Standardized programming to reduce the burden of inappropriate therapies in implantable cardioverter defibrillators - Single centre follow up results.

BACKGROUND: Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful. AIM: Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS. METHOD: A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming. RESULTS: 39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies. CONCLUSIONS: The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation.

Advances in the treatment of atrial fibrillation.

Management of atrial fibrillation (AF) has changed greatly in the past 10 years. The advent of a greater understanding of the pathophysiology of AF has resulted in major therapeutic breakthroughs, both in invasive and non-invasive strategies. New antiarrhythmic agents with fewer side effects, new anticoagulants and technical advances in ablation have changed the treatment of this condition. Molecular modification of the highly effective amiodarone, to improve safety and tolerability, has produced promising analogues such as Dronedarone. Although this drug seems less effective than amiodarone in preventing AF recurrence, the drug presented an interesting data on reduction of stroke and cardiovascular death, a novel effect that needs further investigation. New antiarrhythmics with atria selectiveness such Vernakalant, might be useful for cardioversion in AF without ventricular proarrhythmia. Dabigatran, a prodrug that directly inhibits thrombin, represents an alternative to warfarin for anticoagulant treatment in selected patients. In AF ablation, technological advances are sure to result in the necessary improvements in the safety and procedures efficacy. These technologies include ablation catheters designed to electrically isolate the pulmonary veins with improved safety, efficacy, speed, and precision and improved imaging and electrical mapping systems. Although pulmonary vein isolation remains essential for most ablation procedures, the role of substrate modification has taken on increasing importance. In this article, we review the advances in the treatment of AF, focus on the new medications and advances in invasive procedures.

Clinical assessment of clonidine in the treatment of new-onset rapid atrial fibrillation: a prospective, randomized clinical trial.

PURPOSE: The role of digoxin and verapamil in the control of ventricular response in rapid atrial fibrillation is well established. This study investigates how clonidine compares with these standard therapies in rate control for new-onset rapid atrial fibrillation. We set out to test the hypothesis that clonidine effectively reduces heart rate in patients with new-onset rapid atrial fibrillation. SUBJECTS AND METHODS: Forty patients were seen in the emergency department with new-onset (< or =24 hours' duration), stable, rapid atrial fibrillation. Eligible patients were randomized to receive either clonidine, digoxin, or verapamil. Changes in heart rate and blood pressure over 6 hours, as well as frequency of conversion to sinus rhythm were recorded and analyzed. RESULTS: The mean reduction in heart rate over 6 hours was 44.4 beats/min (95% confidence interval [CI] 28.4-60.4 beats/min) in the clonidine group, 52.1 beats/min (95% CI 40.8-63.4 beats/min) in the digoxin group, and 41.8 beats/min (95% CI 22.5-61.0 beats/min) in the verapamil group. Analysis of variance of the heart rate changes in the 3 groups after 6 hours was not significant (P =.55). At 6 hours, 7 of 12 clonidine patients, 8 of 15 digoxin patients, and 7 of 13 verapamil patients remained in atrial fibrillation (P =.962 on chi(2)). CONCLUSION: Clonidine controls ventricular rate in new-onset atrial fibrillation with an efficacy comparable to that of standard agents.

Relationship between pacemaker dependency and the effect of pacing mode on cardiovascular outcomes.

BACKGROUND: A recently completed trial, the Canadian Trial of Physiological Pacing (CTOPP), showed that physiological pacing did not significantly reduce mortality, stroke, or heart failure hospitalization, but it did show that atrial fibrillation occurred less frequently in patients with physiological pacing. Many pacemaker patients experience only transient bradyarrhythmias with an adequate unpaced heart rate (UHR) and are not pacemaker-dependent. The purpose of the present analysis was to determine if pacemaker-dependent patients have an increased benefit from physiological pacing compared with non-pacemaker-dependent patients. METHODS AND RESULTS: Of 2568 patients included in the CTOPP trial, 2244 patients had a pacemaker dependency test performed at the first follow-up visit. The yearly event rate of cardiovascular death or stroke steadily increased with decreasing UHR in the ventricular pacing group, but it remained constant in the physiological pacing group. When the patients were subdivided to UHR 60 bpm, there was an interaction between pacing mode treatment and UHR subgroup. The Kaplan-Meier plot confirmed a physiological pacing advantage only in the UHR

Circadian variation of paroxysmal atrial fibrillation. PA3 Investigators. Atrial Pacing Peri-ablation for Prevention of Atrial Fibrillation Trial.

