Does Chagas' disease exist as an undiagnosed form of cardiomyopathy in the United States?
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Acute Disease↗
Biomedical subjects
J Milei
Publications and source records attributed to J Milei.
The hypertrophied myocardium and coronary disease. Structural changes in patients submitted to aortocoronary bypass surgery.
Seventeen patients with coronary disease submitted to myocardial revascularization were studied. Ten patients had a hypertrophied ventricle, and 7 had normal ventricular mass. Myocardial biopsies were obtained before ischemia and at the time of reperfusion and were assessed for: volume fraction of fibrous tissue, myocyte diameter, morphometric mitochondrial studies and ultrastructural changes. The volume fraction of fibrous tissue in patients with hypertrophied ventricle was 1.9 +/- 0.04, and in patients with normal ventricular mass was 0.9 +/- 0.01 (p less than 0.05). The diameter of the myocyte was 23 +/- 0.3 microns and 18 +/- 1.2 microns for patients with hypertrophied and normal ventricular mass, respectively (p less than 0.01). The value of volumetric density for pre-ischemia samples in patients with a hypertrophied ventricle was 23 +/- 2.2 and in patients with normal ventricular mass was 35 +/- 2.7 (p less than 0.02). Grades 3 and 4 of damaged mitochondria were significantly increased in reperfusion samples from patients with a hypertrophied ventricle compared to pre-ischemia samples. Collagen growth was increased in hypertrophied hearts which were also more sensitive to the ischemia/reperfusion mechanism.
Biopsy↗
Preservation of the myocardial collagen framework by human growth hormone in experimental infarctions and reduction in the incidence of ventricular aneurysms.
We administered human growth hormone to a group of rats with experimental myocardial infarctions, in order to observe its action on the connective tissue repair process and the consequent effect on postinfarction ventricular aneurysms. Myocardial connective tissue displays a complex layout around each myocyte and among neighboring ones. It has been shown to be highly vulnerable to acute coronary ischemia which affects its diverse components in accordance with a precise timetable. The ultimate consequence of ischemia on connective tissue is the disappearance of intermyocytic links and the collagen weave that surrounds each cell. Damage to this collagen framework of the heart is responsible for the final disarray of myocytes, with a parallel effect to the myocytolytic actions of ischemia within the very structure of each cell. Hence, the appearance of postinfarction ventricular aneurysms seems to be related to failure in normal repair processes resulting from maturation of new collagen tissue into the area of myocardial necrosis. It has been shown that, besides the well-known actions on chondrocytes, hypothalamic-hypophyseal human growth hormone and somatomedins activate the fibroblasts. Administration of human growth hormone resulted in a significant decrease in the incidence of ventricular aneurysms. Scanning electron microscopy showed a good preservation of connective tissue components of myocardium. A different histological pattern of necrosis resulted in the treated group.
Animals↗
Endomyocardial biopsies in chronic chagasic cardiomyopathy. Immunohistochemical and ultrastructural findings.
Mononuclear cellular infiltrates and extensive fibrosis, with or without apical ventricular aneurysms, are the usual morphological findings in chronic chagasic cardiomyopathy. These lesions are thought to be mediated by immune phenomena rather than by continuing parasitic invasion of the heart. In the present report, we correlated clinical, immunohistochemical and ultrastructural findings in 30 endomyocardial biopsies from patients with chronic chagasic cardiomyopathy. In 12 of these biopsies, immunocytochemical techniques were used to identify and count leukocytes (common leukocyte antigen, CLA), T lymphocytes (UCHL-1 antibody) and B lymphocytes (L-26 antibody). The biopsy specimens showed variable degrees of myocardial hypertrophy and mononuclear infiltrates. No tissue forms of trypanosomes were found. The endocardium averaged 24 +/- 12.6 microns (mean +/- SD) in thickness. The mean myocyte diameter was 20 +/- 7.33 microns. The hearts were severely fibrotic containing a mean of 24.1 +/- 12.8% of fibrous tissue (range 8.2-49%), mast cells were scarce. Mononuclear cell infiltrates were found in 25 of the 30 biopsies. In 12 biopsies, immunohistochemical studies showed that the majority of the lymphocytes were T lymphocytes and associated with necrotic or degenerating myocytes. 10 of the 12 biopsy samples showed 5 or more CLA-positive mononuclear cells/high power field. In these 10 patients, T and B lymphocytes represented 32 and 13% of the total mononuclear infiltrating cells, respectively. The remaining cells were monocytes and macrophages.
