An assessment of the acute hemodynamic effect of intravenous isosorbide dinitrate (ISDN) as performed with a Mikro-tip^(R) angiocatheter in 10 patients during the diagnostic cardiac catheterization. Both left ventricular (LV) systolic pressure (SP) and end-diastolic pressure (EDP) were decreased by 2 mg of ISDN. Cardiac index, stroke work index and heart rate did not change significantly, and neither systemic vascular resistance nor pulmonary arteriolar resistance was reduced. Isovolumic phase and ejection phase indices of contractility were not altered. End-diastolic stress, and accurate index of preload, was reduced significantly (47.0 ± 27.6 to 28.7 ± 24.6 g/cm², p < 0.01), and mid-systolic stress, an index of afterload, was also reduced (371 ± 102 to 332 ± 85 g/cm², p < 0.05). No undesirable side effects were noted during this study. We concluded that bolus intravenous (IV) ISDN safely reduced both preload and afterload. As 2 mg of IV ISDN had no significant change on SVR, a larger dose of ISDN bolus injection might be needed for a significant arterial vasodilating effect. Bolus IV ISDN seems to be very effective in case in which rapid reduction of LV filling pressure is mandatory.

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Hemodynamic effects of a new inotropic agent, OPC-8212 (2(1H)-quin-olinone derivative) were studied in anesthetized open chest dogs pretreated with propranolol and diltiazem .Three doses (1, 3 and 10 mg/kg) of OPC-8212 were administered intravenously and the net hemodynamic effect (% change) was obtained by subtraction of the effect of the solvent from the gross effect, since the vehicle has a transient, but significant hemodynamic effect. The maximal inotropic effect occurred 3 minutes after administration: LV dP/dt max and cardiac output (CO) increased by 19 ± 2.5% and 28 ± 8.5%, respectively, at 3 mg/kg. These cardiotonic effects were dose-dependent, whereas heart rate, peak LV pressure (PLVP) and mean aortic pressure were minimally changed at any dose. Accordingly, systemic vascular resistance (SVR) decreased in a dose-dependent manner although the decrease was much less than that in administration of isoproterenol. The inotropic effect was not blocked by β-adrenoceptor blockade (propranolol 1 mg/kg), indicating that the cardiotonic action of this agent is not due to β-adrenergic stimulation. Thus, this agent could reverse β-blocker-induced heart failure. During infusion of diltiazem (0.1 mg/kg/min following bolus intravenous administration of 0.5 mg/kg), the increases in LV dP/dt max and CO due to OPC-8212 were similar to those in the control study. In contrast to the effects under β-adrenoceptor blockade, however, decreased PLVP was restored by OPC-8212. Neither chronotropic nor rrhythmogenic effects were observed in the control or with either pharmacological intervention. These results indicate that OPC-8212 has a potent inotropic action with modest vasodilatory effect even with propranolol or diltiazem pretreatment. Thus, OPC-8212 can be used in combination with β-adrenoceptor antagonists and Ca⁺⁺-channel blockers, and also can reverse the heart failure induced by mismanagement of these cardio-depressant agents.

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Five among 19 cases of sustained ventricular tachycardia (VT) treated in the last two years had left ventricular aneurysms, but the patients denied any previous attack of chest pains that would indicate acute myocardial infarction. Laboratory findings including serum electrolytes were normal and no signs of inflammation were found. Coronary angiograms were normal but the left ventriculograms showed aneurysms in four patients and akinetic to aneurysmal wall motion in one patient. Electrophysiologic studies (EPS) were done in four patients. VT was induced reproducibly by programmed electrical stimulation in three patients and it was terminated by programmed stimulation within 30 seconds. The foci of VT were determined by EPS. One case who showed acceleration of the VT rate following the second induction of VT developed a fulminant course; Adams-Stokes attacks from VT, more than ten times a night in spite of intravenous administration of a large dose of procainamide, were terminated by DC shock. VT as determined to originate from the aneurysm that was resected operatively. In the other two cases, the foci were resected and the intraoperative EPS confirmed the preoperative foci. The postoperative EPS showed no inducibility of VT in three surgical cases. Though the induction of VT may not be indicated in every case of VT, we believe that EPS is required to determine the focus for the operation and to evaluate the precise drug efficacy in rapid VT. It is further stressed that the sustained VT of our patients including the present five, lasted for several hours until it was terminated in the hospital.

