Electrophysiologic effects of disopyramide phosphate on reentrant ventricular arrhythmia in conscious dogs after myocardial infarction

The electrophysiologic actions of disopyramide phosphate on reentrant ventricular tachycardia induced by premature ventricular stimuli were evaluated in conscious dogs 2 to 4 days after myocardial infarction. Disopyramide was administered as a series of intravenous infusions to obtain successive steady state plasma disopyramide concentrations of 1.02 ± 0.02, 2.05 ± 0.08, 3.94 ± 0.09 and 7.69 ± 0.18 μg/ml (mean values ± standard error of the mean). Disopyramide plasma concentrations of 1.02 ± 0.02 μg/ml produced an increase in the rate and duration of ventricular tachycardia as well as in the interval during which premature ventricular stimuli produced ventricular tachycardia. The effective refractory period of normal myocardium was decreased and conduction (activation time) was improved in ischemic myocardium. Increasing steady state plasma disopyramide concentrations slowed the rate of ventricular tachycardia without decreasing its duration. Slowing of the rate of tachycardia occurred simultaneously with a depression of conduction in normal and ischemic myocardium and an increase in ventricular refractoriness. Induction of ventricular tachycardia was prevented only at steady state plasma disopyramide concentrations of 7.69 ± 0.18 μg/ml. The results of this study suggest that subtherapeutic plasma concentrations of disopyramide may facilitate the development of reentrant ventricular arrhythmia in the electrically unstable heart. Ventricular tachycardia or fibrillation, or both, may be prevented only by plasma disopyramide concentrations that are in excess of the normal therapeutic range of 2 to 4 μg/ml.     

Reentrant ventricular arrhythmias in the late myocardial infarction period. 9. Electrophysiologic-anatomic correlation of reentrant circuits

We studied isochronal maps of ventricular activation during ventricular arrhythmias induced by programmed premature stimulation in dogs 3-5 days after ligation of the left anterior descending coronary artery. The entire epicardial surface and selective intramural sites were recorded using a computerized multiplexing technique. The electrophysiologic data were correlated with the anatomic characteristics of the infarction. In nine of 17 dogs (55%), the induced ventricular rhythm was due to reentrant activation in the surviving epicardial layer overlying the infarction. The irregular epicardial layer (up to 4 mm thick) had grossly intact myocardial fibers on microscopic examination but showed abnormal electrophysiologic characteristics. The stimulated premature beat that initiated reentry produced a continuous arc of functional conduction block within the surviving epicardial layer. The activation wave front circulated slowly around both ends of the arc of block, rejoined on the distal side of the arc before breaking through the arc to reactivate an area proximal to the block. This resulted in splitting of the initial single arc of block into two arcs. Reentrant activation continued as two synchronous circuits that traveled clockwise around one arc and counterwise around the other. Reentry spontaneously terminated when the leading edge of both reentrant circuits encountered refractory tissue, resulting in the coalescence of the two arcs of block into one. The present study may increase the understanding of the electrophysiologic mechanism of some ventricular repetitive responses and tachyarrhythmias induced by programmed premature stimulation in the clinical laboratory.     

Electrophysiologic studies in survivors of late cardiac arrest after myocardial infarction

Nine patients resuscitated from life-threatening ventricular arrhythmias (VA) within 3 months of an acute myocardial infarction (AMI) underwent electrophysiologic studies (EPS) with clinical follow-up for at least 12 months. Neither reinfarction, drug therapy, nor electrolyte imbalance was a precipitating factor. VA was induced by ventricular pacing in six of nine patients. Five patients were prescribed empiric drug therapy, while the four other patients had repeated EPS to select optimal drug therapy. One patient remained unstable and died of VA in the hospital. No patient was discharged and successfully maintained on a drug known to prevent induction of VA, yet only two patients (25%) had a further recurrence of VA, one fatal. Our findings suggested that either drug therapy that is determined empirically or found not to suppress the induction of VA during EPS can be associated with a successful outcome in some of these patients, or the natural history of VA after myocardial infarction is that they are self-limiting in the absence of a new ischemic event.     