Adult↗
Effects of cloricromene on ischemia-reperfusion myocardial damage in the rabbit.
Cloricromene, a compound with several biological activities which suggest a therapeutic role in thrombosis or ischemic disease, has been studied for its effects on the extension of myocardial damage and the production of oxygen free radicals during periods of ischemia and reperfusion. In twenty rabbits the left anterior descending coronary artery (LAD) was occluded and cloricromene (3.6 micrograms/kg/min; n = 10) or placebo (n = 10) were continuously infused. After 50 min the artery was reopened and after 20 min of reperfusion a biopsy was obtained from the anterior wall of the heart in the LAD area and from the posterior wall (control myocardium) prior to sacrifice. Both samples were used for chemiluminescence measurement (free-radical production) and ultrastructural studies. In the placebo group all rabbits showed ST-segment changes during ischemia and reperfusion arrhythmias, while in the cloricromene group there were transient ST elevations in 4 animals which reverted at higher infusion rates of the drug. The chemiluminescence values were 18,017 +/- 1,956 and 8,583 +/- 918 cpm/mg protein (p < 0.001) in the anterior and posterior walls of the left ventricle, respectively, for the placebo group, and 7,767 +/- 992 and 8,333 +/- 832 cpm/mg protein (NS), respectively, for the cloricromene group. The ratio between the anterior and posterior wall was 2.27 +/- 0.37 for the placebo group versus 0.95 +/- 0.11 for the cloricromene group (p < 0.001). In ultrastructural studies, the anterior wall in the placebo group showed irreversible myocyte injury and infarction as well as mitochondrial damage. Samples from the cloricromene-treated group showed, in general, preservation of myocyte architecture or minor signs of injury. These results illustrate clearly the protective effect of cloricromene during damage induced by ischemia and reperfusion in the rabbit.
Animals↗
Reduction of myocardial damage by cloricromene during ischemia-reperfusion in the rabbit.
We studied the effect of cloricromene on myocardial damage during ischemia and reperfusion. The left anterior descending coronary artery was occluded in 20 rabbits and cloricromene (6.2 micrograms/kg/min) (n = 10) or placebo (n = 10) were continuously infused. After 10 minutes of occlusion, a first biopsy was obtained from the apex. After 30 minutes, the artery was reopened and after 10 minutes a second biopsy was taken. Both samples were used for chemiluminescence and electron microscopy. The group given placebo showed displacement of the ST segment throughout the ischemic period and arrhythmias during reperfusion; while, in the group given cloricromene, there were transient ST segment elevations in 5 animals, which reverted as the infusion was increased. The chemiluminescence values were 7100 +/- 1300 cpm/mg protein and 14900 +/- 2300 (p less than 0.01) for the first and second biopsies of the control group and 5900 +/- 900 and 6100 +/- 900 (NS) for the first and second biopsies of the cloricromene-treated group. In the group given placebo, the second biopsy showed early signs of irreversible myocyte injury and infarction, whereas samples from the group given cloricromene showed a preservation of myocyte architecture. During ischemia, the percentage of normal mitochondria was lower in the placebo group (p less than 0.0001); and, on reperfusion, the percentage of severely damaged mitochondria was increased in the placebo group (p less than 0.0001). The direct addition of cloricromene in vitro to myocardial homogenates did not reduce hydroperoxide-induced chemiluminescence.
Animals↗
Electrophysiologic-structural correlations in chagasic aneurysms causing malignant arrhythmias.
