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Charles Mady

Publications and source records attributed to Charles Mady.

52 records · Page 3Linked to original sources
PubMed2004

Echocardiographic assessment of global ventricular function using the myocardial performance index in rats with hypertrophy.

Myocardial hypertrophy is the hallmark of chronic pressure overload and the myocardial performance index (MPI) is an easily recordable measurement of Doppler time intervals. In this study, the utility of using MPI to assess the progression of hypertrophy in the aortic-banded rat model was evaluated. Male Wistar rats (70-90 g) underwent ascending aorta constriction (n = 4) or a sham operation (n = 5). High-resolution echocardiography was performed 4, 7, 10, and 12 weeks after the surgery. Over this follow-up interval, animals in the aortic-banded group demonstrated an increase in their mean left ventricular (LV) mass and MPI compared with controls. MPI reflects ventricular performance in small animals with LV hypertrophy, showing alterations early after aorta constriction.

Animals↗
PubMed2004

Assessment of diastolic function in endomyocardial fibrosis: value of flow propagation velocity.

Endomyocardial fibrosis is manifested mainly by diastolic heart failure. However, diastolic function has not been well characterized in this disease. The aim of this study was to characterize left ventricular (LV) diastolic function in endomyocardial fibrosis (EMF) by echocardiography. Eighteen patients with LV EMF and 18 healthy subjects were studied. Cardiac volumes and ejection fraction were assessed by Simpson's method. Pulsed-wave Doppler was used to obtain mitral and pulmonary venous flow velocities and grade diastolic function. Pulsed-wave tissue Doppler imaging velocities along the septal side of mitral annulus, flow propagation velocity (Vp) of the early diastolic mitral inflow, and myocardial performance index were obtained. According to this grading method, four patients with normal diastolic function, five with impaired relaxation, five with pseudonormal, and four with a restrictive pattern were found. A positive correlation of these diastolic function grades and NYHA functional class was found (r = 0.66, P = 0.003). By "stepwise" logistic regression the best index that discriminated EMF patients from controls was Vp. The probability of occurrence of EMF = exp(7.9288 - 0.1366 Vp)/1 + exp(7.9288 - 0.1366 Vp). A wide range of diastolic function grades is found in patients with EMF and these correlated with functional class. Delayed myocardium relaxation, as reflected by altered Vp, was a frequent finding, making Vp the most useful index to discriminate EMF patients.

Adult↗
PubMed2003

Increased plasma levels of tumor necrosis factor-alpha in asymptomatic/"indeterminate" and Chagas disease cardiomyopathy patients.

We compared plasma tumor necrosis factor-alpha (TNF-alpha) levels among asymptomatic/"indeterminate" Chagas disease patients (ASY) and patients across the clinical spectrum of chronic Chagas disease cardiomyopathy (CCC). Idiopathic dilated cardiomyopathy (DCM) patients and normal controls (NC) were included as controls. ASY Chagas disease patients had significantly higher plasma TNF-alpha levels than NC. TNF-alpha levels among severe CCC patients with significant left ventricular (LV) dysfunction were similar to those of DCM patients, showing average 2-fold higher levels than CCC patients without LV dysfunction and ASY patients, and 8-fold higher levels than NC. In Chagas disease, chronic TNF-a production prior to heart failure may play a role in CCC progression.

Adult↗
PubMed2003

The Syrian hamster as a model for the dilated cardiomyopathy of Chagas' disease: a quantitative echocardiographical and histopathological analysis.

