ABSTRACT
The majority of patients with implanted cardioverter defibrillators (ICD) require antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements. This study investigated the effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and 80% successful defibrillation energy (ED50, ED80) was calculated in four phases: predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n = 6) with only Tyrode's solution infusion indicated that the preparation was stable over time. Defibrillation energy requirements significantly (p < 0.05) increased with all ARs. Low, medium, and high lidocaine concentrations increased ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively. Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%, respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158, 212, and 286%, respectively. The results of this study demonstrate a dose-dependent increase in defibrillation energy requirements by using lidocaine, diltiazem, and ajmaline. In patients with ICDs, administration of these drugs might cause a critical increase in defibrillation energy requirements, resulting in device failure.
Subject(s)
Ajmaline/toxicity , Anti-Arrhythmia Agents/toxicity , Cardiovascular Agents/toxicity , Defibrillators, Implantable , Diltiazem/toxicity , Lidocaine/toxicity , Ventricular Fibrillation/therapy , Ajmaline/therapeutic use , Analysis of Variance , Animals , Anti-Arrhythmia Agents/therapeutic use , Cardiovascular Agents/therapeutic use , Diltiazem/therapeutic use , Disease Models, Animal , Dose-Response Relationship, Drug , Electric Countershock , Electrocardiography/drug effects , Equipment Failure , Female , Heart/drug effects , In Vitro Techniques , Lidocaine/therapeutic use , Male , RabbitsABSTRACT
In search for an effective treatment of human poisonings with ajmaline, a potent antiarrhythmic drug, the use of specific antibodies as neutralizing agents was explored in a preliminary animal model. For this purpose, New Zealand white rabbits were immunized with the antigen obtained after coupling the 17-hemisuccinate ester of ajmaline-21-acetate to bovine serum albumin, whereas other rabbits were immunized with the protein carrier only. While seven control rabbits receiving 0.625 mg/kg/min. ajmaline intravenously until death, died within 54.8 +/- 5.2 min. death was delayed until 137.7 +/- 15.5 min in seven ajmaline bovine serum albumin-immunized rabbits (p less than 0.001). Three bovine serum albumin-immunized rabbits behaved as controls. These results provide evidence that an immunological protection against ajmaline toxicity can be obtained in laboratory animals.
Subject(s)
Ajmaline/toxicity , Ajmaline/immunology , Animals , Growth Hormone , Peptide Fragments , Rabbits/immunology , Time FactorsSubject(s)
Ajmaline/pharmacology , Anti-Arrhythmia Agents , Ethylenediamines/pharmacology , Hemodynamics/drug effects , Propranolol/pharmacology , Quinidine/pharmacology , Ajmaline/toxicity , Animals , Arrhythmias, Cardiac/chemically induced , Barium/pharmacology , Blood Pressure/drug effects , Cats , Dogs , Ethylenediamines/toxicity , In Vitro Techniques , Propranolol/toxicity , Quinidine/toxicity , Rabbits , Rats , Strophanthins/pharmacology , Time FactorsSubject(s)
Ajmaline/analogs & derivatives , Anti-Arrhythmia Agents , Aconitine , Ajmaline/pharmacology , Ajmaline/toxicity , Animals , Chemical Phenomena , Chemistry , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Electrocardiography , Female , Injections, Intravenous , Lethal Dose 50 , Rats , Structure-Activity RelationshipSubject(s)
Ajmaline/pharmacology , Hemodynamics/drug effects , Administration, Oral , Ajmaline/analogs & derivatives , Ajmaline/toxicity , Animals , Anti-Arrhythmia Agents , Blood Pressure/drug effects , Cats , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Heart Conduction System/drug effects , Heart Rate/drug effects , Injections, Intravenous , Lethal Dose 50 , Propranolol/pharmacology , Rabbits , RatsSubject(s)
Ajmaline/analogs & derivatives , Anti-Arrhythmia Agents/toxicity , Ajmaline/toxicity , Alkaline Phosphatase/blood , Blood Cell Count , Blood Glucose , Body Weight/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Hemoglobins , Hydrogen-Ion Concentration , Kidney Function Tests , Lethal Dose 50 , Liver/pathology , Liver Function TestsABSTRACT
The antiarrhythmic drugs ajmaline and its 17-monochloroacetate ester (MCAA; Rtimos-Elle) were studied in cats. MCAA was less than half as toxic as ajmaline. Non-lethal doses of MCAA decreased blood pressure before heart rate, whereas ajmaline initially decreased heart rate. Both drugs prolonged the PR, QRS and QT intervals of the EKG. Recovery of these effects was within one hr. MCAA (10 mg/kg) and ajmaline (4.05 mg/kg) were studied separately by a one and 10 min infusion in the same cat. The dose of MCAA was ten times the usual dose in man and that of ajmaline four times the usual clinical dose. More marked effects were observed with the one min infusion. Arrhythmias were usually observed with ajmaline, but not with MCAA, even though it was rapidly converted to ajmaline. Maximal cardiovascular effects of MCAA and ajmaline were observed within 3 min of the end of infusion, which was also the time of peak blood levels. The elimination of MCAA resembled the kinetics of a multi-compartment system after a one min infusion. Peak blood levels declined by one-half in 3 min. Ajmaline blood levels declined linearly, with a half-life of 100 min, after a one min infusion. The peak blood level of MCAA after an intraduodenal dose of 25 mg/kg occurred at 20 min, whereas the peak blood level of the ajmaline formed occurred at 4 hr. In conclusion, MCAA has some different pharmacological properties and different kinetics of elimination than ajmaline.