We studied the structure and ultrastructure of three chagasic aneurysms, the excision of which abolished malignant arrhythmias. Chronic recurrent ventricular tachycardia often occurs in patients with chagasic aneurysms, and ventricular mapping indicates that these arrhythmias originate in regions adjacent to those aneurysms. In our patients, ventricular tachycardia had been refractory to medical treatment. During surgery, epicardial and endocardial mapping showed abnormal potentials. Sutures were placed in the areas of resection, their sizes approximating those of earliest activation so that these sites could be identified. The myocardium showed chronic inflammatory reaction, myocytolysis and fibrosis. The presence of "islets" was common (normal, "early" damaged or "established" necrotic myocytes surrounded by fibrous tissue). The "early" lesions were predominant at the previously identified areas of arrhythmogenic activity. The ultrastructural studies showed hypertrophy of myocytes and partial or complete loss of myofibrils, swelling of mitochondria and disruption of mitochondrial cristae, accumulation of lipofuscin granules, and intracellular oedema. A most striking alteration was the thickening of the basement membranes of myocytes and vascular endothelial and smooth muscle cells. The interlaced fronts of respectively healthy (fast conducting) and "early" damaged (slow conducting) myocytes seen in serial sectioning produced an ideal configuration for reentry circuits. The final proof that the arrhythmias originated in these endocardial regions was their abolition by resection of the aneurysm.
Adult↗
Structural changes in implanted cardiac valvular bioprostheses constructed of glycerol-treated human dura mater.
Histological, scanning and transmission electron microscope studies were made of normal human dura mater and cardiac valvular bioprostheses made of glycerol-treated human dura mater recovered after having been implanted in the aortic position (8 patients) or the mitral position (1 patient) for periods up to 4 years. Human dura mater has two layers: an inner or meningeal layer and an outer or endosteal layer. The surface of the inner layer is smoother than that of the outer layer. Both layers are composed mainly of large, wavy collagen fibrils (which are thought to correspond to type I collagen) and are relatively poor in elastic fibers and proteoglycans. Small calcific deposits were found in normal dura from older patients. Changes occurring in dura mater bioprostheses within 2 days after implantation consisted mainly of small surface thrombi. Calcific nodules, degenerated collagen and evidence of penetration of erythrocytes and plasma proteins into the cusps were observed in bioprostheses that had failed after being in place for 1-4 years. The calcific deposits and the degenerated collagen appeared structurally similar to those in glutaraldehyde-treated porcine aortic valvular bioprostheses. However, collagen fibrils in the latter were smaller than those in dura mater. Platelet aggregates on the cuspal surfaces were much less numerous in dura mater bioprostheses than in porcine aortic valvular bioprostheses. It is postulated that this difference is a function of the size of the collagen fibrils in the bioprostheses and that this accounts for the very low incidence of clinically evident thromboembolism in patients with implanted dura mater valves.
Adolescent↗
Histopathology of specialized and ordinary myocardium and nerves in chronic Chagas disease, with a morphometric study of inflammation and fibrosis.
Chagas disease, in the chronic phase, is known to be characterized by cardiac failure, and/or arrhythmias. To assess the involvement of the conduction system and of the working myocardium, morphometric and immunohistochemistry studies have been carried out on 4 autoptic hearts of chronic chagasic myocardiopathy. The characterization of interstitial infiltrates was performed by lymphocyte immunophenotyping with immunocytochemical techniques. These infiltrates were more prominent in the working myocardium and in the left branch of the His bundle. The infiltrates consisted of about 50% of macrophages and 50% of T-lymphocytes. Mast cells would not play a role in the chronic stages of the disease. Eosinophils were present in no more than the 5% of the inflammation. The fibrosis, especially of the conducting system seems to be facilitated by an impaired lymphatic outflow, whereas the evidence of neuroganglionic involvement was variable.
Cardiomegaly↗
Morphometry of skeletal muscle involvement in mice infected or preimmunized with live attenuated Trypanosoma cruzi.
A morphometric study was undertaken in the quadriceps muscle of Swiss mice in order to assess the effects of immunization with attenuated T. cruzi upon tissue lesions. interfascicular lymphocytic infiltration, presence of amastigote nests, vascular lesions, degeneration and fibrosis were evaluated independently. Each of these alterations was drastically prevented in preimmunized animals. These results indicate that immunity against T. cruzi not only reduces circulating parasites but also clears most of the organic damage caused by infection.