The circadian variation of paroxysmal atrial fibrillation (AF) was studied in 67 patients who received a dual-chamber pacemaker 3 months before a planned atrioventricular node ablation. A distinct circadian variation of AF was observed with 2 time peaks in initiation (1 in the early morning and 1 in the early evening hours), which was modulated by atrial pacing, the duration of AF, and the use of beta-adrenergic blocking agents.

Dysautonomia among patients with fibromyalgia: a noninvasive assessment.

OBJECTIVE: Fibromyalgia (FM) is a prevalent and poorly understood disorder associated with a significant amount of disability. Some clinical characteristics are common to both FM and vasovagal syncope (which is caused by dysautonomia). We assessed the response of patients with FM to a head up tilt table test (HUT). We also examined sympathovagal balance by assessing heart rate variability (HRV). METHODS: We studied 17 women with FM and 14 female control subjects. After baseline functional assessments, they underwent a 3 stage HUT (with isoproterenol). HRV was assessed over a 24 h period and also before and during HUT. Quality of life was assessed using the Medical Outcomes Study SF-36 Short Form Health Survey. RESULTS: HUT was positive in 64.7% of the patients with FM compared with 21.3% of controls (p = 0.016). FM patients had less HRV, as measured by either time domain or frequency domain analysis. The FM group had a different response to HUT than controls. Quality of life was significantly lower in patients with FM compared to controls (p < or = 0.001 in all domains). CONCLUSION: Patients with FM have abnormal responses to 2 tests of autonomic nervous system function. Further research is needed to determine if dysautonomia plays a role in the pathogenesis of FM or is a result of FM.

Ventilatory assistance improves exercise endurance in stable congestive heart failure.

We postulated that ventilatory assistance during exercise would improve cardiopulmonary function, relieve exertional symptoms, and increase exercise endurance (T(lim)) in patients with chronic congestive heart failure (CHF). After baseline pulmonary function tests, 12 stable patients with advanced CHF (ejection fraction, 24 +/- 3% [mean +/- SEM]) performed constant-load exercise tests at approximately 60% of their predicted maximal oxygen consumption (V O(2)max) while breathing each of control (1 cm H(2)O), continuous positive airway pressure optimized to the maximal tolerable level (CPAP = 4.8 +/- 0.2 cm H(2)O) or inspiratory pressure support (PS = 4.8 +/- 0.2 cm H(2)O), in randomized order. Measurements during exercise included cardioventilatory responses, esophageal pressure (Pes), and Borg ratings of dyspnea and leg discomfort (LD). At a standardized time near end-exercise, PS and CPAP reduced the work of breathing per minute by 39 +/- 8 and 25 +/- 4%, respectively (p < 0. 01). In response to PS: T(lim) increased by 2.8 +/- 0.8 min or 43 +/- 14% (p < 0.01); slopes of LD-time, V O(2)-time, V CO(2)-time, and tidal Pes-time decreased by 24 +/- 10, 20 +/- 11, 28 +/- 8, and 44 +/- 9%, respectively (p < 0.05); dyspnea and other cardioventilatory parameters did not change. CPAP did not significantly alter measured exercise responses. The increase in T(lim) was explained primarily by the decrease in LD- time slopes (r = -0.71, p < 0.001) which, in turn, correlated with the reductions in V O(2)-time (r = 0.61, p < 0.01) and tidal Pes-time (r = 0.52, p < 0.01). in conclusion, ventilatory muscle unloading with PS reduced exertional leg discomfort and increased exercise endurance in patients with stable advanced CHF.

Correlation of waiting time with adverse events in patients admitted for nonelective permanent pacemaker implantation.

