ajmaline and Chagas-Cardiomyopathy

1. The resting electrocardiogram was obtained from 25 Trypanosoma cruzi-infected rats 30 days after infection (phase I). The resting electrocardiogram was abnormal in 12 (group I) and normal in 13 (group II) animals. Nineteen similar but non-infected animals served as controls. Both the resting electrocardiogram and the ajmaline test were performed 120 and 350 days after infection (phases II and III, respectively). 2. With regard to the resting electrocardiogram of group I animals, left axis deviation was found in 10 of 12 (83%) in phase I, one of 12 (8%) in phase II (P less than 0.05) and in none of phase III (P less than 0.05). An intraventricular conduction delay was found in four of 12 (33%) rats in phase I, two of 12 rats (16%) in phase II (P greater than 0.05) and six of 12 rats (50%) in phase III (P greater than 0.05). The ajmaline test was abnormal in nine of 10 (90%) rats of group I with normal resting electrocardiogram in phase II, and in three of six (50%) animals in phase III (P greater than 0.05). 3. An intraventricular conduction delay was found in the resting electrocardiogram of one of 13 (7%) rats of group II in phase III. The ajmaline test was abnormal in one of 13 (7%) rats in phase II and in one of 12 (8%) rats in phase III. 4. No control rat showed pathological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ajmaline; Animals; Chagas Cardiomyopathy; Electrocardiography; Male; Myocardium; Rats

Forty-one chronically T. cruzi-infected male adult albino rats with normal resting ECG were submitted to the ajmaline test (1 mg/kg body weight injected into the dorsal vein of the penis). Twenty-one similar noninfected animals served as controls. Ajmaline induced the following ECG alterations in control rats: A decrease in heart rate, an increase in heart rate, an increase in P-wave duration, an increase in PR interval, lengthening of the QRS complex, and left axis deviation in 33%, 28%, 14%, 90%, 100%, and 33% of the animals, respectively. Ajmaline evoked similar alterations in 29 of 41 (71%) T. cruzi-infected rats. However, 12 of 41 (29%) infected rats showed ECG changes of a magnitude not seen in controls: P-wave enlargement, first-degree AV block, lengthened QRS complex, and first-degree AV block plus lengthened QRS complex in 7%, 12%, 14%, and 4% of the animals, respectively. Microscopical lesions were not found in control rats. However, 22 of 41 (53%) infected rats were found to have the following pathological lesions: mononuclear cell infiltrate, necrosis, myocyte vacuolization, and interstitial fibrosis in 56%, 39%, 29%, and 7% of the animals, respectively. By comparing the ECG changes evoked by ajmaline not seen in controls with the concomitant pathological lesions, the ajmaline test was found to have 54% sensitivity, 100% specificity, and 100% positive predictive value. Thus, the ajmaline test appears to be useful for unmasking myocardial disease and therefore may be considered a potential method for the full characterization of the indeterminate form of Chagas' disease in experimental animals.

Topics: Ajmaline; Animals; Chagas Cardiomyopathy; Chagas Disease; Electrocardiography; Heart Rate; Male; Myocardium; Rats; Trypanosoma cruzi

Topics: Ajmaline; Animals; Chagas Cardiomyopathy; Disease Models, Animal; Electrocardiography; Rats

Fifty-eight chronically T. cruzi-infected rats and 26 control rats were submitted to the ajmaline test (1 mg/kg, i.v. during ECG monitoring) after obtaining the resting ECG. Abnormal ECG tracings were detected in the resting ECG of 26 (44%) infected rats. After ajmaline injection, a decrease in heart rate was observed in control but not in infected rats. P wave enlargement, lengthening of the QRS complex, and increase of the PR as well as the QaT intervals were detected in all animals. Ajmaline induced right axis deviation in 7% of the control rats and left axis deviation in 26% of the controls, as well as in 23% of the T. cruzi-infected rats with abnormal resting ECG. However, after ajmaline injection, 7 (21%) of the 32 infected rats having normal resting ECG presented the following ECG changes not observed in control animals: indeterminate axis (15%), marked increase in PR interval and bizarre QRS complex (3%), and marked decrease in heart rate plus a significant increase in PR interval. These data show that ajmaline induces important ECG changes not only in controls, but also in T. cruzi-infected rats. Furthermore, since severe ECG changes occurred only in T. cruzi-infected rats having normal resting ECG, the ajmaline test can be used to unmask cardiac lesions in experimental chronic Chagas' disease.

