52%) by procainamide, but in none by lidocaine. The induction of nonsustained VT was suppressed in 6 to 18 patients (33%) by procainamide, and in 1 of 8 patients (13%) by lidocaine. The efficacy rate of procainamide was significantly higher than that of lidocaine in suppression of VT induction (21/47 vs 1/14 p > 0.01). Procainamide significantly prolonged the effective refractory period of the right ventricle as well as the HV and QRS interval, however lidocaine did not affect them significantly. On the other hand, the worsening effect which changed nonsustained VT inducible in the baseline into sustained VT inducible post drug administration was demonstrated in 8 of 18 procainamide cases (44%), and in 3 of 8 lidocaine cases (38%). Between the procainamide effective and ineffective or worsening patients, there were to differences found in the electrophysiologic variables either in the baseline or post procainamide administration. We concluded that procainamide was more effective than lidocaine for the prevention of potential life-threatening VT induction in post myocardial infarction patients, although its efficacy was considerably limited, and to confirm the effectiveness and exclude the worsening effects of the class IA and IB antiarrhythmic agents, drug testing using programmed ventricular stimulation appeared to be valuable.

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In 24 patients with idiopathic ventricular tachycardia (VT), mechanisms of VT and the effects of antiarrhythmic drugs after induction were studied electrophysiologically, and by exercise testing. VT was induced electrophysiologically in 14 patients. Class 1 antiarrhythmic drugs were effective in 7 of them, which implied that one of the mechanisms of idiopathic VT was reentry related to the depressed channel dependent slow conduction. In 6 of the 14 patients, the QRS morphology of VT showed a complete RBBB with axis deviation pattern and the tachycardia was responsive to verapamil. In 2 of them, induction of VT was facilitated at low plasma verapamil concentrations. In the other 2 patients, left ventricular mapping showed that a notched potential preceding each QRS complex and the retrograde His bundle deflection with a short interval were recoded during VT. These findings suggested that the mechanism of this type of VT was reentry, mediated by Ca dependent slow conduction and located within the left bundle branch network. Exercise testing provoked VT in eight. Beta-blockers and Ca-antagonists were effective in 6 and in 4, respectively. These findings indicate the possibility that in addition to enhanced automaticity or reentry, triggered activity could play a role in the genesis of exercise related VT.

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Ninety-eight cases of ventricular tchycardia (VT) were studied using clinical electrophysiological (EP)-pharmacological assessment to compare the efficacy of class IA (disopyramide-DP, procainamide-PA) and class IB (mexiletine-Mex, Lidocaine-Lid, aprindine-AP) agents available in Japan, and to evaluate the clinical significance of class subdivisions for the treatment of VT. In assessing the efficacy of drugs, we evaluated their ability to prevent and terminate induced sustained VT as well as their ability to suppress spontaneous premature ventricular beats (VPB). I. EP properties: DP significantly extended QTc, ERP_RV, and the coupling interval by which VT or repetitive ventricular response (RVR) was induced. On the other hand, Mex and A had no effect. Although no significant extention of QRS width was found, the significant extension of the interval from extrastimulus to the first induced VT or RVR complex by the three drugs indicates that all have suppressive effects on conduction velocity within the reentry circuit. II. Clinical significance: Correspondence of preventive effects was 67% for DP and PA (class IA), 54% for Mex and Lid (class IB), 55% for DP and Mex, 27% for PA and Mex, and 25% for PA and DP. Correspondence of terminating effect was 85% for DP and PA, 80% for DP and PA, 77% for DP and Mex, 75% for Mex and Lid, and 63% for Mex and PA. For suppression of spontaneous VPB's, correspondence rate was 100% for DP and PA, 39% for DP and Mex, 64% for Mex and Lid, 61% for Mex and PA, and 69% for DP and PA. EP properties of class IA and IB drugs, as assessed by ECG and EP studies, agreed with their EP properties in normal isolated cardiac tissue. However, we were unable to discern a clear difference in clinical efficacy between class IA and IB drugs in this study. Our results indicate that IA and IB drugs differ little in prevention and termination of sustained VT, and that PA possesses qualities that set it apart from other IA and IB drugs. Accordingly, limitations of the Vaughan Williams classification system must be kept in mind using it as a reference for drug selection in the clinical treatment of VT.

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A retrospective analysis of 44 patients was carried out to evaluate the efficacy of class IA antiarrhythmic drugs ( disopyramide and/or procainamide), and of drugs of one or more other classes by means of 24-hour Holter recording. This study included only patients who exhibited 5000 or more ventricular premature complexes (VPCs) during a 24-hour pretrial baseline recording. The drugs that reduced the frequency of VPCs by at least 50% were considered effective. Eighteen patients (41%) responded to class IA drugs (respoders) and 26 patients (59%) did not (nonresponders). There was a significant difference between the two groups in relation to the types of disease (p < 0.01), but no significant difference with regard to other clinical and electrocardiographic characteristics. There was a significant discordance between trials of class IA drugs and class IC drugs (p < 0.05). The efficacy of class IA drugs is very similar to that of class IB drugs, and only class IC drugs represent the highest efficacy in patients refractory to both class IA and class IB drugs. In conclusion, when ventricular arrhythmias do not respond to class IA or IB drugs, class IC drugs could be chosen as the next regimen.

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The efficacy of disopyramide (DP), mexiletine (MX), aprindine (AP) and cibenzoline (CZ) on ventricular arrhythmias was compared (single drug therapy). In addition, the efficacy of the combination therapy of DP with MX was also studied (combination therapy). One hundred of the 106 patients completed the protocol of the single drug therapy. Fifty percent or more reduction in the frequency of ventricular premature contractions (VPCs) was obtained in 24 of 43 patients (56%) with DP, in 24 of 44 (55%) with MX, in 18 of 29 (62%) with AP and 10 of 18 (56%) with CZ. AP was comparatively more effective than the other drugs tested. DP was significantly effective on VPCs with organic heart disease as compared to idiopathic VPCs with organic heart disease as compared to idiopathic VPCs (p < 0.05), while the other 3 drugs did not have such a tendency. With MX therapy, 10 of the 12 patients with fast VT rate (&ges; 150 beats/min) showed a significant effect while only 4 of the 12 patients with non-fast VT rate (&ges; 100 and 150 beats/min) had a significant one (p < 0.05). On the other hand, DP, AP and CZ showed almost the same efficacy at any cycle length of VT. Six patients withdrew from the study, 4 because of digestive troubles with MX therapy, 1 because of micturition disturbances with DP and 1 because of skin rash with AP. The average therapeutic plasma levels of DP, MX AP and CZ were 1.76 0.54 g/ml, 1.08 0.43 g/ml and 268.2 123.3 ng/ml, respectively. Consequently, compared to western patients, as indicated by the liberature, Japanese Patients needed only the half of the dosage and two thirds of the plasma levels to achieve almost the same efficacy. The combination therapy of DP (50 mg t.i.d.) with MX (100 mg t.i.d.), which was administered in 20 patients during hospitalization, showed approximately the same efficacy as DP (100 mg t.i.d.) or MX (150 mg t.i.d.) therapy alone, while the incidence of side effects in the combination was lower than that in DP or MX therapy alone. That is, the incidence was only 1 of the 20 patients (5%) with the combination of DP with MX, compared to 4 of 18 (22% with MX alone and 2 of 16 (13%) with DP alone. Therefore, it may be expected that combined therapy can reduce the degree of side effects with its lower dosage than the conventional dosage of each drug while retaining the same degree of efficacy as single drug therapy.

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