Chronic Chagas' disease cardiomyopathy (CCC) is caused by the protozoan Trypanosoma cruzi, and it affects 30% of the 16-18 million people infected in Latin America. A good rodent model that develops a dilated cardiomyopathy closely resembling human CCC after T. cruzi infection is still needed. We compared the cardiomyopathy developed by T. cruzi-infected Syrian hamsters with human Chagas' disease cardiomyopathy using quantitative methods. Female hamsters were infected with 3.5 x 10(4) (G1, n = 10) or 10(5) (G2, n = 10) T. cruzi Y strain blood trypomastigotes. Control animals (C, n = 10) were injected with saline solution. Cardiac function was assessed by echocardiography at 4, 8 and 12 months post-infection. Heart sections were submitted to histopathological/morphometric analysis 12 months post-infection. At this time, ventricular dysfunction and diffuse or multi-focal myocarditis were observed in 91% and 100% of G1 and G2 infected groups, respectively. Median interstitial collagen volumes in groups C, G1 and G2 were 1.2%, 1.9% and 3.9%, respectively, and were significantly higher in group G2 than in group C. Among infected animals, myocarditis showed a positive correlation with interstitial fibrosis. Deaths in the chronic phase (8-12 months post-infection) were more frequent among G2 than G1, and were associated with macroscopic ventricular dilation, severe myocarditis and increased fibrosis values, along with an earlier onset of ventricular dysfunction. The T. cruzi chronically infected Syrian hamster develops a cardiomyopathy which resembles human Chagas' disease cardiomyopathy, and might be an adequate tool to investigate pathogenic mechanisms of this disease and to search for novel therapeutic strategies.

Animals↗
PubMed2003

Noninvasive assessment of hemodynamic parameters in experimental stenosis of the ascending aorta.

We sought to noninvasively evaluate left ventricular (LV) function after cardiac hypertrophy induced by experimental stenosis of the ascending aorta. Male Wistar rats (70-90 g) underwent ascending aorta constriction by the surgical placement of a titanium clip (n=5) or sham operation (n=6). High-resolution bidimensional, pulsed-wave Doppler (PWD) and pulsed-wave tissue Doppler imaging (TDI) were performed 22 weeks after surgery. PWD was used to obtain mitral flow velocities, and TDI was used to obtain velocities along the septal mitral annulus and LV posterior wall. Clip placement produced myocardial hypertrophy with decreased systolic myocardial peak velocity in both the long and short axes. Increased myocardial mass, that is, posterior wall and septal thickness, was indicative of ventricular remodeling. Diastolic dysfunction was observed, with an increased early to late ratio of mitral velocities and increased left atrium dimension, consistent with a left ventricular restrictive filling pattern.

Animals↗
PubMed2003

Endothelins and myocardial fibrosis.

BACKGROUND: Endothelins are associated with cardiac remodeling. These peptides are the most powerful vasoconstrictor described-whether this remodeling is a direct effect of this hormone or indirect response to a relative ischemia promoted by vasoconstrictor effect. We evaluated the role of endothelin upon myocardial fibrosis despite of its hemodynamic effects and the benefits of its antagonism. METHODS AND RESULTS: We used 40 Wistar rats: control, sham operated, rats had undergone myocardial infarction (MI) and MI rats treated with SB209670 which is an ET(A)/ET(B) endothelin antagonist. We evaluated tail systolic blood pressure (BP) and left ventricular end diastolic pressure (LVED) before surgery, just after, and at the end of the study. Remodeling was studied based on interstitial collagen and MI size by an image system analysis. BP decreased in MI groups after surgery, but did not differ between treated and untreated animals. LVED had increased levels in MI groups after surgery and did not differ between them. However, ICVF had an increase in MI group but significantly less in MI+SB209670. MI size was similar in both groups. CONCLUSIONS: Endothelin may have a pivotal role in the myocardial fibrosis by direct stimulation of collagen accumulation despite of its hemodynamic effects.

Animals↗
PubMed2003

Cardiac remodeling in patients with systemic sclerosis with no signs or symptoms of heart failure: an endomyocardial biopsy study.

BACKGROUND: Systemic sclerosis (SSc) is a disease characterized by the fibrosis of the skin and internal organs. The nature and functional significance of myocardial damage is controversial. Systematic endomyocardial biopsy in this disease has not yet been performed. METHODS: The hypothesis that increased myocardial fibrous tissue deposition occurs in patients with systemic sclerosis with no signs or symptoms of heart failure and normal left systolic ventricle function was tested in 16 SSc patients and 10 controls. Endomyocardial biopsy specimens were obtained from the right ventricular septum in SSc patients. Myocardial specimens were obtained from the same area in controls. Masson's trichrome staining was used for collagen fiber identification. Interstitial (ICVF) and perivascular collagen volume fraction (PCVF) was quantified by videomorphometry. There was a significant increase in the ICVF in patients with SSc compared with the controls, in spite of normal systolic left ventricular function. However, it was not observed in the PCVF. CONCLUSIONS: It is possible to identify cardiac remodeling, characterized by myocardial fibrosis deposits, particularly within the interstitium in SSc patients before the any signs or symptoms of heart failure appear.

Adult↗
PubMed2002

Coronary flow velocity reserve in hypertensive patients with left ventricular systolic dysfunction.

BACKGROUND: Hypertensive microvascular disease is speculated to be a limiting factor for the ability of left ventricular (LV) hypertrophy to maintain LV systolic function in systemic hypertension. The role of coronary reserve, which may be affected by microvascular disease, remains uncertain in the pathophysiology of hypertensive heart disease. HYPOTHESIS: A progressive impairment of coronary flow velocity reserve (CFVR) according to the presence and severity of LV systolic dysfunction is anticipated to occur in hypertension. METHODS: According to the absence or presence of LV dysfunction (LV fractional shortening - FS% < 30), two groups of hypertensive patients were investigated: HP1 (n = 9, FS% = 36+/-6) and HP2 (n = 13, FS% = 18+/-6). Eight normal subjects (NL) served as controls (LVFS% = 35+/-3). Doppler blood flow velocity was obtained from the left anterior descending coronary artery using transesophageal echocardiography before, and during 6-min continuous adenosine infusion (140 microg x kg(-1) x min(-1) intravenous). The CFVR was calculated as the ratio of maximal to baseline peak diastolic flow velocities. RESULTS: The comparison among NL, HP1, and HP2 groups showed statistically different (p < 0.05) mass index (101+/-18, 172+/-46, and 257+/-54 g x m(-2)), end-systolic wall stress (76.9+/-14.4, 78.4+/-23.9, and 174.5+/-43.0 10(3) x dyn x cm(-2)), and CFVR (3.5+/-0.6, 3.2+/-0.4, and 2.6+/-0.8), respectively. The CFVR correlated significantly and directly with LVFS% (r = 0.40) and correlated inversely with both mass index (r = -0.54) and end-systolic stress (r = -0.40). CONCLUSIONS: These results indicate that CFVR impairment is weakly related to LV dysfunction in hypertension.

Adult↗
PubMed2002

Treatment of acromegaly improves myocardial abnormalities.

BACKGROUND: Treatment for acromegaly decreases left ventricular (LV) mass, but it is not clear whether diastolic dysfunction is also reversible. With Doppler echocardiography, before and after effective therapy, we assessed the LV morphology and function of patients with acromegaly who were free of complications. METHODS: In 15 patients with active acromegaly (age range, 33.4 +/- 9.3 years), we compared LV Doppler echocardiographic indices, before and after transsphenoidal surgery or radiotherapy or before and after both procedures, noting a significant drop in plasma levels of growth hormone (<2.0 ng/mL after oral glucose tolerance testing). Patients did not have arterial hypertension, diabetes mellitus, thyroid dysfunction, or coronary artery disease. Occasionally, in this series, patients had no symptoms of heart failure, and patients who underwent treatment with somatostatin analog drugs were not included because they did not have a significant hormonal drop. The follow-up period after hormonal control was 2.7 +/- 1.7 years. We also studied 15 healthy control subjects matched for age, sex, and body surface area. RESULTS: Patients with acromegaly compared with healthy control subjects had increased LV mass index, relative wall thickness, and deteriorated diastolic function. After therapy, most of the abnormalities improved: LV mass index (104 +/- 21 g/m(2) x 87 +/- 21 g/m(2); P <.01), LV relative wall thickness (0.40 +/- 0.06 x 0.35 +/- 0.04; P <.01), proto/telediastolic transmitral peak flow velocity ratio (1.17 +/- 0.33 x 1.49 +/- 0.34; P <.001), and isovolumetric relaxation period (126 +/- 18 ms x 113 +/- 13 ms; P <.05). CONCLUSION: Treatment of acromegaly in patients without clinical heart failure improves both LV morphology and diastolic function. Avoidance of progression to more advanced forms of acromegalic cardiomyopathy should be possible.