Topics: Ajmaline; Animals; Chagas Cardiomyopathy; Electrocardiography; Heart Rate; Male; Rats; Rats, Inbred Strains

In the present study, the ajmaline test was applied to T. cruzi-infected rats and evaluated for the ability to reveal ECG disturbances. The test consists of intravenous injection of ajmaline (2 mg/kg body-weight) under ether anaesthesia, and continuous ECG monitoring (right precordial lead: V1 or V2, 100 mm/sec paper speed). The animals used for the test (n = 30) had been experimentally infected with the Colombia strain of T. cruzi (1,000 parasites/g body-weight, newly weaned rats) one year before the experiments. Control non-infected rats (n = 21) were similarly maintained and treated. The ECGs were analysed under baseline conditions, i.e., before ajmaline, and 15, 30, 60 and 180 seconds after completion of ajmaline injection through the dorsal vein of the penis. The following parameters were studied: heart rate, PR interval, QRS and Qat duration. Morphological changes of the QRS complex and ST-T segment were also recorded. Under baseline conditions, the two groups had comparable values for all parameters, except for the PR interval, which was significantly increased in infected rats. No changes in wave rhythm or morphology were detected under baseline conditions. The PR and QaT intervals and QRS duration were significantly longer in both groups after ajmaline injection, at all periods studied. When the two groups were compared for relative variations, consistently and significantly higher alterations (p less than 0.05) were observed in the T. cruzi-infected group, except for the QaT interval at 180 seconds. However, the severe rhythm and ventricular conduction disturbances detected in 30% of the infected rats represented clear-cut discriminative alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ajmaline; Animals; Chagas Cardiomyopathy; Chagas Disease; Electrocardiography; Heart Rate; Male; Rats; Rats, Inbred Strains

The antiarrhythmic effects of verapamil, 17-monochloracetylajmaline, mexiletine and amiodarone were compared in 14 patients with chagasic myocarditis. Drugs and placebo were administered orally in the following order: placebo and verapamil, placebo and 17-monochloracetylajmaline, placebo and mexiletine (1 week each) and placebo and amiodarone (4 weeks each). A 24 hour ambulatory electrocardiographic recording was obtained after administration of each placebo and drug. Verapamil had no effect on the number of ventricular premature complexes, ventricular couplets and runs of ventricular tachycardia. 17-Monochloracetylajmaline did not reduce the number of ventricular premature complexes and ventricular couplets but caused a moderate reduction in runs of ventricular tachycardia. Mexiletine failed to significantly reduce ventricular premature complexes but caused a moderate decrease in both ventricular couplets and runs of ventricular tachycardia. Amiodarone was the only one of the four drugs that caused a substantial reduction of ventricular premature complexes (logarithmic mean 97.8%; p less than 0.001), total suppression of runs of ventricular tachycardia in 11 of 11 patients and suppression of ventricular couplets in 8 of 14 patients and a significant reduction in the remaining 6 patients. The much greater efficacy of amiodarone as compared with the two sodium channel modifiers (17-monochloracetylajmaline and mexiletine) and one calcium channel blocker (verapamil) suggests that its potent antiarrhythmic activity is probably related to other peculiar and still undefined electrophysiologic and pharmacologic properties.

Topics: Adult; Ajmaline; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Chagas Cardiomyopathy; Female; Humans; Male; Mexiletine; Middle Aged; Placebos; Propylamines; Verapamil

Topics: Ajmaline; Atropine; Blood Pressure; Bundle-Branch Block; Carotid Sinus; Chagas Cardiomyopathy; Electrocardiography; Exercise Test; Female; Humans; Male; Massage

Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.

Topics: Adolescent; Adult; Ajmaline; Bundle-Branch Block; Cardiac Complexes, Premature; Chagas Cardiomyopathy; Child; Electrocardiography; Female; Heart Block; Heart Conduction System; Humans; Male; Middle Aged

Topics: Adult; Aged; Ajmaline; Bundle-Branch Block; Chagas Cardiomyopathy; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis