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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was designed to investigate whether long-term use of aprindine can prevent sudden death from primary ventricular fibrillation. Patients with a proven recent myocardial infarction and malignant ventricular arrhythmias occurring late after the acute episode were asked to participate in a 1-yr, double-blind, randomized, placebo-controlled trial to suppress the rhythm disturbances observed on an ambulatory electrocardiogram. Particular care was taken to monitor drug adherence. Arrhythmia detection by ambulatory electrocardiography was used to assess drug efficacy; side-effects establish the maximum tollerated dose for each individual patient. Aprindine was therefore used under optimal circumstances. An interactive computer system served as a data base and provided the investigators and the monitoring committee with all the information required for a proper evaluation of the progress of the study.
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PMID:Design of a study to evaluate drug therapy of serious ventricular rhythm disturbances after an acute myocardial infarction. 33 7

A 48 year old man with severe coronary artery disease died approximately 33 hours after swallowing unknown amounts of aprindine, digoxin, furosemide, acenocoumarol, flurazepam, nitrazepam and lorazepam. Blood analysis carried out 40 min. before death showed no hydric or ionic imbalance; blood gases were normal. Serum digoxin concentration was 3.9 ng/ml; plasma concentration of aprindine was 2.5 mug/ml and plasma concentration of desethylaprindine was 386 ng/ml. Patient was profoundly comatose, hypotensive, and the electrocardiogram showed broad and bizarre QRS complexes; patient ultimately died in irreversible secondary ventricular fibrillation and asystole. Aprindine probably played a decisive role in the fatal outcome of this complex drug intoxication.
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PMID:Suicide with aprindine and digoxin. 108 16

The effectiveness of aprindine, N-[3-(diethyl amino)propyl]-N-phenyl-2-indanamine, was examined against experimentally induced arrhythmias. Ouabain-induced ventricular tachycardia was reversed in six of six dogs by aprindine, 5 mg/kg i.v. The threshold for extrasytoles induced by a 250-msec train of 60 Hz 2-msec pulses starting 75 msec after the pacing pulse was elevated from a control value of 0.18 +/- mA to a peak of 0.29 +/- 0.03 mA 5 minutes after aprindine, 5 mg/kg (P less than .005). The similarly determined ventricular fibrillation threshold was increased from a control value of 2.45 +/- 0.78 mA to a maximum of 5.68 +/- 1.47 mA 30 minutes after aprindine, 5 mg/kg i.v. (P less than .025). Aprindine failed to protect against fibrillation associated with one-stage occlusion and release of the left anterior descending coronary artery. Conscious dogs 24 hours after two-stage ligation of the left anterior descending coronary artery showed ectopic beats averaging 107 +/- 5 beats/min. Aprindine, 5 mg/kg i.v., caused an initial reduction of the ectopic rate to 1 +/- 1 beats/min (P less than .001) returning to 57 +/- 19 beats/min (P less than .05) 30 minutes postdrug. An additional 5 mg/kg dose reduced the ectopic rate to 1 +/- 1 beats/min (P less than .001) returning to 15 +/- 8 beats/min (P less than .005) 60 minutes after drug. Evaluation of these animals at 48 hours showed a similar pattern, although one animal fibrillated after 5 mg/kg of aprindine. Aprindine is an effective antiarrhythmic agent in some experimental cardiac arrhythmias, but the appearance of central nervous system toxicity at therapeutic drug concentrations in conscious animals indicates that it may have a narrow margin of safety.
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PMID:Antiarrhythmic and antifibrillatory properties of aprindine. 115 68