Reentrant ventricular arrhythmias in the late myocardial infarction period: 17. Correlation of activation patterns of sinus and reentrant ventricular tachycardia

The relationship between myocardial sites with late activation during sinus rhythm and sites critical for the initiation and sustentation of reentrant ventricular tachycardia was systematically examined in the 4-day-old postinfarction canine heart. The critical sites for prevention of the initiation of reentry and for termination of sustained figure-of-8 reentrant tachycardia by cryothermal techniques were correlated with the last 20 msec isochrone during sinus rhythm. In 12 experiments, 20 critical sites were examined. The mean distance between sites critical for reentry and the latest isochrone during sinus rhythm was 26.7 +/- 13.3 mm. Only five sites (25%) were within a 12 mm distance, which corresponded to the diameter of the cryoprobe. Nine sites (45%) were within a 24 mm distance (twice the diameter of the cryoprobe), while 11 sites (55%) were separated by more than 24 mm. In three experiments the sites of latest activation during sinus rhythm represented areas showing Wenckebach period or 2:1 conduction block. These sites became dissociated and did not participate in the reentrant excitation induced by premature stimulation. Poor correlation was explained by the fact that sites critical for reentry were intimately related to the location and extent of the arcs of functional conduction block while sites of delayed activation during sinus rhythm were not.     

心肌梗死后室性心律失常的治疗

急性心肌梗死（AMI）和陈旧性心肌梗死（OMI）患者易于伴发各种心律失常，其中室性心律失常（vA）发生率较高，也是导致猝死、危及患者生命的重要因素之一。文献报道AMI后室性早搏（PVB）的发生率为10％-93％，室性心动过速（VT）的发生率为3％-39％，心室颤动（VF）的发生率为4％-36％。每年美国有大约32．5万的人发生心脏猝死（sudden cardiac death，SCD），其中由冠心病引起占80％以上。心肌梗死后发生的VA是猝死最常见的原因，60％AMI性死亡的患者发生在发病后1h内，被认为与VA，     

The relation between ventricular late potential and ventricular arrhythmia in different stages of acute myocardial infarction]

50 cases of acute myocardial infarction (AMI) were examined for ventricular late potential (VLP) six times in total within 4 weeks. At the same time the patients clinical condition was observed. It is found that: (1) In our group the occurrence of VLP in AMI was 28% and VLP was unstable in both acute stage and recovery stage. (2) During acute stage, the difference of positive VLP rate is significant between the ventricular fibrillation group and normal rhythm group (P less than 0.05), but there is no significant difference between the ventricular ectopia group and normal rhythm group. During recovery stage, the difference of positive VLP rate is very significant between the ventricular ectopia and normal rhythm group (P = 0.001). As there was only 1 case of ventricular fibrillation occurring in the recovery stage, no comparison could be made. (3) There is no correlation between VLP and clinical conditions, such as age sex, location of the infarction, existence of old infarction and LVEF. However, the difference of the peak serum CPK level is significant between VLP positive and negative group (P less than 0.05).     

Adrenergic effects on reentrant ventricular rhythms in subacute myocardial infarction.

BACKGROUND. Reentry has been shown to be a mechanism of ventricular arrhythmias elicited by programmed premature stimulation in the subacute ischemic period of dogs subjected to myocardial infarction. The spatial distribution of refractoriness in these hearts has been shown to play an important part in the formation of functional arcs of conduction block during programmed ventricular stimulation. Because the adrenergic nervous system influences cardiac arrhythmias and myocardial infarction can directly affect sympathetic innervation in the heart, we investigated the role of the sympathetic nervous system on reentry in the canine heart 4 days after infarction. METHODS AND RESULTS. The influences of adrenergic stimuli on the initiation of reentrant ventricular excitation were studied using a 128-channel computerized recording system in the canine heart 4 days after ligation of the left anterior descending coronary artery. Bilateral stimulation of the ansae subclavia preferentially improved conduction of premature beats in the normal zones. This corresponded to an improvement in excitability, as measured by a decrease in stimulus strength at the same premature coupling interval as control. Consequently, the effective refractory period was preferentially shortened at normal sites but not at ischemic sites. Both of these changes contributed to a shift of the arc of functional conduction block toward more normal tissue. As a result, sites proximal to the arc of functional conduction block had more time to recover excitability and thereby were available to be reexcited by the distal activation wave front. Conversely, intravenous infusion of norepinephrine preferentially shortened the effective refractory period of sites in the ischemic zone, thereby indicating that denervation hypersensitivity had occurred at these sites. The spatial dispersion of refractoriness and the arc of functional conduction block were significantly reduced in size. As a consequence, previously inducible reentrant rhythms were no longer inducible. CONCLUSIONS. Sympathetic stimulation can be considered an arrhythmogenic intervention, whereas norepinephrine infusion may be considered antiarrhythmic in this experimental model.     

Importance of myocardial infarct artery patency on the prevalence of ventricular arrhythmia and late potentials after thrombolysis in acute myocardial infarction.