Animals↗
Hemodynamic effects of chronic 4'epi-adriamycin administration.
Adriamycin (ADM) is an effective antineoplastic drug. However, the amount of ADM that can be administered must be limited because of the risk of developing a severe dose-dependent cardiomyopathy. 4'Epi-adriamycin (4'ADM) is a new anthracycline analog with similar antineoplastic properties as ADM, but with perhaps less cardiac toxicity. To determine myocardial performance after a chronic treatment with 4'ADM, we studied 17 patients (mean age 36.6 years) suffering from lymphomas by means of 24-hour ambulatory ECG, x-ray, M-mode echocardiogram, and rest-exercise gated radionuclide ventriculography (RNV), performed prior to and 2 months after the end of the treatment. Pretreatment and post-treatment shortening fractions, basal pretreatment and post-treatment ejection fractions, and postexercise pretreatment and post-treatment ejection fractions, were tested for correlation with individual 4'ADM doses and pretreatment with ADM. No association was noted among them, showing the lack of correlation between doses and impairment of ventricular performance. 4'ADM doses ranged from 400 to 1100, x 748 +/- 174 mg/m2; all noninvasive studies including RNV were normal. No correlation was found between 4'ADM doses and RNV (Pearson's correlation coefficient, p = ns). No deterioration of ventricular performance could be demonstrated. Conversely, the basal pretreatment ejection fraction changed from 56.17 +/- 7.6% to 61.52 +/- 8.3% in post-treatment (p less than 0.0001). Surprisingly, the post-exercise pretreatment ejection fraction also increased from 55.47 +/- 7.7% to 63.35 +/- 10% in post-treatment (p less than 0.03). The shortening fraction changed from 35.47 +/- 4.8% to 36.47 +/- 4.2% after 4'ADM treatment (ns). No impairment of cardiac function could be shown in patients previously treated with ADM or radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Myocardial damage induced by doxorubicins: hydroperoxide-initiated chemiluminescence and morphology.
Doxorubicin (1.2 mg/kg body weight) or 4'-epidoxorubicin (1.7 mg/kg body weight) was injected intravenously to rabbits twice a week during 7 to 8 weeks. Total doses were 17.9 +/- 0.2 mg and 24.4 +/- 0.3 mg, respectively. Heart, liver, muscle, and brain homogenates from treated and control animals were supplemented with 3 mM tert-butyl hydroperoxide and hydroperoxide-initiated chemiluminescence was measured. Heart homogenates from doxorubicin-treated rabbits showed an increased hydroperoxide-initiated chemiluminescence (77.2 +/- 3.9; expressed as cpm/mg protein X 10(-3]; whereas 4'-epidoxorubicin-treated rabbits did not exhibit changes (40.7 +/- 4.6) when both were compared with the untreated animals (41.3 +/- 3.0). Liver, muscle, and brain homogenates from doxorubicin and 4'-epidoxorubicin-treated animals showed a hydroperoxide-initiated chemiluminescence that was similar to the one from control animals. Microscopically, the total extent of the myocardial damage (as percentage of damaged myocytes) was markedly higher in the doxorubicin-treated rabbits (63.0 +/- 8.6) than in the 4'-epidoxorubicin-treated group (34.6 +/- 5.0); being both values higher than the one corresponding to control animals (8.0 +/- 1.1). The subendocardial areas of the septum and of the left ventricle were highly sensitive to doxorubicin damage. Hydroperoxide-initiated chemiluminescence of whole heart homogenate correlated statistically with the microscopic tissue damage in the subendocardial and intramural areas of the right ventricle. It is concluded that chronic administration of doxorubicins lead to oxidative stress of the myocardium and that 4'-epidoxorubicin produces less severe oxidative stress and less extensive myocardial damage than those provoked by lower doses of doxorubicin.
Animals↗
Immunohistochemical staining of lymphocytes for the reliable diagnosis of myocarditis in endomyocardial biopsies.
