Contrast-medium-induced ventricular fibrillation: arrhythmogenic mechanisms and the role of antiarrhythmic drugs in dogs

RATIONALE AND OBJECTIVES: Small electrolyte additions to a nonionic contrast medium reduce the risk of ventricular fibrillation (VF) during wedged catheter injection of a contrast medium. The current study was designed to further investigate contrast-medium-induced VF by studying the effect of pretreatment with different antiarrhythmic drugs. METHODS: During a simulated wedged catheter situation, iohexol was injected into the anterior descending branch of the left coronary artery in five open-chest, anesthetized dogs pretreated with lidocaine, propranolol, amiodarone, almokalant, or verapamil. RESULTS: Wedging the catheter for 60 sec did not induce VF. However, all 15 wedged catheter injections with iohexol induced VF within 28 sec (19 +/- 1 [mean +/- standard error of the mean]) despite pretreatment with antiarrhythmic drugs. Prior to VF, conduction was slowed and monophasic action potential duration lengthened in the contrast-medium-perfused myocardium, although no significant changes occurred in the control area. CONCLUSION: The combination of catheter wedging and long-lasting contrast medium injection has a high risk of causing VF. Although adding a small amount of electrolytes to nonionic contrast media can reduce the risk of VF, antiarrhythmic drug therapy may not have a protective effect.     

Effects of the novel antiarrhythmic agent azimilide on experimental atrial fibrillation and atrial electrophysiologic properties

OBJECTIVES: This study was designed to evaluate how the atrial electrophysiological and antiarrhythmic effects of azimilide compare with those of the specific rapid delayed rectifier (IKr) blocker dofetilide. BACKGROUND: Azimilide, a new class III drug, was initially believed to be a highly selective blocker of the slow delayed rectifier (IKs), but recent studies suggest that azimilide potently blocks IKr. Thus, it has been suggested that azimilide's in vivo effects may simply be due to IKr blockade. METHODS: Dose regimens producing stable effects over time were developed, and two dose levels of azimilide (10 and then 20 mg/kg) or dofetilide (0.08 and then 0.16 mg/kg) were administered to morphine/chloralose-anesthetized dogs during sustained vagal atrial fibrillation (AF). Epicardial mapping was used to measure conduction velocity and AF cycle length. RESULTS: Azimilide terminated AF in 13/14 dogs (93%), while dofetilide terminated AF in 6/12 (50%, P < 0.05). While dofetilide had strong reverse use-dependent effects on atrial ERP (e.g. at lower doses, dofetilide increased ERP by 51 +/- 3% at a basic cycle length, BCL, of 400 ms and by 17 +/- 3% at a BCL of 200 ms), azimilide's effects on ERP were rate-independent (ERP increased at lower dose by 38 +/- 6%, BCL 400 ms; 35 +/- 10%, BCL 200 ms). Neither drug affected conduction. CONCLUSIONS: Azimilide is effective against experimental AF, and increases ERP with a frequency dependence different from the IKr blocker dofetilide, suggesting that azimilide's actions on atrial tissue cannot be attributed exclusively to IKr block, and that effects on other currents (such as IKs) are likely to be important.     

Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter

The results of nineteen semiconstrained modified Coonrad-Morrey total elbow arthroplasties performed in nineteen patients to treat instability were evaluated at an average of seventy-two months (range, twenty-five to 128 months) postoperatively. Preoperatively, all patients had either a flail elbow or gross instability of the elbow that prevented useful function of the extremity. The instability of sixteen elbows was the result of a traumatic injury or of the treatment of such an injury. The most recent result was satisfactory for sixteen elbows and unsatisfactory for three. The average overall Mayo elbow performance score increased from 44 points preoperatively to 86 points postoperatively. At the most recent follow-up examination, no elbow was unstable. The average arc of flexion was from 25 degrees (range, 0 to 60 degrees) to 128 degrees (range, 30 to 142 degrees), which represented a 58-degree increase from the preoperative average arc. Sixteen patients had little or no pain after the arthroplasty. There were four complications in four patients. Three complications (loosening of the humeral component in one patient and a fracture of the ulnar component in two) occurred postoperatively; all three were treated with a revision procedure. The other complication (a fracture of the olecranon) occurred intraoperatively and was treated with tension-band fixation; the most recent outcome was not affected. Radiographically, one patient had complete (type-V) radiolucency about the humeral component. None of the nine patients for whom true anteroposterior radiographs were available had evidence of wear of the bushings. The bone graft behind the anterior flange of the humeral prosthesis was mature in fourteen elbows, incomplete in two, and resorbed in two. One patient was excluded from this analysis because radiographs were not available. Instability of the elbow resulting in the inability to use the extremity is a challenging clinical situation. However, in patients who are more than sixty years old and in selected patients who are less than sixty years old but who have extensive loss of bone as a result of severe injury, have had multiple operations, or have rheumatoid arthritis, total elbow arthroplasty with a linked, semiconstrained prosthesis reestablishes a mobile, stable joint without premature loosening or failure of the components. In our experience, the use of customized implants, maintenance of the muscular attachments to the epicondyles, and reconstruction of the epicondyles to the implant were unnecessary.     