Sustained infarct artery patency is an important determinant of survival in patients with acute myocardial infarction. We studied 61 patients with acute myocardial infarction who received intravenous recombinant tissue-type plasminogen activator, aspirin or heparin within 6 hours of symptom onset, to determine if infarct artery patency after intravenous thrombolytic therapy influences myocardial electrical stability as measured by the prevalence of spontaneous ventricular ectopy or late potential activity. Infarct artery patency was determined by angiographic evaluation 2.5 +/- 3 days after infarction. Forty-eight patients (79%) had a patent infarct-related artery and 13 (21%) patients had an occluded vessel. The mean number of ventricular premature complexes (VPCs)/hour (p less than 0.01) and the prevalence of late potentials (54 vs 19%; p less than 0.03) were significantly higher in patients with an occluded versus patent-infarct related vessel. Although VPC frequency and late potentials were not influenced by the time to thrombolytic treatment, patients with a patent infarct-related artery had a lower prevalence of late potentials regardless of whether treatment was initiated less than or equal to 2 hours (25% patent vs 50% occluded; p = not significant) or 2 to 6 hours (16% patent vs 55% occluded; p greater than 0.03) after symptom onset. Thus, successful thrombolysis decreases the frequency of ventricular ectopic activity and late potentials in the early postinfarction phase. The reduction in both markers of electrical instability may help explain why the prognosis after successful thrombolysis is improved after acute myocardial infarction.     

2相折返及折返性室性心律失常

快速性心律失常的发生机制有自律性增高(ａｕｔｏｍａｔｉｃｓｔｒｅｎｇｔｈｅｎ)、触发活动（ｔｒｉｇｇｅｒｅｄａｃｔｉｖｉｔｙ）及折返激动（ｒｅｅｎｔｒｙ） ,其中９０%以上为折返激动所致。折返激动既往均指０相去极化电流所致。本文介绍复极２相折返及折返性室性心律失常。０相折返传统折返概念认为折返的产生及其激动的维持均系由于动作电位０相去极化电流沿折返环路传导所致 ,相毗邻心肌细胞的去极化亦只能由０相电流介导产生 ,即为去极化电流所形成的０相折返。一、折返激动的定义折返激动是指心脏某一激动循一条传导途径传出 …     

Polymorphonuclear leukocyte activity and ventricular arrhythmia in acute myocardial infarction

Polymorphonuclear leukocyte activity was compared with the incidence and severity of ventricular arrhythmia evaluated by Holter electrocardiographic monitoring in 21 patients with acute myocardial infarction. A positive correlation (r = 0.706) was seen between peripheral polymorphonuclear leukocyte count and the amount of leukotriene B4 produced by A23187 (20 microM)-stimulated polymorphonuclear leukocytes on the first hospital day (p less than 0.01). Patients were divided into 3 groups according to the severity of ventricular arrhythmia: no or mild (unifocal, maximal hourly ventricular premature complex rate less than 30, n = 6), moderate (maximal hourly ventricular premature complex rate greater than or equal to 30 or multifocal, n = 6) or severe (R on T, greater than or equal to 2 consecutive ventricular premature complexes or ventricular fibrillation, n = 9). Polymorphonuclear leukocyte count and its leukotriene B4 production were increased with the increase in severity of ventricular arrhythmia among 3 groups. Polymorphonuclear leukocyte count (13,300 +/- 900/microliter, mean +/- standard error of the mean) and its leukotriene B4 production (194 +/- 24 ng/10(7) cells) in patients exhibiting severe ventricular arrhythmia were significantly increased compared with those in patients exhibiting no or mild ventricular arrhythmia (10,300 +/- 1,000/microliter, p less than 0.05 and 120 +/- 21 ng/10(7) cells, p less than 0.05, respectively). Enzymatically estimated infarct size in the latter patient group was significantly smaller than those of the other 2 groups, between which there was no difference in infarct size. These results suggest that polymorphonuclear leukocyte activity is closely related to the incidence and severity of ventricular arrhythmia during the early phase of myocardial infarction.     

Reproducibility of exercise-induced ventricular arrhythmia after myocardial infarction.

To evaluate the reproducibility of exercise-induced ventricular arrhythmia, 155 men with a mean age of 53 +/- 8 years underwent serial exercise testing 3 to 52 weeks after myocardial infarction. The reproducibility of categorical test responses, that is, the presence or absence of ventricular arrhythmia, was evaluated with the kappa coefficient, which considers negative as well as possible test responses and expresses reproducibility above the chance level. Reproducibility was highest at an intertest interval of 1 to 5 days and was not enhanced by further categorizing premature ventricular complexes as simple or complex based on their frequency or configuration. Continuous response measures such as frequency of premature ventricular complexes yielded higher reproducibility than categorical responses. Continuous response measures appear preferable to categorical responses for evaluating the clinical significance and response to antiarrhythmic therapy of ventricular arrhythmias.     

