Characterization and incidence of inducible monomorphic ventricular tachycardia in a postinfarction rabbit model

Objective

Ventricular tachycardia (VT), occurring late after myocardial infarction, is an important cause of sudden death. Animal models are useful for the investigation of this arrhythmia. The aim of this study is to develop and characterize a model of late postinfarction monomorphic VT in the rabbit.

Methods and Results

Myocardial infarction was created by ligation of the left circumflex artery. Cardiac electrophysiologic studies were performed 10 to 17 days postinfarction in 39 rabbits, in 10 sham-operated rabbits, and 6 control rabbits. Ventricular tachycardia was defined as a broad-complex tachycardia with a cycle length of more than 100 milliseconds, a duration of more than 10 seconds, and monomorphic QRS complexes. Using programmed stimulation, we induced VT in 9 rabbits (23%) in the infarct group but in none of the sham or control animals. The mean infarct size was 23% ± 9% (mean ± SD) of the left ventricle.

Conclusion

Coronary ligation in the rabbit creates a substrate, which allows the induction of sustained monomorphic VT with programmed stimulation. Monomorphic VT is not inducible in rabbits without myocardial infarction. This model might allow the testing of interventions that reduce the incidence of VT late after myocardial infarction.     

Establishment of a chronic left ventricular aneurysm model in rabbit

Objectives To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm （LVA） in rabbits. Methods Acute myocardial infarction （AMI） was induced in 35 rabbits via concomitant ligation of the left anterior descending （LAD） coronary artery and the circumflex （Cx） branch at the middle portion. Development of AMI was co n-firmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar i n-tra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure （LVESP） and diastolic pressure （LVEDP） were measured before, immediately after and four weeks after ligation. D i-mensions of the ventricular chamber, thickness of the interventricular septum （IVS） and the left ventricular posterior wall （LVPW） left ventricular end diastolic volume （LVEDV） and systolic volume （LVESV）, and ejection fraction （EF） were recorded by echo-cardiography. Results Thirty one （88.6%） rabbits survived myocardial infarction and 26 of them developed aneurysm （83.9%）. The mean area of aneurysm was 33.4% ＆#177; 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the left ventricle （LV） that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. Conclusions Ligation of LAD and Cx at the middle portion could induce develo pment of LVA at a mean area ratio of 33.4%＆#177;2.4%which involves the apex, anterior wall and lateral wall of the LV.     

Arrhythmogenic right ventricular dysplasia: a clinical model for the study of chronic ventricular tachycardia

Arrhythmogenic right ventricular dysplasia (ARVD) is a recently individualised clinical entity which sometimes presents with episodes of ventricular tachycardia (VT). These attacks may be resistant to anti-arrhythmic therapy and new therapeutic approaches have been developed for the treatment of this condition. These new methods are mainly surgical, based on the analysis of the electrical activation of the heart in sinus rhythm and during VT. This approach has increased our understanding of the physiopathology of VT, not only in the context of ARVD, but also in the most commonly encountered clinical setting of VT, after myocardial infarction. Electrophysiological study of the epicardial activation of the dysplastic zones has demonstrated the presence of delayed potentials recorded after the end of the QRS complex. This can be explained by the histopathology of these tissues. ARVD is characterised histologically by partial degeneration of the myocardial wall. Most of the muscle fibers are replaced by fatty tissue in the middle of which some healthy fibers survive. These changes are mainly observed in the intramyocardial and subepicardial layers, the subendocardium being almost normal. Strands of isolated muscle fibers within the non-conducting fatty degeneration may lead to very delayed activation with respect to the adjacent healthy tissues. The propagation of activation is delayed as it passes through this plexiform structure and in the zones adjacent to healthy muscle were reentry phenomena may arise. In ARVD, these changes are mainly located over the right ventricle, so explaining the right ventricular origin of most forms of VT observed in this condition. However, we have also observed a case which suggested an isolated arrhythmogenic left ventricular dysplasia. Epicardial mapping localizes the point of origin of VT in zones situated between the slow and normally conducting tissues. Simple ventriculotomy, a full thickness section of the ventricular wall, at the point of epicardial breakthrough of the VT prevents recurrence in the great majority of patients. The same pathophysiological concepts may be applied to VT complicating myocardial infarction but in this situation the myocardial fibers capable of slowly conducting the activation are isolated within the fibrous tissue in the border zone of the infarct. The point of origin of VT is usually within the interventricular septum with a point of epicardial breakthrough which could be located some distance away. Different surgical techniques have been developed to deal with this condition. Encircling endocardial ventriculotomy isolates the arrhythmogenic zone from the rest of healthy tissues by tracin     

Catheter ablation of ventricular tachycardia by intramyocardial injection of ethanol in an animal model of chronic myocardial infarction

