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This study investigated the effects of therapeutic and subtoxic doses of digoxin on the risk of ventricular tachycardia (VT) after graded, transthoracic shocks in anesthetized dogs. A series of direct current shocks (5, 10, 25, 50, 75, 100, 150 and 200 J) was delivered to 33 normal dogs and 6 dogs with a healed (32 +/- 7 days) myocardial infarct (MI). In 10 untreated dogs, the duration of post-shock VT was highly reproducible when 3 separate series of shocks were delivered at 2-hour intervals. In 6 normal dogs treated with oral digoxin (0.5 mg/day for 5 to 7 days), a series of shocks delivered before and during treatment (serum levels 1.5 +/- 0.5 ng/ml) resulted in the same duration of post-shock VT. In 18 normal and 6 dogs with MI, a series of shocks was given before and 90 minutes after a therapeutic dose of digoxin (0.05 mg/kg intravenously). At this dose of digitalis (serum level 2.5 +/- 1.0 ng/ml), there was no difference in the duration of post-shock VT in either normal dogs or dogs with MI. A third series of shocks was given after achieving subtoxic digitalization with additional intravenous digoxin (0.01 mg/kg) every 30 minutes until a premature ventricular stimulus evoked a repetitive ventricular response. The subtoxic doses of digitalis (serum levels 13.9 +/- 4.7 ng/ml) increased the duration of post-shock VT in both normal dogs (100%) and dogs with MI (700%) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The natural history of dilated cardiomyopathy is variable, and the prognosis difficult to predict. Several clinical and hemodynamic parameters have been proposed as prognostic indicators. Reports on the relationship between ventricular arrhythmias, degree of hemodynamic impairment, and sudden death are controversial. To define accurately the prognosis in dilated cardiomyopathy, 55 patients with this clinical syndrome underwent clinical evaluation, radionuclide ventriculography, echocardiography, 12-lead electrocardiography, and 24 hr ambulatory monitoring, and the data thus obtained were evaluated based on predictive value. Over a follow-up period of 14.1 +/- 7.9 months, 11 patients (20%) died, all suddenly. Univariate analysis revealed that patients with more severe functional impairment (P = 0.0449), lower cardiac index (P = 0.0226), lower ejection fraction (P = 0.0426), and higher pulmonary artery wedge pressure (P = 0.0314) had greater mortality risk. Age, duration of symptoms, 12-lead electrocardiographic abnormalities, and atrial arrhythmias were not predictive of higher mortality. The number of PVCs per hr, the occurrence of couplets, the degree of PVCs prematurity, and the presence, frequency, rate, and duration of ventricular tachycardia did not have prognostic significance. A stepwise discriminant analysis identified functional class, cardiac index, and presence or absence of multiform PVCs as the group of variables that together could more accurately predict outcome in our dilated cardiomyopathy patients. Using a formula derived from the results of this analysis, the outcomes of 36 of 49 patients (74%) was correctly predicted, with a specificity of 100% and a sensitivity of 70%.

To study the role of the adrenergic nervous system in the genesis of nonlethal reperfusion arrhythmias, the proximal left anterior descending coronary artery was occluded for either 1 or 3 hours in 48 open-chest dogs anesthetized with alpha-chloralose. Heart rate was controlled (90 to 110 beats/min) by bilateral vagotomy and continuous right vagal stimulation. Dogs were treated with either saline, timolol (0.1 mg/kg), or prazosin (0.5 mg/kg) 15 minutes prior to reperfusion. Reperfusion after 1 hour of occlusion in saline-treated dogs evoked sustained polymorphic ventricular tachycardia (204 +/- 9 beats/min) that reverted to sinus rhythm by 15 minutes of reperfusion. The maximum rate of ventricular tachycardia was significantly reduced by both prazosin and timolol. Both drugs also caused about a 50% reduction in the total number of ectopic beats in the first 10 minutes of reperfusion. With a 3-hour occlusion, reperfusion in saline-treated dogs caused sustained polymorphic ventricular tachycardia (135 +/- 15 beats/min) which persisted for several hours. Neither timolol nor prazosin significantly altered the ventricular ectopic rate in these dogs. Furthermore, bilateral stellate transection, left stellate stimulation, isoproterenol (0.5 mg/kg), or methoxamine (100 ug/kg) all failed to alter the ventricular ectopic rate in the saline-treated dogs. Ventricular ectopy induced by reperfusion after a 1- or 3-hour occlusion was overdriven in all dogs by rapid atrial pacing. The results suggest that the nature of reperfusion-induced ventricular ectopy is highly dependent upon the preceeding duration of coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine if the sympathetic nervous system exerts an arrhythmogenic effect on the ischemic myocardium independent of heart rate, the proximal circumflex coronary artery was occluded for 1 h in 62 open-chest, anesthetized dogs. The atrial rate was maintained at 200/min, and the vagosympathetic trunks were transected in all dogs. The total incidence of ventricular fibrillation was 35% in 20 dogs with intact stellates and not significantly different from the incidence of ventricular fibrillation (15%) in another 20 dogs in which both stellate ganglia had been decentralized. Electrical stimulation of the left ansae subclavia (3 Hz, 2 ms, 6-8 V) in the remaining 22 dogs significantly increased the incidence of ventricular fibrillation to 73% (P less than 0.05). The magnitude of S-T segment elevation in the lead II electrocardiogram 90 s after occlusion was 0.69 +/- 0.08 mV in the group with left ansae stimulation and significantly elevated (P less than 0.01) compared with dogs with intact stellates (0.35 +/- 0.06 mV) and with the denervated dogs (0.19 +/- 0.05 mV). The data indicate that the sympathetic nervous system is capable of a direct arrhythmogenic influence on the ischemic myocardium independent of heart rate. The rate-independent arrhythmogenic effects of the sympathetic nervous system may be mediated by an increase in severity of the ischemic insult.

