Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas' disease: assessment by dobutamine stress echocardiography

OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium. BACKGROUND: Segmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas' heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas' disease. In addition, chagasic sera may contain autoantibodies against human beta-adrenergic receptors. METHODS: Two groups of patients with Chagas' disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation. RESULTS: Patients with Chagas' disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas' group 1 (54.7+/-6.6%; SD) and in group 2 (35.1+/-12.1%) were significantly lower than control group (66.7+/-2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas' disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001). CONCLUSIONS: Thus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease.     

Expression of major histocompatibility complex antigens and adhesion molecules in hearts of patients with chronic Chagas' disease

We have previously reported that heart lesions in patients with chronic cardiac Chagas' disease are composed predominantly of granzyme A+, cytolytic CD8+ T lymphocytes. We now pursue this study in the immunopathology of chronic chagasic cardiomyopathy by investigation of the expression of HLA antigens, and adhesion molecules in the hearts of seven chagasic patients with cardiac disease, two asymptomatic chagasic patients, and seven normal controls. Comparative immunohistochemical analyses show that HLA-ABC antigen expression is enhanced on the myocardial cells of chagasic patients with chronic cardiomyopathy, suggesting a possible role for these cells as targets for the CD8+ cytolytic lymphocytes dominant in these lesions. The HLA-DR antigens are not observed on myocardial cells, but are consistently upregulated on the endothelial cells in the hearts of patients with chronic chagasic cardiomyopathy. Intercellular adhesion molecule is expressed by endothelial cells of both chagasic and nonchagasic individuals, but E-selectin was detected only on vessels of hearts from chagasic patients who had chronic cardiomyopathy. Most of the lymphocytes in these lesions express lymphocyte function antigen-1 (LFA-1), CD44, and very late antigen-4, and a few display weak expression of LFA-3. We propose that the expression of these adhesion molecules and major histocompatibility complex antigens by endothelial cells, myocardial cells, and lymphoid cells in these lesions contribute to the pathogenesis of chronic chagasic cardiomyopathy.     

Contribution of MRI in the evaluation of ischemic heart diseases

The high spatial and temporal resolution of MRI provides accurate identification of left ventricular endocardial and epicardial contours. Cine-MRI allows reliable and reproducible measurements of end-systolic and end-diastolic volumes, ejection fraction and left ventricular mass. These measurements are not based on any geometrical hypothesis and so remain valid in presence of ventricular deformation as observed after myocardial infarctions. The value of cine-MRI has been demonstrated in ischaemic heart disease for the study of regional left ventricular function, by analysis of left ventricular segmental function and systolic thickening of the myocardial walls. Cine-MRI may also be performed during pharmacological stress. In coronary patients without ventricular dysfunction at rest, stress cine-MRI enables detection of segmental wall motion abnormalities or reduction of systolic thickening in potentially ischaemic territories. Cine-MRI may contribute to be study of myocardial viability. Regional myocardial perfusion may also be assessed using the rapid sequences of imaging and contrast agents opacifying the intravascular compartment. In coronary patient, underperfused regions may there by be detected. The most rapid imaging techniques enable visualisation of the proximal segments of the coronary arteries and the measurement of blood velocity in the coronary arteries and the calculation of coronary reserve. Simultaneous analysis under basal conditions and after pharmacological stress of global and segmental left ventricular function and of myocardial perfusion, associated with the possibility of imaging the proximal coronary arteries and of measuring the velocity of coronary flow, makes MRI a complete non-invasive method of evaluating patients with ischaemic heart disease.     