INTRODUCTION: Direct injection of ethanol into myocardium has been shown to create large, well-demarcated lesions with transmural necrosis in normal ventricular myocardium and in regions of healed myocardial infarction. The aim of this study was to investigate the effects of direct ethanol injection on the inducibility of ventricular tachycardia (VT) in an animal model of chronic myocardial infarction. METHODS AND RESULTS: Eight sheep with reproducibly inducible VT underwent an electrophysiologic study 139 +/- 65 days after myocardial infarction. Noncontact mapping was used to analyze induced VT. Fifteen different VTs were targeted for catheter ablation. Ablation was achieved by catheter-based intramyocardial injection of a mixture of 96% ethanol, glycerine, and iopromide (ratio 3:1:1). Direct intramyocardial ethanol injection resulted in noninducibility of any VT 20 minutes after ablation in 7 of 8 animals. Four of 5 animals with initially successful ablation remained noninducible for any VT at follow-up study at least 2 days after the ablation procedure. Microscopic examination revealed homogeneous lesions with interstitial edema, intramural hemorrhage, and myofibrillar degeneration at the lesion border. The lesions were well demarcated from the surrounding tissue by a border zone of neutrophilic infiltration. CONCLUSION: Catheter ablation of VT by direct intramyocardial injection of ethanol during the chronic phase of myocardial infarction is feasible. It may be a useful tool for catheter ablation when the area of interest is located deep intramyocardially or subepicardially or when a more regional approach requires ablation of larger amounts of tissue.     

Emergency treatment of chronic ventricular tachycardia after myocardial infarction by endocavitary fulguration

Endocavitary catheter ablation consists of delivering an impulse of 160 to 240 joules via a catheter used for electrophysiological investigation resulting in an electrical discharge which, in addition to its thermal effects may alter the arrhythmogenic substrate mechanically. This method was used in 2 patients with resistant and recurrent VT after myocardial infarction complicated by ventricular aneurysm. Two sessions of catheter ablation were necessary in both patients, but in the second one a single shock was successful in critically ill patients with VT. The first patient has been followed up for 20 months and the second for 13 months. Under prophylactic antiarrhythmic therapy, neither patient has had recurrence of the ventricular arrhythmias which had previously led to their hospitalisation. Catheter ablation is therefore presented as a technique which may be performed in the electro-physiological laboratory and repeated in cases of incomplete efficacy. This method may be used successfully in the treatment of chronic VT after myocardial infarction complicated by ventricular aneurysm.     

Arrhythmia inducibility and ventricular vulnerability in a chronic feline infarction model

Ventricular tachyarrhythmias are the cause of sudden cardiac death in ischemic heart disease. Reliable animal models are necessary to study techniques for identifying individuals at risk and to develop effective modes of therapy. The purpose of the present study was to evaluate the inducibility of ventricular tachyarrhythmias and vulnerability to ventricular fibrillation and to correlate these findings with changes in ventricular refractoriness in a chronic feline model. Twelve conditioned cats were randomly divided into two groups: group A, sham-operated controls (n = 5); or group B, permanent occlusion of the left anterior descending coronary artery (n = 7). Two weeks later, the following measurements were made: (1) assessment of refractory periods at several ventricular sites; (2) inducibility to ventricular tachyarrhythmias; and (3) determination of ventricular fibrillation threshold. After electrophysiologic testing, the animals were killed and the hearts were studied histologically. Ventricular fibrillation thresholds were significantly lower in group B compared with group A (13 +/- 3 vs 46 +/- 9 mA; p less than 0.01). One of the sham-operated controls had induction of nonsustained ventricular tachycardia, while six of the group B animals had reproducible, inducible ventricular tachyarrhythmias (p less than 0.01). There was a significant dispersion in effective refractory periods between normal and infarcted sites in group B (46 +/- 6 msec) not seen in group A (12 +/- 2 msec, p less than 0.01). The group A cats demonstrated minimal damage to the myocardium or cardiac architecture. Group B cats demonstrated extensive, transmural, homogeneous infarcts of approximately 30% of the anterior wall of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Polymorphous ventricular tachycardia in acute myocardial infarction

Polymorphous ventricular tachycardia (VT) is thought to be uncommon in acute coronary heart disease, but its prevalence has not been determined. Seven hundred seventy-one consecutive patients admitted with acute myocardial infarction (MI) were reviewed for the occurrence of this arrhythmia. Nine patients (1.2%) had polymorphous VT. No patient had any of the predisposing factors previously associated with polymorphous VT. The arrhythmia was resistant to multiple drugs, and repeated cardioversion was effective in only 3 patients. Overdrive pacing was ineffective in the 3 patients in whom it was attempted. Verapamil was effective in 3 of 4 patients in whom it was tried. Six patients with polymorphous VT died during hospitalization; the remaining 3 died within 6 months of discharge. It is concluded that, when compared with regular VT, polymorphous VT in MI carries a poor prognosis. When the arrhythmia occurs in the context of acute ischemia, it appears to be more difficult to treat compared with its occurrence due to other predisposing factors. Verapamil, not usually indicated for ventricular arrhythmias, should be tested in a therapeutic trial.     

