Effects of long term metoprolol administration on the electrocardiogram of rats infected with T cruzi.

STUDY OBJECTIVE: The aim of the study was to evaluate the role of beta receptor antagonists in the evolution of experimental Chagas' disease. DESIGN: Rats were infected with T cruzi, 2000 parasites.g-1 body weight, soon after weaning. One group was then given metoprolol, 100 mg.kg-1.d-1, in drinking water. A comparison group received no metoprolol. Two control groups of non-infected rats were also studied, one with and one without metoprolol in the same dose. SUBJECTS: Adult male albino rats were used: 144 were infected with T cruzi and received metoprolol (group IM), 137 were infected and received no metoprolol (group IW), 46 non-infected rats received metoprolol (group CM), and 43 non-infected rats did not receive metoprolol (group CW). MEASUREMENTS and main results--30 d after infection, resting ECG was performed in all surviving rats. (There were 63 deaths in the infected groups and none in the non-infected groups.) Abnormal ECG was found in 20/81 infected rats in group IM and in 30/74 in group IW (p less than 0.05). No ECG changes were found in the non-infected rats. Of rats in group IM with normal resting ECG, 31 continued to take metoprolol (group IMNM), while 30 similar rats did not (group IMNW); in group IM with abnormal ECG, 10 rats continued to take metoprolol (group IMAM), while 10 similar rats did not (group IMAW). Of rats in group IW with normal ECG, 22 were started on metoprolol (group IWNM), while 22 similar rats were not (group IWNW); in group IW with abnormal ECG, 15 rats were started on metoprolol (group IWAM), while 15 similar rats did not (group IWAW). After 120 d and 300 d infection there were no differences in mortality rate and Ajmaline test in any of the matched groups (IMNM X IMNW; IMAM X IMAW; IWNM X IWNW; IWAM X IWAW). After 120 d there was no difference in ECG between the groups, but after 300 d there was a decrease in abnormal ECG in group IWAM (IWAM v IWAW, 0/12 v 5/12, p less than 0.05). No histological differences were found. CONCLUSIONS: Metoprolol decreases the proportion of rats with abnormal resting ECG in both the acute and the chronic stage of T cruzi infection.

Megacolon in rats.

Four months of sigmoid colon intrinsic denervation of young male Wistar rats resulted in typical megacolon. Average 46.0% denervation of the Auerbach plexus was obtained by serosal application of benzalkonium chloride (0.2% v/v). Denervation was assessed by ganglion cell counts in a 480-nm extension of the treated segment. Increased thickness of the megacolon wall was due to muscle hypertrophy (+117.4%) and mucosal hyperplasia (+53.9%) as shown by morphometry. The potential usefulness of this experimental model is emphasized.

The ajmaline test as a method to disclose latent experimental Chagas' heart disease.

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.

Effect of chemical ablation of myenteric neurones on intestinal cell proliferation.

The duodenum or descending colon of male Wistar rats (average weight 60 g) was treated by a serosal application of a 0.2% solution of benzalkonium chloride (BAC) for 30 min. Control animals were treated with 0.9% (physiological) saline. The rats were allocated to four groups: Group DC (N = 8) in which the duodenum was treated with physiological saline; Group DB (N = 8) in which the duodenum was treated with BAC; Group CC (N = 7) in which the descending colon was treated with physiological saline and Group CB (N = 7) in which the descending colon was treated with BAC. After treatment, the animals were followed up for 5 months. At the end of the experiment, the animals were injected intraperitoneally with vincristine sulphate before sacrifice. Three segments were removed from the duodenum and descending colon for neuronal counting, catecholamine and serotonin measurements and morphokinetic studies of the epithelium. The following results were obtained: (1) there was a significant reduction in neurone number in the myenteric plexus of segments treated with BAC; (2) in the denervated intestinal segments, catecholamine levels were unchanged whereas serotonin levels were increased; (3) epithelial hyperplasia was observed in the denervated duodenum and descending colon; and (4) crypt cell production rate in the duodenum was similar in groups DC and DB but was significantly increased in the descending colon in group CB as compared with controls (CC). The present findings indicate that selective myenteric neuronal denervation caused by benzalkonium chloride plays a causative role in the hyperplasia and crypt cell production rate of the intestinal epithelium (duodenum and descending colon). These changes are probably induced by functional imbalance by the surviving neuronal elements in the gut, implicating neurotransmitters such as acetylcholine, noradrenaline, serotonin, somatostatin and vasoactive intestinal peptide.

The usefulness of the resting electrocardiogram for characterizing acute Chagas' heart disease in the rat.

The present experiment was undertaken to characterize the resting electrocardiogram of rats in the acute stage of experimental T. cruzi infection. One-hundred-and-eighty-seven newly-weaned male albino rats were infected intraperitoneally with 1000 parasites/g body weight. Thirty-two similar but non-infected rats served as controls. Groups of eight randomly chosen rats were killed on day 8, and on days 15, 18, 22, 25 and 29 after infection. Groups of 8 control rats were killed on days 8, 15 and 22. Electrocardiographic changes were observed in 25 of 48 (52%) infected rats. P wave abnormalities indicating atrial chamber dilatation, QRS axis deviation, QRS complex changes compatible with left ventricular hypertrophy or myocardial damage, increased PR interval and ventricular repolarization alteration were detected in 24, 27, 18, 10, and 6% of infected rats, respectively. A mononuclear cell infiltrate and pseudocysts of amastigote forms of T. cruzi were found in 91, and 56% of infected animals, respectively. The sensitivity and the positive predictive value of the electrocardiographic changes were 66, 91, and 96%, respectively. Thus, the resting electrocardiogram is a reliable method for detecting myocardial lesions in the rat with acute Chagas' heart disease.

Ability of the electrocardiogram to detect myocardial lesions in isoproterenol induced rat cardiomyopathy.

Resting electrocardiograms were recorded in 18 male adult rats injected subcutaneously with two doses of isoproterenol (200 mg.kg-1 body weight) 10 days before the animals were submitted to the ajmaline test (1 mg.kg-1 body weight iv). After the ajmaline test all rats were killed and the hearts examined histologically. Electrocardiographic changes were detected at rest in 72% of the isoproterenol injected rats: pathological Q waves, lengthening of the QRS complex, and QRS abnormality were found in 50%, 44%, and 44% of these animals respectively. Ajmaline induced similar changes in both control and isoproterenol treated rats (P wave enlargement (p less than 0.01 and p less than 0.001 respectively), increased PR interval (p less than 0.003 and p less than 0.001 respectively), and increased QaT interval (p less than 0.001 in both groups]. However, ajmaline caused an increase in heart rate only in isoproterenol treated rats (p less than 0.05). A pronounced increase in PR interval, not observed in control rats, was detected in one of five isoproterenol injected rats with a normal resting ECG but showing microscopical cardiac lesions. Apical aneurysm of the left ventricle was found in 16% of isoproterenol injected rats. A mononuclear inflammatory reaction was observed in 13 (72%) of the isoproterenol injected rats and was multifocal in at least three regions of the myocardium in six (46%) and disseminated throughout the myocardium in seven (53%) of these animals. When the electrocardiographic and pathological findings were compared, the ECG changes were found to have a 91% sensitivity, 83% specificity, and 91% positive predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic changes in T. cruzi-infected rats after the ajmaline test.

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.