A prospective study was undertaken to assess the response of patients with idiopathic dilated cardiomyopathy to programmed electrical stimulation (PES). Fifteen patients undergoing evaluation of congestive heart failure were studied. All patients underwent cardiac catheterization and coronary angiography as well as endomyocardial biopsy to exclude known causes of heart failure. No patient had a history of syncope or sustained ventricular arrhythmias. All patients were found to have severe left ventricular dysfunction (mean ejection fraction 17%), as well as nonsustained ventricular tachycardia on ambulatory monitoring or exercise testing. A protocol using up to two premature stimuli and burst pacing, from two right ventricular sites, induced up to four repetitive ventricular responses but failed to induce a sustained ventricular arrhythmia in any patient. Patients with dilated cardiomyopathy, advanced ventricular arrhythmias, and depressed left ventricular function respond differently than do patients with coronary artery disease, advanced ventricular arrhythmias, and depressed left ventricular function, to PES. PES appears to have limited value in the evaluation of patients with dilated cardiomyopathy and nonsustained ventricular arrhythmias.

To examine the role of adrenergic influences on genesis of ischemic and reperfusion arrhythmias, the left anterior descending coronary artery (LAD) was cannulated and perfused by a shunt from the left carotid artery in 38 open-chest pentobarbital-anesthetized dogs. Ischemia was produced by shunt occlusion and retrograde diversion of collateral flow from the LAD. The diverted blood was collected and returned to the animal by intravenous (i.v.) injection. The shunt was opened and the ischemic myocardium reperfused after 30 min of ischemia. Microsphere injections in six dogs during shunt occlusion and retrograde bleeding showed that blood flow to the ischemic zone was less than 1.5% of normal zone flow. The remaining 32 dogs were randomized into four treatment groups. Dogs (n = 8) were treated before shunt occlusion with either saline, nadolol (1 mg/kg), prazosin (0.2 mg/kg), or bilateral stellate transection. As compared with saline treatment, nadolol and stellate transection significantly reduced heart rate (HR), and prazosin significantly reduced mean arterial blood pressure (MAP) (p less than 0.05). However, none of the antiadrenergic interventions significantly reduced the number or frequency of ectopic beats during either the 1a or 1b phases of ischemia. None of the 32 dogs developed ventricular fibrillation (VF) during ischemia, but all dogs fibrillated within 30 s of reperfusion. The size of the ischemic zone ranged from 21 to 38% of the left ventricle, and there were no differences among the four treatment groups. The results suggest that when ischemia is severe, the adrenergic nervous system does not play a significant role in genesis of ischemic-induced ectopy or reperfusion-induced VF.

Striking electrocardiographic abnormalities have been noted in some patients with central nervous system injury. To study the relationship between the electrocardiogram and intracranial pressure, intracranial pressure was elevated in 14 open chest pentobarbital-anesthetized dogs. The right vagus was stimulated to produce sinus slowing and the right atrium was paced at a constant cycle length fast enough to prevent arrhythmias and maintain heart rate constant (750 msec in 11 dogs and 600 msec in three dogs). In nine dogs, intracranial pressure was sequentially elevated to 100, 150, and 200 mmHg. Systolic arterial blood pressure consistently rose to exceed intracranial pressure (P less than 0.005). At a pressure of 150 and 200 mmHg, mean QT intervals shortened significantly in recorded leads II, X, Y, and Z from 0.01). T wave changes were also noted that consisted of increasing positivity in leads II, X, and Y and increasing negativity in lead Z. To delinate the role of the sympathetic nervous system, an additional five dogs were subjected to an intracranial pressure of 200 mmHg before and after bilateral stellate ganglionectomy and timolol (0.1 mg/kg IV). Elimination of sympathetic influences did not significantly alter the electrocardiographic effects of elevated intracranial pressure. Thus, intracranial hypertension results in significant QT shortening and T wave changes that are not entirely mediated by the sympathetic nervous system.