Intraesophageal balloon distension test in Chagas' disease patients with noncardiac chest pain

Patients with Chagas' disease often have chest pain as a prominent symptom. The objective of this study was to compare the results of intraesophageal balloon distension in chagasic and nonchagasic patients with chest pain not caused by coronary obstruction. We studied 40 patients with chest pain and angiographically normal coronary arteries, 25 with a positive serologic test for Chagas' disease (Chagas group, 16 women, mean age 53+/-10 years), and 15 with a negative serologic test (control group, 11 women, mean age 46+/-10 years). All patients had radiologic and endoscopic examinations of esophagus, stomach, and duodenum, esophageal manometry with the acid infusion test in the distal esophagus, and intraesophageal balloon distension. None of them had esophageal dilation or any signs of cardiovascular disease. A 25-mm-long latex balloon located 10 cm above the lower esophageal sphincter was inflated and deflated over a period of 10 sec at 1-ml increments of air until the subjects reported chest pain or to a maximum volume of 20 mi. The test caused chest pain in 14 subjects in the control group (93%) and in 12 in the Chagas' disease group (48%, P < 0.05). The mean volume of air that caused chest pain was 10+/-3 ml in the control group and 15+/-4 ml in the Chagas' disease group (mean+/-SD, P < 0.05). The maximum intraesophageal pressure during the examination was higher in Chagas' disease patients with chest pain during balloon distension (60 +/- 21 mm Hg) than in patients who did not have chest pain (37 +/-18 mm Hg, P < 0.05) and did not differ from the control group (48+/-16 mm Hg, P > 0.05). With the other examinations there was no difference between groups or between patients with or without chest pain during the balloon distension test. Although esophagitis was observed in 47% of patients in the control group and in 40% of the Chagas' disease group, the acid infusion test was positive in 27% of patients in the control group and in 4% of patients in the Chagas' disease group. We conclude that, as compared to a group of patients with similar chest pain, chagasic patients are less sensitive to esophageal distension. Thus, it is unlikely that their chest pain is related to esophageal mechanisms.     

TRP trapped in fly signaling web

BACKGROUND: Recent reports indicate that myocarditis can be associated with acute myocardial ischemia and even myocardial infarction in patients with normal arteriograms. We therefore tested the hypothesis that patients with biopsy-proven myocarditis have endothelial dysfunction despite angiographically smooth epicardial coronary arteries. METHODS AND RESULTS: Graded concentrations of the endothelium-dependent vasodilator acetylcholine (10(-6) to 10(-4) mol/L) and for comparison, the non-endothelium-dependent vasodilator nitroglycerin (0.3 mg intracoronary), were infused into the left coronary arteries of 18 patients (mean age 47+/-9 years, 8 women and 10 men) with biopsy-proven myocarditis but without angiographically demonstrable coronary artery disease. Vascular responses were analyzed by quantitative coronary angiography. Three patients had an intact vasodilator response to acetylcholine concentrations of up to 10(-4) mol/L in all segments of the left coronary artery, with a mean dilatation of +9.9%+/-2%. In contrast, paradoxical constriction by acetylcholine occurred in 9 patients, who showed a mean change in coronary artery diameter of - 11%+/-3%. Six patients had no significant change in any segments in response to acetylcholine (-2.5%+/-4%). There was a significant inverse correlation between the number of T-lymphocytes in the myocardium and the response of the epicardial coronary arteries to acetylcholine (Pearson correlation coefficient -0.49, P=.03). CONCLUSIONS: It can be assumed that the process of myocarditis is associated with impairment of endothelium-dependent vasodilation in response to acetylcholine in most patients. Vasoconstriction in the presence of acetylcholine in myocarditis is likely to reflect an abnormality of endothelial function. Endothelial dysfunction of coronary arteries may explain the occurrence of myocardial ischemia in patients with myocarditis.     

Sublabial, transseptal, transsphenoidal approach to the pituitary region guided by the ACUSTAR I system

Myocardial infarction occurring in young people with angiographically normal coronary arteries is well described but the pathophysiology of this condition remains unknown. Coronary artery spasm in association with thrombus formation and minimal atheromatous disease or spontaneous coronary artery dissection are possible causes. Two young men presented with severe chest pain after acute alcohol intoxication and each sustained an extensive anterior myocardial infarction. Investigations including intravascular ultrasound showed no evidence of atherosclerotic coronary artery disease. Coronary artery spasm associated with acute alcohol intoxication as well as prothrombotic state and endothelial damage related to cigarette smoking may be mechanisms leading to acute myocardial infarction in these cases. Acute myocardial infarction occurs in young persons with normal coronary arteries and the diagnosis should be considered in young patients presenting with severe chest pain, particularly those abusing cocaine or alcohol, so that reperfusion therapy can be initiated promptly.     

Role of nitric oxide in coronary arterial vasomotion and the influence of coronary atherosclerosis and its risks

Healthy coronary vascular endothelium releases nitric oxide to modulate resting and dynamic coronary arterial tone. We studied the impact of atherosclerosis and/or its risks on endothelial nitric oxide release in response to metabolic stimuli by evaluating coronary vasomotor responses to atrial pacing before and after the inhibition of nitric oxide production by intracoronary NG-monomethyl-L-arginine (L-NMMA) (20 micromol/min) infusion. The study includes 34 patients (15 with coronary disease, 11 with normal coronary arteries and > or =1 risk factor, and 8 with normal coronary arteries and no risks). Coronary blood flow was derived from Doppler flow velocity (0.018-inch Doppler wire) and coronary diameter. L-NMMA infusion reduced coronary blood flow by 18 +/- 16% and coronary diameter by 10 +/- 9%. Responses were identical in all subgroups. Coronary blood flow responses to pacing were similar in all subgroups and were unaffected by L-NMMA (11 +/- 11 vs 13 +/- 9 ml/min; p = 0.26). Epicardial coronary vasodilation to control pacing occurred in patients with normal coronary arteries with (4.0 +/- 5.2%, p = 0.01) or without (8.0 +/- 5.2%, p = 0.03) risks, but not in patients with coronary disease (2.8 +/- 5.9%). L-NMMA abolished pacing-induced epicardial vasodilation in patients without coronary artery disease, producing a 1.8 +/- 5.1% response, which was similar in all subgroups. We conclude that microvascular responses to rapid atrial pacing are not mediated by nitric oxide. Flow-mediated epicardial coronary arterial responses may be nitric oxide dependent.     

Retrograde coronary artery flow in aortic valve disease

Retrograde coronary artery flow was observed angiographically in 43 patients with aortic stenosis and/or regurgitation. In the 24 patients with pure or predominant aortic stenosis, retrograde flow was seen in all 24 during end-systole. In the eight patients with pure aortic regurgitation, retrograde flow was seen mainly during end-diastole (6/8). Among the 11 patients with stenosis and regurgitation, retrograde flow was both end-systolic and enddiastolic. Dominant left coronary arteries were seen in 13 patients; 13 showed retrograde flow in the dominant arteries. Dominant right coronary arteries were seen in 25 patients: all 25 showed retrograde flow equally in the right and left coronary. Five of the 43 patients could not be evaluated for dominance because of coronary artery occlusions. The severity of retrograde flow did not correlate with usual clinical, hemodynamic or tension-stress parameters: angina, electrocardiographic abnormality, end-diastolic pressure or volume, end-systolic pressure or volume, ejection fraction, severity of aortic regurgitation, peak or mean valve gradient, aortic valve area, myocardial tension and stress calculations, or DPTI:SPTI. In summary, retrograde coronary artery flow was seen in all 43 patients with severe aortic valve disease. The time in the cardiac cycle when retrograde flow occurred was related to the type of valve disease. Retrograde flow was seen mainly in the coronary arteries supplying the left ventricle and may result from increased regional myocardial stresses.     

Reduced epicardial coronary vasodilator capacity in patients with left ventricular hypertrophy

BACKGROUND: Enlargement of the epicardial coronary arteries occurs in left ventricular (LV) hypertrophy as an adaptation to the increased coronary blood flow. METHODS AND RESULTS: Vasodilator capacity of the epicardial coronary arteries was determined in 44 patients. The dose-response relation of intracoronary nitroglycerin was assessed in 14 patients (7 control subjects and 7 patients with aortic stenosis [study A]) using quantitative coronary angiography. In a second study (B), vasodilator capacity of the epicardial coronary arteries was determined in 15 control subjects and 15 patients with valvular heart disease. In study A, a curvilinear dose-response relation with maximal vasodilation after 90 micrograms intracoronary nitroglycerin was found in both control subjects and patients with aortic stenosis. Vasodilator capacity was reduced in those with aortic stenosis, although sensitivity to nitroglycerin was similar in both groups. In study B, coronary circumferential length at baseline was larger in those with LV hypertrophy (12.2 +/- 2.2 mm) than in control subjects (8.6 +/- 1.5 mm; P < .001); after 100 micrograms intracoronary nitroglycerin, it increased to 12.9 +/- 2.2 mm (6 +/- 5%) in those with LV hypertrophy and to 10.3 +/- 1.5 mm (21 +/- 8%; P < .001) in control subjects. An inverse relation between baseline circumferential length and its percent increase after nitroglycerin was found (r = -.71, P < .001). CONCLUSIONS: Vasodilator capacity of the epicardial coronary arteries is reduced in patients with LV hypertrophy, although sensitivity to nitroglycerin is normal. This may be due to a flow-mediated decrease in coronary vasomotor tone and/or the occurrence of vascular remodeling with an enlargement of the coronary arteries.     

Normal coronary flow reserve in patients with mitral valve prolapse, a positive exercise test and normal coronary arteries

We studied 12 patients (eight females and four males), ages 30-46 years, with echocardiographically documented mitral valve prolapse and clinical suspicion of coronary artery disease, based on a history of chest pain (five patients), angina-like pain (three patients), a positive exercise stress electrocardiogram (12 patients) and a focally positive thallium-201 stress perfusion scan (three patients), who were referred for cardiac catheterization and found to have normal coronary arteries. Ten patients without evidence of heart disease served as controls. In all mitral valve prolapse patients, coronary flow velocity reserve was determined successively in the left anterior descending, left circumflex and right coronary arteries as the ratio of the maximum (after intracoronary papaverine) to the resting mean coronary flow velocity. Coronary flow reserve values were fairly similar in the mitral valve prolapse and control patients; all 12 mitral valve prolapse patients had normal coronary flow reserve ( > or = 3.5) in all three coronary arteries with no significant differences among the arteries tested. Mean values +/- 1 standard deviation of the coronary flow reserve (mitral valve prolapse vs control patients) were 4.7 +/- 0.5 vs 4.6 +/- 0.6 for the left anterior descending, 4.6 +/- 0.4 vs 4.6 +/- 0.3 for the left circumflex and 4.5 +/- 0.4 vs 4.4 +/- 0.5 for the right coronary artery (all P = non-significant). The subsets of mitral valve prolapse patients with different clinical "ischaemic' manifestations were similar in terms of the calculated coronary flow reserve in all three major epicardial coronary arteries. In conclusion, this study demonstrated that an inadequate regional coronary flow reserve does not account for the clinical manifestations of myocardial ischaemia and positive exercise tests in patients with mitral valve prolapse and normal coronary arteries.     