Tachycardia-induced change of atrial refractory period in humans: rate dependency and effects of antiarrhythmic drugs

BACKGROUND: Atrial fibrillation (AF) has been shown to shorten the atrial effective refractory period (ERP) and make the atrium more vulnerable to AF. This study investigated the effect of atrial rate and antiarrhythmic drugs on ERP shortening induced by tachycardia. METHODS AND RESULTS: Seventy adult patients without structural heart disease were included. For the first part of the study, right atrial ERP was measured with a drive cycle length of 500 ms before and after 10 minutes of rapid atrial pacing using five pacing cycle lengths (450, 400, 350, 300, and 250 ms) in 10 patients. For the second part of the study, the remaining 60 patients were included to study the effects of antiarrhythmic drugs on changes in atrial ERP induced by AF. Atrial ERP was measured with a drive cycle of 500 ms before and after an episode of pacing-induced AF. After the patients were randomized to receive one of six antiarrhythmic drugs (procainamide, propafenone, propranolol, dl-sotalol, amiodarone, and verapamil), atrial ERP was measured before and after another episode of pacing-induced AF. In the first part of the study, atrial ERP shortened significantly after 10 minutes of rapid atrial pacing, and the degree of shortening was correlated with pacing cycle length. The second part of the study showed that atrial ERP shortened after conversion of AF (172+/-15 versus 202+/-14 ms, P<0.0001) and that ERP shortening was attenuated after verapamil infusion (-4.6+/-1.2% versus -15.1+/-3.4%, P<0.001) but was unchanged after infusion of the other antiarrhythmic drugs. Furthermore, all of these antiarrhythmic drugs could decrease the incidence and duration of secondary AF. CONCLUSIONS: The atrial ERP shortening induced by tachycardia was a rate-dependent response. Verapamil, but not other antiarrhythmic drugs, could markedly attenuate this effect. However, verapamil and the other drugs could decrease the incidence and duration of secondary AF.     

Myocardial infarction related atrial fibrillation: role of endogenous adenosine

Hyperglycemia and hypokalemia caused by catecholamine discharge have been reported to occur in patients after severe head trauma. The aim of this prospective study was to evaluate whether a similar neuroendocrine and metabolic response is found in children after minor head trauma such as brain concussion (Glasgow Coma Scale (GCS) > or = 13). One hundred fifty patients aged 2 to 14 years (average, 6 years) were divided into three groups (n = 50 in each group). Group 1 included patients admitted to the emergency department for brain concussion (Glasgow Coma Scale (GCS) > or = 13); group 2 included patients admitted for fractures of long bones without head injury; and group 3 were control patients electively admitted for hernia repair. All patients had complete physical and neurological examinations. Complete blood count and blood chemistry were obtained on admission. All blood tests were repeated at 6, 12, and 24 hours in patients belonging to group 1. An electrocardiogram was obtained in selected patients and catecholamine levels were measured in some patients. Statistical analysis was performed using analysis of variance (ANOVA). Serum potassium and sodium levels in patients with brain concussion (group 1) were 3.6 +/- 0.6 and 136 +/- 3 mEq/L, respectively and were significantly lower (P < 0.01) than those in patients belonging to group 2, 4 +/- 0.4 and 138 +/- 3, respectively, and the controls (group 3), 4.2 +/- 0.5 and 140 +/- 2, respectively. Serum glucose level was 124 +/- 34 and 118 +/- 32 mg% in groups 1 and 2 and was significantly higher than that of the controls (group 3), 90 +/- 23 mg%. There was no correlation between serum electrolytes and GCS. No electrocardiogram changes or elevation of serum catecholamines were found. Hypokalemia resolved spontaneously within 24 hours. All patients recovered without neurological sequalae. Transient hypokalemia frequently occurs in children even with minor head trauma. This hypokalemia resolves spontaneously, without treatment and within 24 hours.     

Response of atrial fibrillation to therapy: role of etiology and left atrial diameter

Left atrial diameter was measured by echocardiography in 107 patients in atrial fibrillation. The etiology of atrial fibrillation was rheumatic heart disease with predominant mitral valve involvement (RHD) in 51 patients and idiopathic atrial fibrillation (IAF) in 56. The left atrial diameter was correlated to the patient's response to therapy. The mean left atrial diameter was 3.4 cm in patients with paroxysmal atrial fibrillation, 3.8 cm in those requiring direct current (DC) cardioversion, and 4.4 cm in patients with persistent atrial fibrillation. However, in each of these therapeutic response groups, the left atrial diameter was signficantly smaller in patients with idiopathic atrial fibrillation. In the group with paroxysmal atrial fibrillation, the mean left atrial diameter was 4.3 +/- .7 cm in patients with RHD, compared to 3.1 +/- .6 cm in those with IAF (p less than .001). In the group requiring DC cardioversion, the left atrial diameter was 4.7 +/- .8 cm in patients with RHD compared to 3.6 +/- .5 cm in those with IAF (p less than .01). In patients with persistent atrial fibrillation, the left atrial diameter was 5.2 +/- .9 cm in patients with RHD and 4.0 +/- 1.0 cm in IAF (p less than .001). Left atrial diameter as well as the etiology of the heart disease are important in determining the response of atrial fibrillation to therapy.     