Supraventricular arrhythmias in the late hospital phase of acute Q-wave myocardial infarction. Supraventricular arrhythmia in myocardial infarction

To assess the correlates of supraventricular arrhythmia (SA) in the late hospital phase of acute Q-wave myocardial infarction (MI), continuous 24-h ambulatory electrocardiographic monitoring, gated cardiac pool scan, modified exercise test, and chest x-ray were reviewed in 102 patients. Supraventricular tachyarrhythmias were seen in 11 patients, atrial premature beats in 42 patients; 49 patients did not have SA. Multiple discriminant analysis was used to determine the important variables contributing to the occurrence of SA. Variable included age, sex, history of previous MI, hypertension, location of MI, moist rales at time of admission, cardiothoracic ratio, ejection fraction, wall motion abnormality, exercise test result, duration of exercise and use of digitalis. Moist rales, digitalis, age and cardiothoracic ratio were the predictors of SA. Aging, hemodynamic change imposed on the left ventricle, and arrhythmic effects of digitalis are the major factors associated with SA in the late hospital phase of acute MI.     

Reentrant ventricular arrhythmias in the late myocardial infarction period. 6. Effect of the autonomic system

The effect of the autonomic system on conduction disorders in the infarction zone (IZ) and related reentrant ventricular arrhythmias (RVA) in the late myocardial infarction period in the dog was studied utilizing averaged recordings of the reentrant pathways from the epicardial surface of the IZ. Vagal (V) stimulation was found to have no significant direct electrophysiologic effect while sympathetic (S) stimulation resulted in a direct slight improvement of conduction in the IZ. However, because of the marked rate-dependency of conduction in the IZ, the effects of both V and S stimulation were modified through changes in the heart rate. The bradycardia produced by V stimulation resulted in improvement of conduction in the IZ and disappearance of RVA, while the tachycardia induced by S stimulation resulted in worsening of conduction in the IZ and the occurrence of RVA. Thus, in spite of its slight enhancing effect on conduction in the IZ, the propensity of S stimulation to induce RVA was primarily due to its tachycardiac effect.     

Effect of propranolol in patients with myocardial infarction and ventricular arrhythmia

The Beta-Blocker Heart Attack Trial was a placebo-controlled, randomized, double-blind clinical trial of the long-term administration of propranolol hydrochloride to patients who had had at least one myocardial infarction. Among 3,837 patients followed up for an average of 25 months, 3,290 (85.7%) had 24 hour ambulatory electrocardiograms performed at the baseline examination. Four classifications of arrhythmia were examined. One of these, the presence of complex ventricular arrhythmias (at least 10 ventricular premature beats/h, or at least one pair or run of ventricular premature beats or multiform ventricular premature beats) was the subgroup of major interest. Regardless of the classification, the presence of arrhythmia identifies a group of patients with a higher risk of total mortality, coronary heart disease mortality, sudden cardiac death and instantaneous cardiac death. The a priori subgroup hypothesis that sudden death would be preferentially reduced by propranolol in patients with complex ventricular arrhythmias was not supported. The relative benefit of propranolol in reducing sudden death for this subgroup was 28 versus 16% for the subgroup without ventricular arrhythmia (relative risk of 0.72 versus 0.84, a nonsignificant relative difference of 14%). There were similar findings for two of the three other classifications of arrhythmia and for the other response variables. Although propranolol does not appear to be of special relative benefit in patients with ventricular arrhythmia, the presence of the arrhythmia does identify a high-risk group. The mechanism by which propranolol reduces mortality is still unclear, but is probably not solely an antiarrhythmic one.     

Re-entrant ventricular arrhythmias in the late myocardial infarction period. 5. Mechanism of action of diphenylhydantoin

The mechanism of action of diphenylhydantoin (DPH) on re-entrant ventricular arrhythmias (RVA) was studied in dogs 3-7 days following ligation of the anterior descending coronary artery utilizing direct recordings of the re-entrant pathway (RP) from the epicardial surface of the infarction zone (IZ). DPH in a therapeutic dose consistently prolonged refractoriness of potentially RP in the IZ. This resulted in further impairment and/or block of conduction in the RP and was directly responsible for DPH ability to abolish RVA. On the other hand, DPH had no significant effect on conduction in the adjacent normal zone. Prior to abolition of RVA initiated by premature beats (PBs), DPH resulted in: 1) narrowing of the critical range of coupling intervals of PBs that resulted in re-entry (i.e., the re-entry zone), 2) shift of the narrowed re-entry zone to longer cardiac cycle lengths, and 3) lengthening of the coupling interval of the first re-entrant beat, as well as slowing the rate of re-entrant tachycardia. Thus DPH, similar to lidocaine, owes its antiarrhythmic action in RVS to its selective depressant effect on ischemic cells forming part of the RP.