OBJECTIVE: To determine the effect of a dedicated permanent pacemaker implantation procedure room on waiting time and waiting time-related morbidity. DESIGN: Retrospective chart review. SETTING: Two tertiary care teaching hospitals in southern Ontario; one with a dedicated procedure room (centre B) and one without (centre A). PATIENTS: Two hundred and fourteen consecutive patients who required permanent pacing urgently or emergently. METHODS: Charts were examined retrospectively at centre A (131 patients) and centre B (83 patients) to determine the waiting time for and the number of preoperative adverse events in nonelective permanent pacemaker implantation. RESULTS: Patients in centre A waited a mean of 4.5 +/- 3.0 days while patients in centre B waited a mean of 1.9 +/- 1.6 days (P = 0.0001). Centre A patients experienced a total of 57 adverse events that were likely or possibly related to the waiting period, while patients at centre B experienced eight such events (P < 0.0001). Thirty-three per cent of the centre A patients experienced at least one adverse event, while 8% of centre B patients experienced at least one adverse event (P < 0.00001). Of the centre A patients who waited for more than six days (26 patients), 58% had at least one adverse event, compared with 26% of those who waited less than six days (105 patients, P = 0.0009). CONCLUSIONS: Delays in implanting nonelective permanent pacemakers are strongly associated with an increase in adverse events. Measures to shorten the waiting time are likely to result in a reduction in morbidity in conjunction with a beneficial impact on health care resource utilization.

Recognition of electrocardiographic left arm/left leg lead reversal.

The electrocardiographic error of left arm/left leg lead reversal is difficult to identify. PI amplitude greater than PII as a terminal positive component to PIII may diagnose 90% of such errors.

Is there a sex bias in the selection of permanent pacemaker implantations?

OBJECTIVE: To determine whether there is a sex bias in a historical cohort of consecutive patients who underwent initial pacemaker implantation at a Canadian teaching hospital by determining whether women were less likely to receive physiological pacemakers. DESIGN: Retrospective chart review. SETTING: A Canadian, tertiary care teaching hospital. PATIENTS: A total of 446 patients (192 female) had a first-time pacemaker implantation between January 1, 1990 and September 30, 1993 at Kingston General Hospital, Kingston, Ontario. RESULTS: Physiological pacemakers (dual chamber or atrial only) were implanted in 125 male patients (49.2%) and in 93 female patients (48.4%), for an absolute difference of 0.8%. In patients deemed eligible for physiological pacemaker implantation (absence of absolute or relative contraindications to physiological pacing), 63.8% of male patients and 60.6% of female patients received physiological pacemakers. Pacemakers with rate-modulation were implanted in 109 male patients (42.9%) and in 80 female patients (41.7%). These differences were not significant. CONCLUSION: No sex difference in the selection of physiological or rate-modulated permanent pacemakers was demonstrated in this study.

Effects of heptanol, class Ic, and class III drugs on reentrant ventricular tachycardia. Importance of the excitable gap for the inducibility of double-wave reentry.

BACKGROUND: Double-wave reentry (DWR) can be a mechanism for acceleration of ventricular tachycardia (VT) with a large excitable gap (EG). The purpose of this study was to determine the effects of heptanol, class Ic, and class III drugs on the inducibility of DWR. METHODS AND RESULTS: In 11 Langendorff-perfused rabbit hearts, a thin ring of anisotropic left ventricular epicardium was created by a cryoprocedure. VT with a revolution time of 180 +/- 26 milliseconds and an EG of 106 +/- 8 milliseconds was induced by incremental pacing. During control, entrainment with 10 stimuli at a 99 +/- 15-millisecond interval terminated VT in seven hearts. In four hearts VT was accelerated from 205 +/- 24 to 115 +/- 14 milliseconds by introduction of a second circulating wave in the ring. In the seven VTs that could not be accelerated, 0.5 mumol/L Org7797 (class Ic) and 1.0 mmol/L heptanol (uncoupling agent) prolonged the cycle length of VT by 32% and 37%, respectively. Because the refractory period (RP) only increased by 11%, the EG prolonged by 71% and the ratio between EG and RP was increased from 0.66 to 1.00. Under these conditions, DWR could be induced in all seven hearts. In the four VTs that could be accelerated during control, administration of the class III drug D-sotalol (35 mumol/L) only slightly slowed VT by 6%. Because the RP was prolonged by 15%, the ratio between the EG and the RP decreased from 0.76 to 0.63. Entrainment now failed to accelerate VT in two of four hearts, whereas in the two other hearts, double-wave reentry self-terminated within eight cycles. CONCLUSIONS: Drugs that increase the ratio of EG and RP enhance the susceptibility to acceleration of VT, whereas drugs that decrease this ratio prevent induction of sustained double-wave reentry.