Thyrotoxicosis and lactate-producing angina pectoris with normal coronary arteries

Three patients with thyrotoxicosis are described, in whom the presenting symptom was severe cardiac pain at rest or on effort and who were admitted to hospital with suspected or proven myocardial infarction. All patients were studied by selective coronary arteriography and left ventriculography after thyroid function tests which confirmed thyrotoxicosis. There was no demonstrable disease of the major coronary arteries in any of the patients, yet myocardial infarction and left ventricular aneurysm were shown to be present in 1, and there was definite electrocardiographic evidence of ischaemia in all 3. In addition, under stress the myocardium of all 3 patients produced lactate. It is recommended that thyrotoxicosis be seriously considered in the differential diagnosis of cardiac pain, particularly in younger women. The cause of the pain seems related to the cellular effects of thyrotoxicosis on the myocardium and current views of these effects are summarised. Of the 3 patients, 1 died suddenly 6 months after becoming euthyroid, indicating that the disease may not be as benign as expected. A guarded prognosis and continued medical follow-up are recommended when thyrotoxicosis presents with angina pectoris even when normal coronary arteries have been demonstrated.     

Myocardial perfusion damage after mediastinal irradiation for Hodgkin''s disease: a thallium-201 single photon emission tomography study

Conflicting data have been reported on the incidence of myocardial abnormalities after mediastinal irradiation for Hodgkin's disease. We studied myocardial perfusion in 31 clinically asymptomatic patients (13 male, 18 female, mean age 35 years) 7 years (range 3-11 years) after mantle field radiotherapy. Thallium-201 tomoscintigraphic data were obtained after exercise, 4 h later and at rest (8-15 days later). Images were analysed visually and quantitatively (sectorial quantification of 201Tl uptake on the bull's eye images of the short-axis slices) compared with those of 35 subjects with a low likelihood of coronary artery disease. Twenty-five tomographic data sets were available. Images were visually abnormal in 21 patients (84%) showing an heterogeneous 201Tl uptake. In 68%, the sectorial 201Tl uptake was lower than the mean 201Tl uptake value minus 2 standard deviations measured in subjects with a low likelihood of coronary artery disease. Significant redistribution (quantitatively assessed > or = 10%) was present in 10 patients (40%). In most of the patients, the location and the shape of the defect(s) could not be anatomically related to an epicardial coronary vessel disease. These results indicate that after mediastinal irradiation the 201Tl myocardial uptake is frequently abnormal. The observed patterns suggest a disease of the small coronary vessels and/or the existence of a myocardial fibrosis rather than epicardial coronary artery disease.     

Comparison of myocardial contrast echocardiography and low-dose dobutamine stress echocardiography in predicting recovery of left ventricular function after coronary revascularization in chronic ischemic heart disease

BACKGROUND: Dobutamine stress echocardiography (DSE) and myocardial contrast echocardiography (MCE) can predict recovery of left ventricular function after myocardial infarction. DSE also has been shown to predict left ventricular functional recovery after revascularization in chronic ischemic heart disease, whereas MCE has not been evaluated in such patients. This study was performed to compare DSE and MCE in the prediction of left ventricular functional recovery after revascularization in patients with chronic ischemic heart disease. METHODS AND RESULTS: MCE and DSE were performed in 35 patients with chronic coronary artery disease and significant wall motion abnormalities (mean ejection fraction, 0.36 +/- 0.09). Regional wall motion was scored by use of a 16-segment model wherein 1 = normal or hyperkinetic, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic. Each segment was evaluated for contractile reserve by DSE and perfusion by MCE. Revascularization (coronary artery bypass graft [n = 13] and percutaneous transluminal coronary angioplasty [n = 10]) was successful in 23 patients. Follow-up echocardiograms were done to assess wall motion 30 to 60 days later. In 238 segments with resting wall motion abnormalities, perfusion was more likely to present than contractile reserve (97% versus 91%, P < .02). Revascularization resulted in functional recovery in 77 of 95 hypokinetic segments (81%) but only 18 of 57 akinetic segments (32%, P < .0001). DSE and MCE were not significantly different in predicting functional recovery of hypokinetic segments. In akinetic segments, DSE and MCE had similar sensitivities (89% versus 94%, respectively) and negative predictive values (93% and 97%, respectively) in predicting functional recovery. However, DSE had a higher specificity (92% versus 67%, P < .02) and positive predictive value (85% versus 55%, P < .02) than MCE in predicting functional recovery. CONCLUSIONS: Both contractile reserve by DSE and perfusion by MCE are predictive of functional recovery in hypokinetic segments after coronary revascularization in patients with chronic coronary revascularization in patients with chronic coronary artery disease. In akinetic segments, myocardial perfusion by MCE may exist in segments that do not recover contractile function after revascularization. Thus, contractile reserve during low-dose dobutamine infusion is a better predictor of functional recovery after revascularization in akinetic segments than perfusion.     

Angina pectoris caused by coronary microvascular spasm

BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.     

Structural organization and chromosomal localization of the human ribosomal protein L9 gene

Monoclonal antibodies (MoAbs) raised against Trypanosoma cruzi microsomal fraction (Mc) and cross-reactive with mammalian tissues were used to evaluate the ability of cross-reactive T. cruzi antigens to induce an immune response in Chagas' disease. Thus, we studied the ability of sera from Chagas' disease patients (CDP) with different degrees of cardiac dysfunction to block the immune recognition of these MoAb to the target antigen determining for each serum an inhibition index (II). By means of this approach we inferred that blocking of monoclonal antibody binding to T. cruzi microsomes by subjects' serum represents antibodies with the same reactivity. After serological and medical examinations, individuals were separated into the following groups: Chagas' disease patients without manifest cardiac involvement (CDP-0), CDP with suspected or borderline cardiac disease (CDP-1), CDP with moderate myocardial dysfunction (CDP-2), CDP with overt cardiac dysfunction (CDP-3) and controls including healthy subjects (HS) and patients with idiopathic myocarditis (IMP). The reactivity between MoAb 5F2 and its target antigen was significantly (p < 0.05) inhibited by sera from CDP irrespective of the clinical stage [CDP: n = 46, 50 +/- 20, mean II +/- SD: control: n = 16, 18 +/- 8]. Moreover, 5F2 was able to distinguish (p < 0.05) sera from CDP with mild disease (CDP clinical grade 0/1: n = 26, 34 +/- 18) from that of CDP with severe disease (CDP clinical grade 2/3: n = 20, 67 +/- 7). Moreover, the inhibitory capacity of sera from asymptomatic CDP (CDP-0) correlated with patients age (r = 0.66, p < 0.05). CDP-0 below or equal 40 years of age had results (n = 15, 25 +/- 13) comparable (p > 0.05) to that of controls while mean inhibition of CDP-0 over 40 years of age (n = 5, 60 +/- 5) was indistinguishable (p > 0.05) from that of patients with severe disease. Competitive assay with MoAb 5A9B11 also showed significant differences (p < 0.05) between sera from CDP (n = 46, 46 +/- 24) and controls (n = 13, 5 +/- 5). On the contrary, the differences observed between CDP with different cardiac involvement was not significant (mild: n = 26, 31 +/- 22; severe: n = 20, 66 +/- 11). However a thorough study of data from asymptomatic sera revealed the existence of two levels of reactivity, with low and high capacity to inhibit the reaction of 5A9B11 against Mc. On the contrary, CDP sera showed a blocking activity for 1A10C11 comparable to that of controls (CDP: n = 25, 19 +/- 9; control: n = 12, 14 +/- 6). Some cross-reactive MoAbs recognized epitopes partially composed of carbohydrates. Interestingly, 5F2 and 5A9B11 epitopes did not appear to have carbohydrates moieties. In summary, immunoinhibition assays revealed differences in the immune response of chronic chagasic patients against parasite epitopes. These results have opened the possibility to identify a prognosis marker of the disease suggesting the clinical utility of monitoring levels of these anti-Mc antibodies in patients with chronic Chagas' disease.     