Acromegaly↗
PubMed2002

Clinical meaning of ascites in patients with endomyocardial fibrosis.

OBJECTIVE: To evaluate the clinical meaning of ascites and the main features of patients with ascites and endomyocardial fibrosis. METHODS: We studied 166 patients with endomyocardial fibrosis (mean age 37 years, 114 women) treated over the last 20 years. Ventriculography findings, surgery or necropsy confirmed the diagnosis in all patients. Most patients belonged to New York Heart Association Functional Class III/IV (134, 83.7%). Eighty-one (50.6%) had biventricular, 28 (17.5%) had right ventricular, and 51 (31.8%) had left ventricular involvement. During follow-up, 56 patients died. RESULTS: Ascites was present in 67 (41.8%) patients, and right ventricular involvement was present in 59 (88%). In the comparison between patients with or without ascites, those with ascites had higher mortality (49.2% and 24.7%, respectively). Patients with ascites had a higher incidence of edema (95% vs. 43%), hepatomegaly (5.8cm vs. 4.1cm), mean right atrium pressure (19.3 vs. 12mmHg), and final right ventricle diastolic pressure (18.7 vs. 12.9mmHg). Also, patients with ascites had a longer history of illness (5.1 and 3.9 years, respectively) and had atrial fibrillation more frequently (44.7% vs. 30.1%). CONCLUSION: Ascites was observed in less than 50% of cases of endomyocardial fibrosis and was associated with greater involvement of the right ventricle and with a longer duration of the disease, thus being a characteristic of a worse prognosis.

Adolescent↗
PubMed2002

Mitral valve replacement and remodeling of the left ventricle in dilated cardiomyopathy with mitral regurgitation: initial results.

OBJECTIVE: This study evaluated the effects of a new method of mitral valve replacement on left ventricular (LV) remodeling and heart failure functional class. METHODS: Eight patients (6 men) with severe mitral regurgitation from end-stage dilated cardiomyopathy underwent surgery. Five patients were in functional class (FC) IV, 2 were in FC III and 1 was in FC III/IV. Age ranged from 33 to 63 years. Both the anterior and posterior leaflets of the mitral valve were divided into hemileaflets. The resultant 4 pedicles were displaced under traction toward the left atrium and anchored between the mitral annulus and an implanted valvular prosthesis. The beating heart facilitated ideal chordae tendineae positioning. RESULTS: All patients survived and were discharged from the hospital. After a mean follow-up period of 6.5 months (1-12 m), 5 patients were in FC I; 2 in FC I/II; and 1 in FC II. The preoperative ejection fraction ranged from 19% to 30% (mean: 25.7 +/- 3.4 %), and the postoperative ejection fraction ranged from 21% to 40% (mean: 31.1 +/- 5.8%). Doppler echocardiography showed evidence of LV remodeling in 4 patients, including lateral wall changes and a tendency of the LV cavity to return to its elliptical shape. CONCLUSION: This technique of mitral valve replacement, involving new positioning of the chordae tendineae, allowed LV remodeling and improvement in FC during this brief follow-up period.

Adult↗
PubMed2002

Pregnancy and peripartum cardiomyopathy. A comparative and prospective study.

OBJECTIVE: To assess pregnancy outcome in women with peripartum cardiomyopathy and to compare it with idiopathic cardiomyopathy. METHODS: Twenty-six pregnant women, aged 28.4+/-6.1 years, with dilated cardiomyopathy were followed. Eighteen patients had peripartum cardiomyopathy [11 with persistent left ventricular systolic dysfunction (EF=45.2+/-2) and 7 with recovered ventricular function (EF=62.3+/-3.6)]. The 8 remaining patients had idiopathic cardiomyopathy (EF= 43.5+/-4.1). During the prenatal period, limited physical activity and a low-sodium diet were recommended, and hospitalization was recommended when complications occurred. RESULTS: Of the 26 patients, 11 (42.3%) had a normal delivery; 9(35.5%) had cardiac complications, 6 (22.2%) had obstetric complications. Two patients (7.7%) died. Two preterm pregnancies occurred, with 26 health newborns (2 sets of twins). Two miscarriages took place. The cardiac complication rate during pregnancy was lower (p<0.009) in the peripartum cardiomyopathy group without ventricular dysfunction and greater (p=0.01) in the idiopathic group when compared with the peripartum group with ventricular dysfunction. Changes in left ventricular ejection fraction were not observed (p<0.05) in the postpartum period, when compared with that during pregnancy in the 3 groups. CONCLUSION: Pregnancy in patients with dilated cardiomyopathy is associated with maternal morbidity. Left ventricular function is a prognostic factor and must be the most parameter when counseling patients with peripartum cardiomyopathy about a new pregnancy.