Nature of inducible ventricular tachyarrhythmias in a canine chronic myocardial infarction model

A canine model suitable for serial conscious studies was developed to evaluate the nature of sustained ventricular tachyarrhythmias in chronic experimental myocardial infarction. Thirteen dogs underwent left anterior descending coronary artery ligation followed by complete reperfusion; 11 sham-operated dogs served as controls. In this model, ventricular tachyarrhythmias are inducible in most dogs with experimental infarction and in several dogs without this condition. The morphologic features, rate and drug response of the induced arrhythmias are unlike those of human ventricular tachycardia. Tachyarrhythmia induction is facilitated by anesthesia and thoracotomy. This canine infarct model does not adequately imitate human recurrent ventricular tachycardia, but may simulate human sudden cardiac death.     

Anisotropy and reentrant ventricular tachycardia: experimental model in the isolated rabbit heart

The purpose of this study was to study the role of anisotropic distribution of conduction velocity in the initiation and perpetuation of ventricular tachycardia in an experimental model of sustained reentrant ventricular tachycardia in the Langendorff perfused rabbit heart. The hearts of 30 rabbits were used in the study. The right ventricle, the interventricular septum and the endocardial and intramural layers of the left ventricle were destroyed by freezing. In the surviving epicardial layer an obstacle was created using a cryoprobe. Thus, the final preparation consisted of a perfused ring of epicardium in the left ventricle. In 27 of 30 experiments programmed electrical stimulation induced sustained reentrant excitation around the obstacle. The cycle length of the tachycardia ranged from 128 to 197 ms in different experiments (mean 162 +/- 17 ms). During tachycardia in some segments of the ring the impulse propagated parallel to fiber orientation at a mean conduction velocity of 61 +/- 7 cm/s whereas in other segments of the ring the impulse propagated perpendicular to fiber orientation at a mean conduction velocity of 22 +/- 4 cm/s. An excitable gap was present during all episodes of tachycardia. In conclusion, conduction velocity during reentrant tachycardia depends on the relation between direction of propagation and fiber orientation. This anisotropic distribution of conduction velocity can play an important role in the initiation and perpetuation of ventricular tachycardia.     

Valsalva termination of ventricular tachycardia in myocardial infarction

A 66-yr-old patient with recurrent monomorphic ventricular tachycardias subsequent to a previous myocardial infarction is reported. The tachycardia could repeatedly be terminated by the Valsalva manoeuvre. Procainamide, infused shortly before, possibly had an additional effect. As far as we know, this is the first report of ventricular tachycardias, as a result of an old myocardial infarction, that could be terminated by the Valsalva manoeuvre.     

Mapping of epicardial activation in a rabbit model of chronic myocardial infarction:

Introduction: This study examines the consequences of a large transmural apical infarct on the epicardial electrical activity in isolated rabbit hearts.
Methods and Results: Hearts were isolated 8 weeks after coronary artery ligation. Membrane voltage from the epicardial surface of the left ventricle (LV) including the infarct was monitored using the voltage sensitive dye RH237. Optical action potentials were detected from the epicardial surface of the infarct; the signal amplitude was ∼20% of those in the noninfarcted zone (NZ). Epicardial activation mapping of the LV free wall showed that during right atrial (RA) pacing, the activation sequence was not significantly different between infarcted and sham-operated groups. However, direct stimulation of the epicardium in the NZ revealed an area of slow conduction velocity (CV ∼5 cm/s⁻¹, ∼10% of normal values) at the margin of the infarct zone (IZ). Within the IZ, CV was ∼50% of normal. A prominent endocardial rim of myocardium in the infarct was not the source of epicardial optical signals because chemical ablation of the endocardium did not affect the epicardial activation pattern.
Concluson: Therefore, remnant groups of myocytes in the mid-wall and epicardium of the infarct scar support normal electrical activation during RA pacing. Areas of delayed conduction emerge only on epicardial stimulation.     