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To evaluate the role of perinodal tissue in the genesis of atrioventricular (AV) nodal reentry, echo beats were induced by programmed stimulation in nine superfused rabbit AV nodal preparations which included the crista terminalis (CT) input, interatrial septal (IAS) input and perinodal atrial tissues in addition to the AV node. Two patterns of AV reentry were observed: 1) In six preparations, premature response was blocked within the AV node, but anterograde conduction continued along the perinodal fibers and entered the AV node by way of another input region. Reentry occurred via retrograde nodal conduction to the initial input and subsequently conducted within the perinodal region. 2) In three preparations, premature beat elicited by CT stimulation was blocked in the perinodal tissues near the CT, conducted slowly in an anterograde fasion through the AV node. To complete the reentry circuit, it exited at the IAS region and conducted in retrograde fashion via the perinodal tissues to reenter the node at the CT. Moreover, in four other preparations, surgical interruption of the perinodal tissue prevented reinitiation of reentrant phenomena. Thus, the critical role of the perinodal tissues as a necessary link in AV nodal reentry was demonstrated in this preparation.

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Mechanisms of ventricular tachycardia induced by local application of a properly timed premature stimulus were studied with routine microelectrode technique and extracellular recordings on a ventricular sheet. Thinly sliced preparations obtained from subepicardial muscle of the canine ventricle were used as an approximation of a two-dimensional model. On these preparations, spontaneously sustained tachycardia easily induced by a single premature stimulus. Since delayed after-depolarizations were never evoked by frequent stimulations even in the K⁺-free and high-Ca⁺⁺ media, these tachycardias seemed to be induced by re-entrant and circus movement mechanisms. To analyse the re-entrant mechanisms, action potentials generated by normal driving stimuli were recorded from multiple points (40∼50 points) and the spreads of the depolarization and repolarization phases of the action potentials were mapped. The depolarizing wave front on the map always showed a circular or elliptical pattern. Whenever the pattern of spread of the repolarizing wave was similar to that of the depolarizing wave, sustained tachycardia was never brought about by any premature stimulus. On the other hand, when the map of the spread of the repolarizing wave was very complicated and mixed with that of the depolarizing wave, sustained tachycardia was frequently induced. From the above results, it is suggested that the nonuniform recovery of excitability plays a role in the generation of sustained tachycardia. Moreover, a portion of the unidirectional block of the premature impulse was determined by calculated using the conduction velocity of the premature impulse and the effective refractory period in each cell; then a route of re-entry for the premature impulse was simulated. In additional experiments, tachycardia was always suppressed by lidocaine, but was not suppressed by verapamil. The suppression mechanism of lidocaine appeared to be to bring nonuniform recovery of excitability to uniform recovery. Moreover, the leading circle hypothesis was evaluated on the ventricular muscle in the present experiment and diameters of the leading circle in the ventricular muscle were determined to be 8∼10 mm.

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In order to study the entrainment phenomenon in various forms of clinical and experimental tachycardia, overdrive pacing was performed in clinical paroxysmal supraventricular tachycardia (PSVT) of Wolff-Parkinson-White syndrome (6 cases), atrial flutter (AF-6 cases), ventricular tachycardia (VT-2 cases), experimental AF induced by Rosenblueh's method (5 dogs), and in VT induced by aconitine (5 dogs). Progressive fusion was demonstrated in all but aconitine-induced VT. After cessation of pacing, the first tachycardia complex showed no fusion at all, but the timing of the complex varied depending on the recording sites of the electrogram. The tachycardia complex occurred at the pacing rate only when the electrogram was recorded at the upstream of the pacing site along the reentry circuit in PSVT and experimental AF. In clinical VT, the complex appeared progressively later as the pacing rate was increased. In aconitine-induced experimental VT, the complex occurred at its original tachycardia rate originating from the site where aconitine was applied. In reentrant tachycardia, entrainment could be observed even when all three of the diagnostic criteria proposed by Brugada et al. were not fulfilled. The mechanism of tachycardia can be assessed by entrainment, although the proposed criteria should be reevaluated.