Time course of coronary endothelial healing after injury due to ischemia and reperfusion

BACKGROUND: Although it has been demonstrated in short-term preparations that ischemia with early reperfusion results in coronary vascular injury manifested by abnormal endothelium-dependent relaxation and increased permeability to plasma proteins, it has not been clear whether these abnormalities are permanent or reversible. METHODS AND RESULTS: In a canine model, regional coronary ischemia was accomplished by 1 hour of left anterior descending coronary artery ligation, and follow-up studies were performed after reperfusion for 1 hour, 48 hours, 2 weeks, or 9 weeks. Vasorelaxation was measured in vitro with preconstricted epicardial coronary artery rings subjected to increasing concentrations of the endothelium-dependent vasodilator ADP and the endothelium-independent vasodilator nitroprusside. At 1 and 48 hours of reperfusion, relaxation of rings from the ischemic reperfused artery to ADP was blunted, but relaxation to nitroprusside was normal. At 2 weeks there was a nonsignificant trend toward a blunted response to ADP in the ischemic/reperfused rings, and at 9 weeks a completely normal response to ADP was observed. Coronary microvascular permeability was assessed by measurement of protein leak index (PLI), by using a double-isotope technique with autologous radiolabeled transferrin and erythrocytes. At 1 and 48 hours of reperfusion there were substantial increases in PLI in the previously ischemic regions, indicative of increased extravascular transferrin. There was a small increase in PLI at 2 weeks but a completely normal measurement at 9 weeks. Electron microscopy of ischemic/reperfused vessels demonstrated endothelial cell swelling and other abnormalities in epicardial arteries and the microcirculation at 48 hours of reperfusion but normal endothelium at 2 weeks of reperfusion. CONCLUSIONS: After 1 hour of regional coronary ischemia, coronary endothelial injury occurs early in reperfusion with abnormalities in epicardial coronary artery endothelium-dependent relaxation, coronary microvascular permeability, and both epicardial coronary artery and microvascular histology. This pattern of injury persists for at least 48 hours, but there is partial functional and complete histological recovery within 2 weeks and complete functional recovery within 9 weeks.     

Evaluation of enzyme-linked immunosorbent assay for the diagnosis of Helicobacter pylori infection in children from different age groups with and without duodenal ulcer

BACKGROUND: Myocardial ischemia induced by 5-fluorouracil (5-FU) is a relatively rare, but potentially serious, occurrence. Some case reports have indicated that recurrent ischemia may be prevented if 5-FU is resumed after pretreatment with antianginal therapy. METHODS: A 54-year old woman was diagnosed with stage IIA squamous cell carcinoma of the anus. Treatment with concurrent radiation and chemotherapy (mitomycin-C and 5-FU) was initiated with curative intent. RESULTS: The patient had no evidence of underlying coronary artery disease based on history, physical examination or ECG. Approximately 48 h after initiation of 5-FU infusion the patient developed anginal pain associated with ECG changes compatible with ischemia. After resolution of ischemia and ruling out of myocardial infarction, coronary arteriography demonstrated normal coronary arteries. In an attempt to prevent myocardial ischemia, calcium channel blocker and nitrate therapy was started, but anginal pain with ECG change recurred when 5-FU was resumed. This necessitated selection of an alternative chemotherapy regimen. CONCLUSIONS: Even in the presence of normal coronary arteries, antianginal therapy may not preclude the occurrence of potentially serious 5-FU induced myocardial ischemia. For patients who experience 5-FU-induced myocardial ischemia, development of alternative chemotherapy regimens should be considered.     

Pathogenesis of acute coronary syndromes

Coronary artery diseases may categorized into asymptomatic disease, angina pectoris, myocardial infarction, chronic heart failure, and sudden coronary death. Unstable angina, acute myocardial infarction, and sudden cardiac death are known as the acute coronary syndromes. Coronary atheroma is unstable in the patients with acute coronary syndromes. Stable plaques will be unstable when dynamic alterations occur. The alterations are plaque rupture, plaque hemorrhage, coronary thrombosis and vasospasm. They act each other. We analysed the histopathology of coronary arteries who died of acute myocardial infarction in 85 cases. It showed that the risk factors of plaque rupture are clusters of form cells, eccentric plaque with soft lipid rich core, and thinning of fibrous cap in atheroma. Most of these cases ruptured at edge of the atheroma.     