Adolescent↗
PubMedDate not supplied

T cell epitope characterization in tandemly repetitive Trypanosoma cruzi B13 protein.

Proteins containing tandemly repetitive sequences are present in several immunodominant protein antigens in pathogenic protozoan parasites. The tandemly repetitive Trypanosoma cruzi B13 protein is recognized by IgG antibodies from 98% of Chagas' disease patients. Little is known about the molecular mechanisms that lead to the immunodominance of the repeated sequences, and there is limited information on T cell epitopes in such repetitive antigens. We finely characterized the T cell recognition of the tandemly repetitive, degenerate B13 protein by T cell lines, clones and PBMC from Chagas' disease cardiomyopathy (CCC), asymptomatic T. cruzi infected (ASY) and non-infected individuals (N). PBMC proliferative responses to recombinant B13 protein were restricted to individuals bearing HLA-DQA1*0501(DQ7), -DR1, and -DR2; B13 peptides bound to the same HLA molecules in binding assays. The HLA-DQ7-restricted minimal T cell epitope [FGQAAAG(D/E)KP] was identified with an overlapping combinatorial peptide library including all B13 sequence variants in T. cruzi Y strain B13 protein; the underlined small residues GQA were the major HLA contact residues. Among natural B13 15-mer variant peptides, molecular modeling showed that several variant positions were solvent (TCR)-exposed, and substitutions at exposed positions abolished recognition. While natural B13 variant peptide S15.9 seems to be the immunodominant epitope for Chagas' disease patients, S15.4 was preferentially recognized by CCC rather than ASY patients, which may be pathogenically relevant. This is the first thorough characterization of T cell epitopes of a tandemly repetitive protozoan antigen and may suggest a role for T cell help in the immunodominance of protozoan repetitive antigens.

Amino Acid Sequence↗
PubMedDate not supplied

Endothelial function is preserved in Chagas' heart disease patients without heart failure.

Endothelium may be damaged, especially at the coronary microcirculation, in animal models of Chagas' disease by several mechanisms. Endothelial dysfunction has been reported in chronic Chagas' heart disease patients with heart failure. Nevertheless, peripheral endothelial function has never been studied in patients with Chagas' heart disease without heart failure and other conditions that could per se alter the endothelial function. Endothelial function was evaluated in 9 patients with Chagas' heart disease (44.8 +/- 1.5 years, 5 females, left ventricular ejection fraction > or = 60%) and 10 healthy matched controls (38.6 +/- 5.5 years, 5 females). Extreme caution was exercised to select patients with no other conditions that could per se alter the endothelial function. Forearm blood flow was measured at baseline and during intra-brachial artery infusion of crescent doses of acetylcholine (0.75, 5, and 15 microg/100 mL tissue/min) and nitroprusside (1, 2, and 4 microg/ 100 mL tissue/min), an endothelium-dependent and an endothelium-independent vasoactive drug, respectively. At baseline, blood pressure and heart rate (continuously recorded with Finapress) and the forearm blood flow were similar in both groups. Acetylcholine (ACh) and sodium nitroprusside (SNP) caused significant and similar dose-dependent increases in forearm blood flow of all subjects: maximum ACh response of 24.8 versus 23.7, and maximum SNP response 24.4 versus 23.7 mL/100 mL tissue/min, respectively, for control and chagasic Groups. No significant systemic hemodynamic changes were observed during the intra-arterial infusion of the drugs. The authors conclude that the peripheral endothelial function is preserved in Chagas' heart disease patients without heart failure.

Acetylcholine↗