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Fifteen cases of idiopathic VT responsive to verapamil were studied to examine its clinical, electrocardiographic and electrophysiologic features. All patients were male, aged 15-49, average age 28. Initial onset of VT occurred at ages 9-48 (average 21). Time from onset of VT to first admission was 1-20 years (average 8.2 years), and patients had been followed for 17-40 months (average 27 months). 13 cases had palpitations, 5 had faintness, 1 had syncope, but no deaths were reported. ECG's at time of VT exhibited CRBBB + LAD pattern in 12 cases, CRBBB + RAD pattern in 1, and LBBB in 2. VT rate was 130-200 bpm (average 163 bpm), with QRS width of 0.11-0.16 sec (average 0.14 sec). ECG's during sinus rhythm revealed no ST/T abnormalities, although in 6 cases they were found post-VT. 5 cases had recognizable H waves during VT, and HV intervals were shorter than that during sinus rhythm. VT could be induced by programmed electrical stimulation in 14 cases. VT or RVR could be induced by atrial pacing in 6 of 14, single RV extrastimuli in 12 of 14, paired pulses in 5 of 12, RV overdrive pacing in 7 of 14, and burst pacing in 6 of 14 cases. VT could be terminated by RV burst pacing in 14 of the 15 cases, while single RV stimuli were effective in 5 out of 12 cases. Among the 12 cases in which VT could be induced by single RV extrastimuli, the relationship between changes in premature interval for the induction of VT and the echo interval of VT (extrastimulus to first VT complex) was examined. 8 showed an inverse relationship, 3 showed a concordant relationship and 1 case could not be assessed. An inverse relationship was found between changes in paced cycle length and echo interval for the 2 cases in which VT could be induced by rapid pacing. Verapamil terminated sustained VT in 12 out of 13 cases, and in another case had a pronounced decelerating effect. Prior to termination, VT rate was drastically reduced (from 163 ± 29 bpm to 128 ± 29 bpm). Verapamil was able to prevent the induction of VT in 6 out of 14 cases, while in 6 cases the VT zone was expanded and in 2 cases the VT zone was narrowed. Both minimum and maximum values of premature intervals for induction were significantly extended, from 278 ± 58 sec to 223 ± 82 msec and from 312 ± 93 msec to 629 ± 96 msec, respectively. Reentry was considered as the primary mechanism for verapamil-responsive induced VT among 10 cases examined in this study. However, in 3 cases triggered activity, and in one case enhanced automaticity, was suspected as well. Therefore, no one mechanism can be said to be responsible for this type of VT.

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Employing electrophysiological and pharmacological methods, the mechanisms of recurrent ventricular tachycardia were studied in 31 patients, 18 with old myocardial infarction and 13 with idiopathic ventricular tachycardia. In the cases of ventricular tachycardia with old myocardial infraction, the initiation and termination of the tachycardia could be achieved by programmed electrical stimulation in 13 out of 18 patients. Endocardial mapping showed that the earliest excitation site during tachycardia was at the border zone of infarction, where the diastolic fragmented activity was detected. Programmed electrical stimulation sometimes provoked more than two kinds of QRS morphology of tachycardia in the same patient. Class IA antiarrhythmic agents were effective in terminating tachycardia. These data suggest that there are multiple reentrant pathways consisting of partially depressed fast fibers at the border zone of infarction. In the cases with idiopathic ventricular tachycardia, the induction and termination of tachycardia was effected by electrical stimulation in 8 out of 13 patients. For the termination of tachycardia, long overdrive pacing was sometimes necessary. The diastolic fragmented activity could not be detected by endocardial mapping. A class IV drug such as verapamil was more effective for the termination of tachycardia than class I drugs, and there were repetitive short runs of ventricular extracystole observed until the final termination. These data support the reentrant pathways containing slow with enhanced automaticity as the circuit of idiopathic ventricular tachycardia.

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