Ambulatory esophageal manometry, pH-metry, and Holter ECG monitoring in patients with atypical chest pain.

Standard Holter electrocardiographic (ECG) monitoring was combined with ambulatory esophageal manometry and pH-metry in 25 patients with atypical chest pain in order to determine whether an association could be found between spontaneous pain episodes and ischemic ECG changes or esophageal dysfunction. Results of ambulatory testing were compared to those obtained with standard esophageal manometry and provocative testing. Twenty-two of the 25 patients experienced a total of 88 pain episodes during ambulatory testing. Although 15 of the 22 patients (68%) experiencing pain during testing had at least one pain episode that correlated temporally with gastroesophageal reflux, esophageal dysmotility or ischemic ECG changes, 65% of all pain episodes were unrelated to abnormal esophageal events or ECG changes. Seventeen percent of pain episodes were associated with gastroesophageal reflux, 15% with esophageal dysmotility, and 2% with a combined acid reflux and esophageal dysmotility event. Only one pain episode was associated with ischemic ECG changes. Twelve of the 15 patients with chest pain episodes associated with reflux or esophageal dysmotility had other identical pain episodes in which there was no correlation. Reproduction of a patient's pain during standard manometry with provocative testing did not predict a strong correlation between the patient's spontaneous pain episodes and esophageal dysfunction during ambulatory recordings. In summary, patients with atypical chest pain have relatively few spontaneous pain episodes that correlate with gastroesophageal reflux, esophageal dysmotility, or ischemic ECG changes. It appears that different stimuli can trigger identical episodes of chest pain, which suggests that many of these patients may have dysfunction of their visceral pain sensory mechanisms.

Plasma disposition and hemodynamic effects of a single oral dose of isosorbide dinitrate in human males and females.

The goal of the present work was to determine the plasma disposition and hemodynamic effects of isosorbide dinitrate (ISDN) in human males and females. Fourteen healthy human volunteers took part in the study; seven males, 21.7 +/- 2.5 y (SD), and seven females, 20.7 +/- 3.4 y. Measurements of forearm blood flow (FBF), vascular conductance (FVC), and venous capacitance (Cv) were obtained by venous occlusion plethysmography, whereas blood pressure was measured by automatic sphygmomanometry. Blood samples were taken through a catheter placed in the antecubital vein at 0, 15, 30, 45, 60, 90, 120, 360, 480, 720, and 1440 min following a single 10 mg oral dose of ISDN. Plasma concentrations of ISDN and its mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN), were determined by large bore capillary column gas-liquid chromatography. Hemodynamic measurements were made at corresponding experimental times up to 480 min. No differences were observed in the disposition of ISDN, 2-ISMN or 5-ISMN between the male and female volunteers. In addition, the plasma concentrations of ISDN and its mononitrate metabolites did not consistently correlate with the hemodynamic changes of the individual subjects. Diastolic blood pressure was significantly decreased for a 0.5 h period starting at 30 min, which was the time at which plasma ISDN concentrations peaked, and which preceded the time when the plasma concentrations of 2-ISMN and 5-ISMN were maximal. These observations indicate that, for a single 10 mg oral dose of ISDN, there were no gender-dependent differences in the plasma disposition of the parent drug or its mononitrate metabolites, and the vascular changes responsible for the decrease in diastolic blood pressure in these volunteers occurred in vascular beds other than those of skeletal muscle as represented by forearm blood flow.