Beta-adrenergic blockade as adjunctive oral therapy in patients with chronic atrial fibrillation

In many patients with chronic atrial fibrillation, it is difficult to prevent an excessive ventricular rate under stress, even with high levels of digoxin in the blood. The effect of adding beta-adrenergic blockade with practolol to digoxin on the heart rate at rest and during low-grade controlled exercise was investigated in 28 patients with chronic atrial fibrillation and in ten normal control subjects who were receiving maintenance dosages (0.25 to 0.75 mg) of digoxin. In atrial fibrillation, therapy with practolol decreased the mean heart rate at rest from 99.8 beats per minute to 77.5 beats per minute (23 percent reduction; P less than 0.01) and during mild exercise from 148.9 beats per minute to 105.4 beats per minute (29 percent) reduction (P less than 0.001). Fifteen patients had clinically significant heart failure; therapy with practolol did not worsen it. Reversible side effects were detected in two patients. When therapy with digoxin is not sufficient to control atrial fibrillation, the addition of a beta-adrenergic blocking agent is recommended as adjunctive treatment in selected patients.     

New evolvement of antiarrhythmic drugs

The Cardiac Arrhythmia Suppression Trial (CAST) casted serious doubts on the usefulness of Class I antiarrhythmic drugs, causing us to turn our attention from drugs impairing conduction of excitation in the myocardium by blocking sodium channels toward those producing increased refractoriness of myocardial cells by blocking potassium channels. This change in the direction of thinking from the "Na+ channel paradigm" to "K+ channel paradigm" resulted in the generation of newly synthetized Class III drugs that have the common electrophysiological property of suppressing outward K+ currents (IK, IK1, Ito) without affecting inward currents (INa, ICa). However, their reversed use-dependence of action potential duration prolonging effect contributes to their untoward action of proarrhythmias. It is still controversial if ion channel blockers acting solely on a certain kind of ion channels are more beneficial than drugs having compound actions such as amiodarone or sotalol. Molecular biology, if combined with arrhythmology, is expected to provide new chemical and pharmacological bases for creating novel antiarrhythmic drugs.     

Amiodarone in atrial fibrillation

BACKGROUND: The endocrine, metabolic, and immunologic changes during pregnancy give rise to a number of physiologic cutaneous changes. OBJECTIVE: We evaluated 140 pregnant women to determine the pattern of pregnancy-induced physiologic skin changes in our community. RESULTS: The various changes observed include: increased pigmentation (90.7%), striae (77.1%), edema (48.5), melasma (46.4%), vascular changes (34.2%), and others. CONCLUSIONS: Pigmentary changes were the most common finding, whereas the incidence of vascular changes was quite low (p < 0.01).     

Cardioversion of atrial fibrillation

Cardioversion to sinus rhythm should be considered for all patients in atrial fibrillation in order to improve cardiac performance and perhaps to reduce the long-term risk of thromboembolic complications. Different methods of cardioversion, whether electrical or pharmacological, exist and there is often uncertainty about performing the procedure. In particular, there is often confusion about the use of anti-arrhythmic drugs and the suitable length of anticoagulant therapy required pre- and post-cardioversion. This review discusses the current understanding of electrical and pharmacological cardioversion of atrial fibrillation, the clinical effects and the role of prophylactic anti-arrhythmic and anticoagulant therapy in this procedure.     

Anticoagulation in nonvalvular atrial fibrillation

Atrial fibrillation is a common cardiac arrhythmia. Management of atrial fibrillation should focus on prevention of thromboembolic complications and the treatment of arrhythmia related symptoms. This article will discuss anticoagulant therapy in nonvalvular atrial fibrillation and review results from several controlled trials.     

Preventing stroke in atrial fibrillation

Atrial fibrillation, a common cardiac arrhythmia, is now recognized as a powerful risk factor for stroke. Previously, atrial fibrillation was thought to predispose persons to stroke only in the presence of rheumatic heart disease with mitral stenosis. The significant impact of nonvalvular atrial fibrillation on stroke incidence, recurrence and mortality was not fully appreciated. A series of clinical trials have confirmed that a five-fold increase in stroke incidence occurs in patients with atrial fibrillation, and that warfarin anticoagulation is efficacious in stroke prevention. This anticoagulation benefit was achieved with an acceptably low risk of serious hemorrhage.