Interobserver variability in the interpretation of pathologic endomyocardial biopsies for detecting myocarditis has been widely reported. Thus, conflicting reports about the therapeutic benefit of immunosuppressive treatment in myocarditis may be due to differences in the interpretation of the biopsy findings. In doubtful cases, scattered interstitial cells may be present between myocytes and can be misinterpreted as true lymphocytes. In our study, a further characterization of interstitial cells in endomyocardial biopsies previously diagnosed as showing 'myocarditis' was performed by lymphocyte immunophenotyping with immunocytochemical techniques for membrane and cytoplasmic antigens. Common leukocyte antigen (CLA), kappa and lambda light immunoglobulin chains and T lymphocyte antigens were made visible by an indirect immunoperoxidase technique. A previous diagnosis of 'myocarditis' had been established histologically in 27 patients by the presence of an inflammatory cell infiltrate associated with focal acute cellular damage. These specimens were selected for further study using an immunoperoxidase technique. The number of negative and positive mononuclear cells for each marker was counted on all fields at a magnification of X 400. These numbers were correlated with the extent of interstitial fibrosis and/or myocyte damage on each sample. According to previous studies, 5.0 lymphocytes/high-power field were considered as the lower limit of myocarditis if they were associated with myocyte injury. From the 27 samples previously diagnosed histologically as 'myocarditis' only 14 showed 5 or more CLA-positive mononuclear cells/X 400 field. In 6 out of 8 selected cases having less than 5 CLA-positive cells, no T-antigen-positive cells could be detected. The remaining samples showed T lymphocytes localized in acute infiltrated areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Bivalent effects of human growth hormone in experimental myocardial infarcts. Protective when administered alone and aggravating when combined with beta blockers.
Human growth hormone (hGH) administered alone revealed itself as a useful drug to prevent ventricular aneurysm formation in experimental myocardial infarctions in rats and is also able to diminish and change the usually expected pattern of wall necrosis. A protective action on the collagen framework of myocytes has been confirmed as one of the main causes responsible for the above mentioned findings. There are other positive metabolic actions on the myocardial cell although not completely known yet. These actions are revealed by an atypical picture of infarction which appears regionally reduced and with a patchy intracellular distribution. In an opposite fashion, when hGH was administered together with beta blockers, a rapid and extensive deleterious action occurred at the ventricular wall, a very high incidence of ventricular aneurysms and an increased extension of myocardial infarcts were the most outstanding features. The histologic picture in this series resembles that of a rapidly evolving diabetic cardiomyopathy.
Adrenergic beta-Antagonists↗
Effect of supplementing cardioplegic solution with deferoxamine on reperfused human myocardium.
Fourteen randomized patients undergoing myocardial revascularization were divided into group A standard hypothermic cardioplegic solution) and group B (the same cardioplegic solution supplemented with deferoxamine 1000 mg/L). In all patients myocardial biopsy specimens were obtained before ischemia and during reperfusion and were assessed for chemiluminescence (to indirectly determine oxygen-free radical activity) and for electron microscopic studies. Chemiluminescence in group A showed a photoemission of 36.5 +/- 1.5 cpm/mg protein X10(-3) for the preischemia samples and 72 +/- 5.7 cpm/mg protein X10(-3) for the reperfusion samples (p less than 0.01). In the patients who received deferoxime (group B), values for chemiluminescence for preischemia and reperfusion samples were not significantly different. Electron microscopic studies showed a significant increase in grade 4 (severely damaged) mitochondria in reperfusion biopsy specimens from both groups as compared with preischemia samples. However, reperfusion samples from group B showed a better preservation of myocardial cells with marked reduction of grade 4 (severely damaged) mitochondria. These results support the hypothesis that oxygen-free radicals are responsible in part for the production of reperfusion injury in the human heart. They suggest that this mechanism may be at least partially controlled by adding an iron chelating agent such as deferoxime.
Cardioplegic Solutions↗
Reduction of reperfusion injury with mannitol cardioplegia.