Echo-wave termination of ventricular tachycardia. A common mechanism of termination of reentrant arrhythmias by various pharmacological interventions.

BACKGROUND: Based on epicardial mapping, different mechanisms of termination of reentrant ventricular tachycardia by various pharmacological interventions are described. METHODS AND RESULTS: In 40 Langendorff-perfused rabbit hearts, rings of anisotropic left ventricular epicardium were made by a cryoprocedure. Sustained monomorphic ventricular tachycardia based on continuous circus movement of the impulse around the ring was induced by programmed stimulation. Increasing doses of heptanol (n = 10), potassium (n = 10), tetrodotoxin (n = 6), RP62719 (a new class III drug) (n = 4), flecainide (n = 5), and propafenone (n = 5) were administered to terminate ventricular tachycardia. Epicardial mapping (248 points) was used to study the mechanism of termination of ventricular tachycardia. In 28 of 40 hearts, ventricular tachycardia terminated because the drugs produced complete conduction block of the impulse in a segment of the reentrant pathway. In the remaining 12 hearts (heptanol, n = 2; potassium, n = 3; tetrodotoxin, n = 2; RP62719, n = 2; flecainide, n = 1; and propafenone, n = 2), termination of ventricular tachycardia occurred by collision of the circulating impulse with a spontaneous antidromic wave front reflected within the circuit. This phenomenon occurred when the circulating impulse encountered an arc of functional conduction block that did not extend along the whole width of the ring. As a result, the impulse dissociated into a continuing orthodromic circulating wave and a returning antidromic echo-wave caused by microreentry within the ring. CONCLUSIONS: Independent of their mechanisms of action, sodium channel blockers, electrical uncouplers, and class III drugs terminate reentrant ventricular tachycardia either by complete conduction block or by collision of the impulse with an echo-wave.

Sustained monomorphic ventricular tachycardia: a single electrocardiographic expression of different patterns of reentry.

UNLABELLED: Sustained monomorphic ventricular tachycardia (SMVT) can be the electrocardiographic expression of a reentrant impulse in the ventricles. In this study we analyzed the different types of reentry that might lead to SMVT. METHODS: The pattern of activation of 73 episodes of SMVT induced in thin sheets of epicardium in 50 Langendorff perfused rabbit hearts were visualized with high resolution epicardial mapping (248 points). RESULTS: Five different patterns of reentry resulting in SMVT were identified: (1) Single-loop reentry around a fixed obstacle (n = 40); (2) Single-loop reentry around a functional arc of conduction block (n = 17); (3) Double-wave reentry around a fixed obstacle (n = 9); (4) Figure-of-eight reentry around two areas of functional block (n = 5); and (5) Multiple synchronized circuits around multiple areas of functional block (n = 2). CONCLUSION: SMVT is a single electrocardiographic expression of different patterns of reentry. Accurate mapping is mandatory to identify the reentrant pathway and the pathophysiological substrate of the arrhythmia.

Relationship between myocardial amiodarone concentration and antiarrhythmic effect in dogs with myocardial infarction and electrically induced ventricular arrhythmias.

The relationship between the antiarrhythmic effect of amiodarone and its myocardial concentration was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia or ventricular fibrillation. Three groups of animals (n = 10/group) received amiodarone, 40 mg.kg-1.day-1 (low-dose amiodarone), amiodarone 60 mg.kg-1.day-1 (high-dose amiodarone), or no amiodarone (control group). After 1 week of treatment, programmed electrical stimulation was repeated, and plasma and myocardial amiodarone and desethylamiodarone concentrations were measured. In the control group, sustained ventricular tachycardia or ventricular fibrillation was induced in six dogs (p = NS) when compared with baseline data. In the low-dose amiodarone group, sustained ventricular tachycardia or ventricular fibrillation was induced only in two dogs after 1 week of treatment (p less than 0.01 vs. baseline data). Sustained ventricular tachycardia or ventricular fibrillation was induced in seven dogs after treatment with high-dose amiodarone (p = NS vs. baseline data). Plasma amiodarone concentration in the low-dose amiodarone group (2.54 +/- 1.95 micrograms/mL) was significantly less (p less than 0.01) than that in the high-dose amiodarone group (4.64 +/- 1.66 micrograms/mL). Similarly, the plasma desethylamiodarone in the low-dose amiodarone group (0.32 +/- 0.16 microgram/mL) was significantly less (p less than 0.001) than that in the high-amiodarone dose group (0.56 +/- 0.23 microgram/mL). The myocardial amiodarone concentration in the low-dose amiodarone group (49.7 +/- 23.1 micrograms/g) was significantly lower (p less than 0.001) than that in the high-dose group (98.4 +/- 32.1 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Disposition of amiodarone and its proximate metabolite, desethylamiodarone, in the dog for oral administration of single-dose and short-term drug regimens.