The effects of aprindine and disopyramide on reperfusion-induced arrhythmias and cardiac function were investigated in the isolated perfused rat heart. Occlusion of the left anterior descending coronary artery for 15 min and subsequent reperfusion provoked ventricular tachycardia in 9 out of 10 hearts and ventricular fibrillation in 7 out of 10. Aprindine or disopyramide was infused 15 min prior to the coronary occlusion in concentrations of 0.1 and 5.4 micrograms/ml, which were comparable to therapeutic free plasma concentrations in patients. Aprindine significantly decreased the incidence of ventricular tachycardia and fibrillation, compared with control (2/10, p less than 0.01 and 1/10, p less than 0.05, respectively). Disopyramide depressed only the occurrence of ventricular tachycardia (3/10, p less than 0.05). Neither of the drugs induced changes in heart rate, left ventricular systolic pressure, coronary flow or PR intervals, but they significantly improved the recovery of the left ventricular systolic pressure within 15 min after reperfusion, at which time most of the hearts had restored sinus rhythm. It is concluded that, at clinically effective concentrations, aprindine and disopyramide inhibit reperfusion-induced arrhythmias without deteriorating cardiac function in the isolated rat heart.
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PMID:Effects of aprindine and disopyramide on reperfusion-induced arrhythmias and cardiac function in isolated rat hearts. 261 22

Pharmacologic prevention of ventricular fibrillation (VF) and sudden cardiac death (SCD) is based on the assumption that the abnormal impulse that causes premature ventricular complexes (PVCs) may trigger VF and that antiarrhythmic drug therapy will thus inactivate the trigger. However, results available from secondary preventive trials of antiarrhythmic agents, including the Ghent-Rotterdam Aprindine (GRAP) study, have not established conclusively the value of antiarrhythmic therapy. A number of factors could explain this failure, e.g., PVCs and VF might not be causally related, thus, antiarrhythmic drugs might not prevent VF; the number of patients enrolled in investigations might have been too small to accommodate statistical proof of benefit; or the subjects might have been poorly selected. A serious design defect that could interfere with demonstrating a benefit for treatment might arise from the fact that all patients in the GRAP and similarly designed studies had to show complex ventricular arrhythmias at randomization and that antiarrhythmic treatment was usually continued regardless of its effect on the underlying arrhythmias. Given the variability of arrhythmias, it would be expected that arrhythmias would persist in only a fraction of patients randomized to placebo. However, arrhythmias also persisted, although to a lesser extent, in treated patients. If one considers that SCD risk may be reduced in the face of arrhythmia suppression but that it may be increased if the arrhythmia persists due to a toxic or proarrhythmic drug effect, any advantageous effects of successful antiarrhythmic drug therapy would be offset by the negative effects of unsuccessful arrhythmia suppression, which would distort the comparison with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical trials of antiarrhythmic therapy--an improper answer to a proper question? 330 38

Sixty-four patients with a history of ventricular tachycardia and ventricular fibrillation refractory to conventional therapy received aprindine to abolish recurrent episodes of symptomatic ventricular tachycardia. Fifty-six patients became asymptomatic and were followed up for a mean period of 23 months. Aprindine dose was adjusted to minimize adverse reactions but still control arrhythmia. Survival analysis was performed for the group with aprindine levels greater than 1.5 micrograms/ml and the group with levels of 1.5 micrograms/ml or less. At the end of the study, 65% of the patients with a high level were alive and asymptomatic as compared with only 35% of the patients with a low level (p less than 0.036). In patients at risk of recurrent sudden cardiac death, high aprindine levels maintained after abolition of symptomatic ventricular tachycardia were associated with improved survival.
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PMID:The utility of aprindine blood levels in the management of ventricular arrhythmias. 397 73

