benzofurans and Heart-Arrest

Most patients that resuscitate successfully from cardiac arrest (CA) suffer from poor neurological prognosis. DL-3-n-butylphthalide (NBP) is known to have neuroprotective effects via multiple mechanisms. This study aimed to investigate whether NBP can decrease neurological impairment after CA. We studied the protective role of NBP in the hippocampus of a rat model of cardiac arrest induced by asphyxia. Thirty-nine rats were divided randomly into sham, control, and NBP groups. Rats in control and NBP groups underwent cardiopulmonary resuscitation (CPR) 6 min after asphyxia. NBP or vehicle (saline) was administered intravenously 10 min after the return of spontaneous circulation (ROSC). Ultrastructure of hippocampal neurons was observed under transmission electron microscope. NBP treatment improved neurological function up to 72 h after CA. The ultrastructural lesion in mitochondria recovered in the NBP-treated CA model. In conclusion, our study demonstrated multiple therapeutic benefits of NBP after CA.

Topics: Animals; Apoptosis; Asphyxia; Benzofurans; Brain Diseases; Cardiopulmonary Resuscitation; Disease Models, Animal; Heart Arrest; Hippocampus; JNK Mitogen-Activated Protein Kinases; Neurons; Neuroprotection; Neuroprotective Agents; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats, Sprague-Dawley; Return of Spontaneous Circulation; Signal Transduction; tau Proteins; Time Factors

Topics: Benzofurans; Heart Arrest; Humans; Hypoxia-Ischemia, Brain

In this study we investigated the effect of Dl-3-n-butylphthalide (NBP), a clinically used drug for stroke patients in China, on the recovery following cardiac arrest and resuscitation in rats. Male Wistar rats (3-month old) underwent cardiac arrest (12 min) and resuscitation. Rats were randomly assigned to the following groups: sham non-arrested group, vehicle group (vehicle-treated, 7 days before cardiac arrest and 4 days post-resuscitation), NBP pre-treated group (NBP-treated, 7 days before cardiac arrest), and NBP post-treated group (NBP-treated, 4 days post-resuscitation). Overall survival rates and hippocampal neuronal counts were determined in each group at 4 days post-resuscitation. Results showed that NBP pre-treated group (80 %) and NBP post-treated group (86 %) had significantly higher survival rates compared to that of the vehicle group (50 %). At 4 days of recovery, only about 20 % of hippocampal neurons were preserved in the vehicle group compared to the sham non-arrested group. The hippocampal CA1 cell counts in the NBP pre-treated group and NBP post-treated group were significantly higher than the counts in the vehicle group, about 50-60 % of the counts of non-arrested rats. The data suggest that NBP has both preventive and therapeutic effect on improving outcome following cardiac arrest and resuscitation, and NBP might be a potential early phase treatment for patients recovered from cardiac arrest and resuscitation.

Topics: Animals; Benzofurans; CA1 Region, Hippocampal; Disease Models, Animal; Heart Arrest; Male; Neurons; Neuroprotective Agents; Rats, Wistar; Recovery of Function; Resuscitation; Time Factors

Five cases of amiodarone-induced syncope due to torsades de pointes or ventricular fibrillation are described. Amiodarone was used for recurrent supraventricular tachycardia in four cases and frequent ventricular extra systoles complicating congenital QT prolongation in the remaining case. Each was associated with a marked prolongation in the QTc interval following amiodarone. Three cases had had a previous history of life-threatening ventricular arrhythmias secondary to anti-arrhythmic drugs. Hypokalemia may have been a contributory factor in two. The clinical features, predisposing factors, and treatment are discussed.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Failure; Humans; Long QT Syndrome; Tachycardia

During treatment with amiodarone, digoxin and nadolol, asystole occurred repeatedly in a patient with chronic persistent automatic atrial tachycardia. Asystole did not occur after discontinuation of drug therapy, and rechallenge with amiodarone alone produced marked overdrive suppression of all pacemakers resulting in asystole. Amiodarone serum level was within therapeutic range. The possible electrophysiologic mechanisms by which amiodarone might suppress both normal and abnormal pacemakers are discussed. The occurrence of asystole at therapeutic serum concentration of amiodarone suggests that this drug should be used with caution.

Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Digoxin; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Atria; Heart Rate; Humans; Nadolol; Propanolamines; Tachycardia

Multivariate analysis of 11 clinical variables was performed in 104 patients with sustained, symptomatic ventricular tachycardia (VT) or ventricular fibrillation treated with amiodarone to determine variables predictive of subsequent cardiac arrest or sudden death. Twenty-five patients (24%) had fatal or nonfatal cardiac arrest after 7.3 +/- 6.2 months (mean +/- standard deviation) of therapy. Multivariate analysis identified an ejection fraction of less than 0.40, syncope or cardiac arrest before amiodarone therapy, and VT (3 or more consecutive ventricular premature complexes) during predischarge ambulatory electrocardiographic monitoring as variables associated with a high risk of subsequent fatal or nonfatal cardiac arrest (p less than 0.03). Patients who had these 3 clinical variables had a much higher predicted incidence of cardiac arrest at 6 months (62%) and 12 months (76%) than did patients with an ejection fraction greater than 0.40, without syncope or cardiac arrest before amiodarone therapy, and without VT during predischarge ambulatory electrocardiographic monitoring (2% and 5%, respectively) (p less than 0.02). Risk stratification using clinical variables can predict which patients are at high risk of recurrent cardiac arrest or sudden death during amiodarone therapy.

Topics: Aged; Amiodarone; Analysis of Variance; Benzofurans; Death, Sudden; Female; Heart Arrest; Humans; Male; Middle Aged; Recurrence; Risk; Tachycardia; Time Factors; Ventricular Fibrillation

Thirty-three consecutively referred patients with cardiac arrest from ventricular arrhythmias unassociated with a new acute myocardial infarction (AMI) were commenced on amiodarone therapy and followed for a minimum of 12 months. The dose of amiodarone was adjusted to maximum tolerance and not according to the incidence of asymptomatic ventricular premature complex activity. Eight patients died including five sudden deaths. Five out of the eight deaths occurred either within 3 months of therapy or when the dose of amiodarone was less than 400 mg/day. The majority of patients were found to have corneal microdeposits or either thyroid or liver function abnormalities, although none had any clinical manifestation. Ten patients had neurologic side effects. In summary, although the overall cardiac mortality seemed to be reduced by amiodarone therapy and the drug appears to be well tolerated by patients, its role in the prophylaxis against recurrent ventricular fibrillation may be enhanced by a regimen of higher loading and maintenance doses.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Death, Sudden; Dose-Response Relationship, Drug; Drug Evaluation; Female; Follow-Up Studies; Heart Arrest; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Time Factors

There are a number of important drug interactions with amiodarone. This agent appears to have a marked effect on the kinetics of some commonly used cardiovascular drugs, such as warfarin, digoxin, quinidine, and procainamide, and has dynamic interactions with others, such as the beta blockers and some calcium antagonists. Bleeding has been reported, apparently caused by a potentiation of the anticoagulant effect of warfarin by amiodarone. Torsades de pointes has been observed when quinidine, propafenone, or mexiletine is given together with amiodarone. Furthermore, amiodarone may interact with beta-blocking agents and some of the calcium antagonists to produce symptomatic sinus bradycardia and sinus arrest, especially in a latent or overt sick sinus syndrome. During surgery, amiodarone may induce hypotension and an atropine-resistant bradycardia, possibly by interacting with anesthetic agents. A knowledge of the time of onset, extent, duration, and possible mechanisms of the interactions of amiodarone with other cardioactive drugs is still incomplete, but further studies are of great therapeutic importance.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmia, Sinus; Benzofurans; Blood Coagulation Disorders; Calcium; Digoxin; Drug Interactions; Drug Synergism; Heart Arrest; Humans; Kinetics; Quinidine; Tachycardia; Warfarin

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone.

Topics: Aged; Amiodarone; Anorexia; Ataxia; Benzofurans; Female; Heart Arrest; Humans; Lung Diseases; Male; Middle Aged; Nausea; Recurrence; Tachycardia; Thyroid Diseases; Time Factors; Tremor; Ventricular Fibrillation; Vision Disorders

Topics: Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Heart Arrest; Humans; Male; Middle Aged; Tachycardia

Topics: Amiodarone; Benzofurans; Digoxin; Drug Interactions; Heart Arrest; Humans

Topics: Amiodarone; Anesthesia, Local; Benzofurans; Cardiac Pacing, Artificial; Drug Interactions; Heart Arrest; Humans; Lidocaine; Male; Middle Aged; Sick Sinus Syndrome

Topics: Adult; Amiodarone; Aortic Valve Insufficiency; Aprindine; Benzofurans; Cardiomyopathy, Hypertrophic; Drug Interactions; Female; Heart Arrest; Humans; Indenes; Male

Topics: Amiodarone; Benzofurans; Drug Therapy, Combination; Heart Arrest; Humans; Propranolol; Ventricular Fibrillation