Method for evaluating the effects of antiarrhythmic drugs on ventricular tachycardias with different electrophysiologic characteristics and different mechanisms in the infarcted canine heart (original) (raw)
Related papers
The American Journal of Cardiology, 1977
The effects of various drugs on delayed activation of the ischemic myocardium and the incidence of ventricular arrhythmias were studied in 34 open-chest anesthetized dogs. The left anterior descending coronary artery was occluded for 6 minutes before and 6 minutes and 42 minutes after administration of aprindine (2.55 mg/kg body weight), quinidine (8 mg/kg) and verapamil (0.2 mg/kg) and during infusion of isoproterenol (0.2 #g/rain). The time intervals from the onset of the QRS complex to the major deflection of the bipolar electrograms recorded within the normal and ischemic zones were measured at cycle lengths of 500, 400 and 300 msec and were correlated with the development of ventricular arrhythmlas. At a cycle length of 500 msec, aprindine increased by 19.5 msec the delay in activation Ume produced by coronary ligaUon alone (P <0.05), whereas verapamii reduced by 10 msec the extent of isohemia-induced conduction delay (P <0.05). The delay in activation time in the ischemic zone was not significantly altered by quinidine or isoproterenol. The incidence of ventricular arrhythmias was increased by aprindine (from 1 in 11 to 8 in 11 dogs), decreased by verapamil (from 3 in 7 to 0 in 7 dogs)and was not changed by quinidineor isoproterenol. Thus, delayed activation of the ischemic myocardium appears to play an important role in the genesis of early arrhythmias due to myocardial ischemia, and drugs that significantly depress conduction in the ischemic myocardium may predispose to the development of ventricular arrhythmia whereas those that improve conduction may be protective. Contrary to their effects on slow channel'dependent conduction, verapamil improved and isoproterenol worsened conduction during ischemia.
Journal of Molecular and Cellular Cardiology, 1984
Studies in cats suggest e-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n = 52), prazosin (1 mg/kg, n = 26), phentolamine (5 mg/kg, n = 18), or phentolamine (same dose) + propranolol (1 mg/kg, n = 10). Alpha-blockade was confirmed by e-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation ofischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO 2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P < 0.01), but not by prazosin or phentolamine + propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachyeardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective ~l-(prazosin), nonselective ~1" and ~2-(phentolamine), and combined ~-and fl-blockade (phentolamine + propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model.
Annals of the New York Academy of Sciences, 1982
Sudden cardiac death has been presumed to be caused primarily by ventricular tachycardia and ventricular fibrillation.1-4 Study of the mechanism of these tachyarrhythmias in man, however, has been limited. The development of intracardiac electrophysiologic techniques for evaluation of ventricular tachyarrhythmias in man and the availability of a large population of survivors of cardiac arrest have now made such studies possible. A more precise understanding of the mechanisms of these tachyarrhythmias may lead to more accurate techniques for predicting vulnerability in individual patients and more specific therapies. The data presented in this report were obtained during electrophysiologic studies performed to define therapeutic regimens in patients who survived out-of-hospital cardiac arrest and were at high risk for recurrence. PATIENT POPULATION AND METHODS Electrophysiologic studies were performed in 59 patients who had been resuscitated from out-of-hospital cardiac arrest. The entry criteria into this study included: (1) the absence of symptoms compatible with acute myocardial infarction or angina at the time of cardiac arrest; (2) absence of evidence of acute myocardial infarction in the immediate post-arrest period; (3) absence of severe hemodynamic impairment (hypotension, low output state, etc.) or immediately life-threatening arrhythmias requiring acute antiarrhythmic therapy during the interval between cardiac arrest and the electrophysiologic study (at least 48 hours) ; (4) the absence of an identifiable and correctable cause of the cardiac arrest (such as drug toxicity or electrolyte disturbance) ; (5) written, informed consent. Acute myocardial infarction was diagnosed by the presence
Circulation Research, 1974
Electrocardiograms and electrograms were recorded in 18 dogs anesthetized with sodium pentobarbital. Using endocardial and epicardial plunge wire electrodes in normal and ischemic or infarcted areas, activation of Purkinje and regular muscle tissue was studied within the first 20-30 minutes and 24 hours after anterior descending coronary artery ligation. The ventricular arrhythmias in the first 20 minutes were abolished during vagally induced atrial arrest, but ventricular automaticity was unchanged from that during the control period. These rate-related arrhythmias were uniformly associated with marked diminution and delay of epicardial activation in the ischemic zone. Slowing of the heart rate caused recovery of the timing, form, and duration of these epicardial potentials with the coincident disappearance of ventricular arrhythmias. The ventricular arrhythmias of the early phase spontaneously subsided with time 20-30 minutes after ligation; concurrently, epicardial activation in the ischemic zone improved. The ventricular arrhythmias noted 24 hours after coronary artery ligation were revealed by vagally induced atrial slowing and suppressed by rapid atrial pacing, indicating the existence of enhanced ventricular automaticity. There was a loss of endocardial muscle activation; Purkinje tissue was depressed but viable in the infarcted zone. The sequence of firing during many of the multifocal ventricular ectopic beats showed that the earliest activation arose from Purkinje tissue in the infarcted zone. However, other ectopic beats appeared to arise from infarcted epicardial muscle.