Identification of reproducible ventricular tachycardia in a canine model

Epicardial mapping was used as a standard to investigate how well the limb leads, both alone and in conjunction with 5 select epicardial electrodes, can verify reproducibility in a common, open-chest canine model of ventricular tachycardia (VT). Reproducible VT was defined as 2 or more episodes of monomorphic VT with similar rates, limb lead tracings and epicardial maps. In this study, 21 dogs underwent 2-hour occlusion of the left anterior descending coronary artery followed by reperfusion. Three days later, programmed stimulation was used to induce VT that was analyzed with limb leads I, II and III and 27 simultaneously recorded, bipolar epicardial electrodes. Thirteen dogs had VT of which 11 had polymorphic VT (varying QRS morphology). Twelve dogs yielded at least 1 form of monomorphic VT. Eight had 2 or more distinct forms of monomorphic VT (pleomorphism). Four of these 8 dogs had pleomorphic VT that was not apparent from the limb lead tracings, but was recognized from the epicardial activation maps constructed from the 27 epicardial recordings. To provide a method of distinguishing various VTs without the need of full epicardial mapping, 5 of the 27 epicardial electrodes were selected. These were positioned over the midanterior and midposterior right and left ventricles, and the left ventricular apex. By analyzing electrogram morphology and activation time, VT reproducibility could be as accurately identified with these 5 electrodes as with epicardial mapping derived from 27 electrodes. In conclusion, multiple VT morphologies are common in this open-chest canine model. Limb lead recordings alone are inadequate for analysis of VT reproducibility.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dispersion of the monophasic action potential duration in patients with polymorphic ventricular tachycardia.

The mechanism of polymorphic ventricular tachycardia (PMVT) remains unclear. To investigate the electrophysiologic mechanism of PMVT, monophasic action potentials (MAPs) were recorded with a contact electrode technique from right ventricular sites during sinus rhythm and right ventricular pacing. MAPs were obtained from 6 patients with PMVT (PMVT group) and 11 patients without PMVT (control group). The duration from the onset of the upstroke to 90% repolarization of the MAP (MAPD90) during right ventricular pacing at both pacing cycle lengths of 600 and 400 ms was significantly longer in the PMVT group than in the control group (332+/-60 ms vs 279+/-33 ms [P < .005] and 276+/-32 ms vs 229+/-23 ms [P < .0001], respectively). Dispersion of the MAPD90 in sinus rhythm was significantly larger in the PMVT group than in the control group (52.5+/-34.6 ms vs 26.1+/-12.0 ms [P < .005]), and dispersion of the MAPD90 during right ventricular pacing at both pacing cycle lengths of 600 and 400 ms was also significantly larger in the PMVT group than in the control group (86.0+/-44.2 ms vs 37.4+/-28.6 ms [P < .005], and 48.8+/-19.3 ms vs 27.1+/-7.1 ms [P < .05], respectively). Dispersion of repolarization time (activation time plus MAPD90) at a pacing cycle length of 600 ms was longer in the PMVT group than in the control group (104.3+/-38.9 ms vs 49.4+/-31.2 ms [P < .05]). These results suggest that the patients with PMVT have a greater regional dispersion of ventricular repolarization time and that the heterogeneity of ventricular repolarization may play an important role in the genesis of PMVT.     

Recurrence of ventricular tachycardia degeneration by low-energy implantable cardioverter-defibrillator shocks: a case report

Despite their proven efficacy at reducing mortality in selected patients, implantable cardioverter-defibrillators have some proarrhythmic effects. In this report, we present a case of a patient with recurrent ventricular tachycardia degeneration to ventricular fibrillation by appropriate low-energy implantable cardioverter-defibrillator shocks.     

Type II bidirectional ventricular tachycardia in a patient with myocardial infarction

A 84-year-old man presented to the emergency department complaining of chest pain and palpitations. He had no history of coronary artery disease. The 12-lead electrocardiography showed bidirectional ventricular tachycardia (BVT). Coronary angiography revealed severe mid left anterior descending and mid left circumflex lesions. The BVT, in this case, was most likely due to myocardial ischema. The ethiology of published BVT cases are most commonly digitalis toxicity and rarely herbal aconitine poisoning, hypokalemic periodic paralysis, cathecolaminergic VT, myocarditis, and Anderson-Tawil syndrome. The patient had neither of these underlying conditions. To the best of our knowledge and research in the literature, there was no report of bidirectional VT in the patients with myocardial infarction.     

The role of ventricular tachycardia ablation in the reduction of implantable defibrillator shocks

Frequent shocks from an implantable defibrillator (ICD) can have adverse cardiac affects and lead to increased pain, anxiety, and a decreased quality of life. Pharmacologic attempts and ICD reprogramming strategies aimed at reducing ICD shocks have modest results, with frequent discontinuation of medicines because of side effects. Ventricular tachycardia (VT) ablation is recommended in the treatment of patients with frequent ICD shocks caused by VT. VT ablation may also be considered in patients with an initial ICD shock and as prophylactic treatment in patients with a history of sustained VT who are undergoing ICD implant.