The effect of aprindine, verapamil and nifedipine on electrical stimulation threshold (EST) and ventricular fibrillation threshold (VFT) was studied in isolated rabbit hearts. Aprindine steeply raised EST and VFT in a dose-dependent manner. With the highest concentration of aprindine tested (0.56 mumol/l), protection against electrically-induced ventricular fibrillation was achieved in 4 out of 6 hearts after 60 min exposure to the drug. Perfusion with verapamil (0.1 and 0.2 mumol/l) and nifedipine (0.14 and 0.21 mumol/l) produced significant rise in both thresholds. When the hearts were perfused with higher concentration (0.3 mumol/l verapamil, 0.28 mumol/l nifedipine), EST and VFT did not continue to be increased in a dose-dependent manner but actually dropped below the control value in most hearts. These results suggest that the effect of aprindine on EST and VFT is different from that of verapamil and nifedipine and further indicate a limited effectiveness of these two slow channel blockers against ventricular fibrillation.
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PMID:Effect of aprindine, verapamil and nifedipine on ventricular fibrillation threshold in isolated rabbit hearts. 401 63

The effectiveness of three new antiarrhythmic drugs, aprindine, mexiletine and tocainide in elevating ventricular fibrillation threshold measured in the Langendorff-perfused rabbit heart and in protecting against ouabain-induced arrhythmias in the Langendorff-perfused guinea-pig heart has been compared with that of lignocaine. All these drugs have produced a significant rise in the threshold but quantitatively mexiletine was about equal to, tocainide five times less and aprindine thirty-eight times more potent than lignocaine in this effect. Aprindine differed from the other three drugs in that it had a slow onset of action and its effect was not entirely removed upon reperfusion with the drug-free solution. Only aprindine and mexiletine provided complete protection against ouabain-induced ventricular fibrillation while 3 of 6 and 4 of 6 hearts fibrillated in the presence of lignocaine or tocainide respectively.
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PMID:The antifibrillatory potency of aprindine, mexiletine, tocainide and lignocaine compared on Langendorff-perfused hearts of rabbits and guinea-pigs. 611 Jul 21

Little information exists regarding the effects of coronary artery occlusion on the distribution and actions of antiarrhythmic agents. We administered aprindine to dogs before, 5 min after, and 24 h after one-stage left anterior descending coronary artery (LAD) occlusion. Coronary artery occlusion performed after aprindine administration slowed the rate of disappearance of aprindine from the ischaemic zone compared with the normal zone, so that ischaemic zone aprindine concentrations averaged more than twice normal zone aprindine concentrations 1 h after LAD occlusion. When LAD occlusion was performed before aprindine administration, ischaemic zone aprindine concentrations were initially less than 15% of normal zone aprindine concentrations and increased with time to approach half of normal zone aprindine concentrations 70 min after LAD occlusion. Seventeen of 35 dogs (49%) receiving aprindine before LAD occlusion experienced sustained ventricular tachycardia or ventricular fibrillation, compared with 5/34 (14%) receiving aprindine immediately after LAD occlusion (P less than 0.01), 1/10 (10%) undergoing LAD occlusion without receiving aprindine (P less than 0.05) and 0/16 receiving aprindine without LAD occlusion (P less than 0.01). Aprindine administered 24 h after CO reduced premature ventricular complexes from a mean of 35 to 12 per 100 beats (P less than 0.01) occlusion importantly modifies the regional myocardial distribution of aprindine and its effects on ventricular arrhythmias after coronary artery occlusion.
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PMID:Alterations in regional myocardial distribution and arrhythmogenic effects of aprindine produced by coronary artery occlusion in the dog. 726 Sep 80

Acute coronary syndrome causes several types of arrhythmia because of its electrical instability and ischemia. The most important arrhythmia is ventricular tachycardia which degenerates to ventricular fibrillation. Prompt direct current cardioversion will be needed and prevention of ventricular tachyarrhythmia by potassium channel blocker became more popular in Japan. Nifekalant or amiodarone should be selected. Atrial fibrillation also occurred in the patients with acute coronary syndrome, and it may deteriorate hemodynamics condition. Therefore, termination and prevention of atrial fibrillation is another important issue in acute coronary syndrome. Aprindine, amiodarone, or bepridil will be the choice to prevent recurrent atrial fibrillation after direct current cardioversion.
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PMID:[Strategy for cardiac arrhythmias in acute coronary syndrome]. 1661 91


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