A comparative study of the plasma disposition and tissue distribution of amiodarone and its proximate metabolite, desethylamiodarone, for a single oral dose and short-term oral dosage regimens was conducted in the dog. Four groups of male mongrel dogs (six per group) received one of the following oral dosage regimens: single dose of 40 mg amiodarone/kg; 40 mg amiodarone/kg/day for 10 days and then 30 mg/kg/day for 4 days; 40 mg amiodarone/kg/day for 10 days, 30 mg/kg/day for 4 days, and then no treatment for 14 days; and 40 mg amiodarone/kg/day for 10 days, 30 mg/kg/day for 4 days, and then 20 mg/kg/day for 5 days/week for 2 weeks. The plasma and tissue amiodarone and desethylamiodarone concentrations were determined by HPLC. The plasma concentration of amiodarone was greater than that of desethylamiodarone for the four dosage regimens. The apparent plasma elimination half-life of amiodarone was prolonged following repeated drug administration (3.2 days) compared with a single drug dose (7.5 hr). There was extensive extravascular distribution of amiodarone and desethylamiodarone resulting in progressive tissue accumulation of drug and metabolite for the short-term regimens. For most of the dosage regimens, the concentration of amiodarone was greater than that of desethylamiodarone in left and right ventricles, thyroid gland, adipose tissue, and kidney, whereas the parent drug and metabolite concentrations were similar in lung, liver, and brain. There was predominant accumulation of amiodarone in adipose tissue and desethylamiodarone in lung. After cessation of amiodarone administration, there was rapid elimination of parent drug and metabolite from all tissues, except for amiodarone from adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiarrhythmic effect of chronic oral amiodarone treatment in dogs with myocardial infarction and reproducibly inducible sustained ventricular arrhythmias.

The antiarrhythmic effect of an 8-week oral amiodarone regimen was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Eighteen dogs were randomly assigned to receive either amiodarone, 40 mg/kg/day for 10 days, followed by 30 mg/kg/day for 4 days and then 20 mg/kg/day for 6 weeks (N = 9), or placebo (N = 9). Programmed electrical stimulation was conducted weekly in the two treatment groups. Plasma concentrations of amiodarone and desethylamiodarone were determined weekly, and their myocardial concentrations in the noninfarcted and infarcted regions of the left ventricle were measured at the end of the study. Suppression of inducible arrhythmias was observed at weeks 1,3-7, and 8 in the amiodarone-treated dogs, whereas no suppression occurred in the placebo-treated group. Plasma amiodarone concentration was maximal at 2.5 +/- 1.4 micrograms/ml at week 2, decreased to 1.9 +/- 1.1 micrograms/ml at week 3, and remained steady thereafter. Plasma desethylamiodarone concentrations were in the range of 0.2 +/- 0.1 to 0.4 +/- 0.2 microgram/ml from weeks 1 through 8. Myocardial amiodarone and desethylamiodarone concentrations in the noninfarcted region of the left ventricle were 34.0 +/- 15.8 and 20.8 +/- 7.8 micrograms/g, respectively, at the end of the study. The lack of antiarrhythmic effect of amiodarone at week 2 coincided with the highest plasma amiodarone concentration. The data indicate that this dog model of ventricular arrhythmias is useful for studying the antiarrhythmic action of amiodarone.