Journal of The American College of Cardiology, 1987
The purpose of this study was to determine whether alpha-or beta-adrenergic influences directly modulate the rate of spontaneous ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Chloralose-anesthetized, open chest dogs (n = 41) with ventricular tachycardia were studied. The left anterior descending artery was cannulated distally. Neither lntracoronary saline solution nor phenylephrine (0.3 to 12 p,g) changed the rate of ventricular tachycardia; however, isoproterenol (0.01 to 10 p,g) produced dose-dependent increases in the rate. In six dogs, metoprolol, 5 mg given intravenously, slowed ventricular tachycardia from 174 ± 10 (mean ± SE) to 140 ± 17 beats/min (p < 0.05). This was accompanied by decreases in mean arterial pressure from 106 ± 7 to 95 ± 8 mm Hg, cardiac output from 2.6 ± 0.3 to 1.6 ± 0.3 liters/min and prolongation of atrioventricular Recently it has become clear that sympathetic neural influences contribute importantly to the genesis of ventricular tachycardia and fibrillation associated with myocardial ischemia and infarction (1,2). These findings suggest that cardiac denervation (3) or beta-adrenergic blockade (4,5) may be useful in the prevention and treatment of these arrhyth-From the
Journal of Clinical Investigation, 1984
A s bstract. This study was undertaken to investigate the mechanism underlying sustained monomorphic ventricular tachycardia (VT) in late experimental canine myocardial infarction. The hypothesis that sustained and "organized" continuous electrical activity (CEA) displaying a reproducible pattern with recurrent components recorded by bipolar endocardial, intramural, or epicardial electrodes in 10 animals during electrically induced sustained monomorphic VT represented reentrant excitation in an anatomically small area of the ventricle, was evaluated in the light of the following observations: Organized CEA always preceded the first monomorphic ventricular complex (QRS) of VT as well as the discrete local electrograms from closely surrounding sites during the initiation of VT. The site of organized CEA corresponded to the site of origin of sustained VT determined by isochronous contour map analysis of activation sequence. Ventricular pacing at rates more rapid than that of VT failed to terminate VT despite ventricular capture unless it transformed CEA into discrete local electrograms. VT could be terminated in three animals, with a single, critically timed premature stimulus delivered at a critically located focus close to the site of CEA, which would result in local capture and interrupted CEA. In six animals, surgical ablation of the site of organized CEA effectively prevented the reinitiation ofsustained VT by programmed cardiac stimulation. These data showed that organized CEA and sustained VT were closely associated phenomena and suggested that organized CEA probably represented an important component ofthe tachycardia circuit.
Cycle Length Dynamics at the Onset of Postinfarction Ventricular Tachycardias Induced in Canines
Journal of Cardiovascular Electrophysiology, 2000
Tachycardia On.set Dynamics. Introduction: P«.s(infarction monomorphic ventricular tachycurdius induced by projjrainnied .stimulation may display initial cycle length (CL) variations before stabilizing. Methods and Resttlts: To sbow tbat tachycardia onset dynamics depend on rate-dependent electrical properties of the reentrant substrate, we extracted activation times and maximum negative slopes of local activation complexes (-dV/dtn,^,) from 191 unipolar electroj;ranis recorded in the anterior left ventricular wall of anestbetized. 3-day-old infarct canine preparations. Measurements were made of the responses lo programmed stimulation, as well as in early and later beats of tacbycardias, whicb displayed eitbcr a constant trend in CL (group A, n = 5 preparations) or one in wbich CL prolongatitm occurred according t(t an exponential course before stabilizing (group B, n = 9). Stimulation protocols inducing tbe tacbycardias were more aggressive and their CL was significantly shorter (CL = 159 ± 24 msec) in group A than in group B (stabilized CL = 206 ± 34 msec). Reentrant activity occurred in subepicardial areas in whicb the absolute value of-dV/dt^.^(l-dV/dtn,^^ I) was heterogencously depressed (<2 mV/msec). l-dV7dt^.,,l was reduced and activation delay increased in the successive responses to extrastimuli. Further reductions in l-dV/dt^^,) (10*?^ to 23%) were shown to occur between early and later beats in 5 of the 9 tachycardias in group B (no change in the 4 others), and tbey were associated with localized prolongation of conduction times in reentrant pathways. In contrast, |-dV7dt,,,.,^| improved in all group .\ tachycardias (7% to 25%). Conclusion: This study provides evidence that the onset dynamics of postinfarction ventricular tacbycardias are determined by interval-dependent electrical cbanges occurring in the reentrant substrate.