Forty consecutive patients undergoing myocardial revascularization were divided into two equal groups: group 1 received standard cardioplegic solution, and group 2 received a solution containing mannitol, 59.8 mmol/L. In 6 patients in each group, myocardial biopsies were done before ischemia and at the time of reperfusion. Samples were assessed by chemiluminescence to determine oxidative stress and by electron microscopic studies. A significant reduction in atrial arrhythmias was observed in the mannitol group. Chemiluminescence in group 1 showed a photoemission of 37.6 +/- 3.5 cpm/mg of protein x 10(-3) for the preischemia samples and 74.8 +/- 16 cpm/mg of protein x 10(-3) for the reperfusion samples (p less than 0.001). In group 2, the values for chemiluminescence were 37.7 +/- 3.4 cpm/mg of protein x 10(-3) and 40 +/- 6.1 cpm/mg of protein x 10(-3), respectively (p = not significant). Electron microscopic studies showed, for group 1, increased grades of damaged mitochondria in the reperfusion biopsy specimens compared with the preischemia biopsy specimens (p less than 0.01). In group 2, differences for damaged mitochondria were not significant. These results support the hypothesis that mannitol reperfusate significantly reduces myocardial damage in patients undergoing open heart procedures. They also suggest that this protective effect may be in part secondary to the antioxidant property of mannitol, although other mechanisms may have accounted for or contributed to the improved outcome after ischemia.
Biopsy↗
Ketanserin in the treatment of essential hypertension. A double blind trial against metoprolol followed by one-year open treatment.
The present study was designed to compare the antihypertensive potencies of ketanserin and metoprolol in a double-blind trial and to study ketanserin long-term efficacy in a one-year open trial, plain or combined with metoprolol, according to diastolic blood pressure (DBP) normalization. Thirty-four patients were randomly assigned to two groups, one (n = 17) received ketanserin, 80 mg/day, and the other, (n = 17) metoprolol, 200 mg/day. After 3 mo. double blind treatment, all patients received plain ketanserin, or combined with metoprolol if ketanserin failed to normalize DBP. A significant effect was demonstrated after 3 mo. double blind treatment, for both drugs, in both standing and supine DBP (p less than 0.001). In the one-year follow-up, all patients received ketanserin and were divided in: I (n = 15) previously treated with the same drug; II (n = 2) plus metoprolol, in whom ketanserin had failed to decrease DBP; and III (n = 15) previously treated with metoprolol. In group I the blood pressure lowering effect of ketanserin remained constant during the one-year follow-up. In group II a trend in the decrease of parameters was observed. In group III, supine DBP diminished from 92.5 +/- 2 mmHg during treatment with metoprolol to 86.0 +/- 2 at 12 mo., after treatment with ketanserin (p less than 0.05). In groups I and III, 24/30 of patients normalized their DBP during one-year ketanserin open treatment. Ketanserin appears as a new alternative in the treatment of mild and moderate essential hypertension.
Adult↗
Myocardial involvement in Cavia porcellus naturally infected with Trypanosoma cruzi.
This paper describes the myocardial involvement analyzed by histopathological examination in rural Cavia porcellus during natural T. cruzi infection. Four Cavia porcellus of both sexes were bred in a house free of Triatoma infestans. In contrast, four animals were born and lived in a rural yard colonized by T. infestans. Autopsies were performed at 6-9 months of age, in animals weighing 550 to 750 grams. The naturally infected Cavia porcellus presented moderate and severe lymphocyte and plasmocyte infiltrates, focally or diffusedly distributed. Replacement of myocytes both in atria and ventricles was often found and consisted of loose or dense connective tissue infiltration. Regarding the conducting system, polymorphonuclear cell infiltrates were observed in the A-V node and in the left bundle branch. Uninfected Cavia porcellus did not show these lesions. Typical chagasic cysts were not found in the naturally infected Cavia porcellus hearts. Parasitism was not observed in the skeletal muscles. It is concluded that naturally infected Cavia porcellus develop consistent lesions similar to those described in human chronic chagasic myocardiopathy. The high susceptibility of naturally infected Cavia porcellus must be taken into account when these animals are used in studies regarding chronic chagasic myocardiopathy.
Animals↗