Impairment of regional fatty acid uptake in relation to wall motion and thallium-201 uptake in ischaemic but viable myocardium: assessment with iodine-123-labelled beta-methyl-branched fatty acid

In coronary artery disease, discrepancy in the uptake of thallium-201 and of methyl-branched fatty acid at rest has been described. The purpose of this study was to evaluate iodine-123 labelled beta-methyl-branched fatty acid (BMIPP) myocardial uptake and wall motion at rest in segments with stress-induced ischaemia identified by stress 201Tl tomography in patients with chronic coronary artery disease. 123I-BMIPP myocardial tomography was performed at rest and was compared with the findings of exercise-reinjection 201Tl tomography in 45 patients with chronic coronary artery disease. Regional wall motion was evaluated by contrast left ventriculography in 36 patients. Among 237 segments with reversible 201Tl defects, equally decreased uptake on both reinjection 201Tl and BMIPP images was observed in 93 (39%), more severely decreased uptake of BMIPP in 118 (50%) and more severely decreased uptake of reinjection 201Tl in 26 (11%). On the other hand, among 90 segments with non-reversible 201Tl defects, each pattern was observed in 71 (79%), 6 (7%) and 13 (14%) segments, respectively. When comparing the ischaemic segments with and without more severely reduced uptake of BMIPP than of reinjection 201Tl, wall motion was impaired to a greater extent in the segments with more severely reduced uptake of BMIPP than of reinjection 201Tl [severe hypo- or dyskinesis was present in 64 (70%) of 91 segments and in 24 (22%) of 110 segments, respectively, P<0.005]. In patients with chronic coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection 201Tl in the segments with stress-induced ischaemia, while in most of the fixed perfusion defects BMIPP and reinjection 201Tl uptake decreased concordantly. In ischaemic myocardium, wall motion was impaired to a greater extent in those segments which showed more severely reduced uptake of BMIPP than of reinjection 201Tl. In ischaemic but viable myocardium, discordant BMIPP uptake less than reinjection 201Tl uptake may indicate metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities. In conclusion, the combination of resting BMIPP and stress-reinjection 201Tl imaging may provide information on metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities.     

Presence of genomes of phage PBV-1 in the mycelia of the fungus Penicillium brevi-compactum

Progressive systemic sclerosis may be associated with focal myocardial fibrosis. Electrocardiographic abnormalities including conduction block are common in progressive systemic sclerosis but whether they are due to direct destruction of the specialized conduction tissue of the heart is uncertain. The conduction systems of 35 patients with progressive systemic sclerosis were studied. Of these 35 patients, 17 (50 per cent) had myocardial fibrosis of the type seen in progressive systemic sclerosis. In 10 of the 17, it was severe. Sinus node fibrosis was present in 13 patients and was nearly as frequent in those with as in those without the progressive systemic sclerosis myocardial lesion. Overlying pericarditis may have contributed to the fibrotic changes within the sinoatrial nodes in seven of the 13 patients. The atrioventricular node and main His bundles were normal. However, fibrotic changes were found in the proximal bundle systems in six patients. In three of the six, severe myocardial progressive systemic sclerosis was present, two had focal fibrous atrophy of the left bundle, and one had complete interruption of the right bundle. In only the latter patient was this reflected in the electrocardiogram which showed a right bundle branch block. Three patients without progressive systemic sclerosis myocardial lesions also had fibrous atrophy of a portion of the proximal left bundle branch, and in one the electrocardiogram showed an isolated left anterior hemiblock. Thus, morphologic abnormalities within the conduction system in our patients are difficult to attribute to progressive systemic sclerosis per se. Furthermore, although conduction abnormalities were more frequent in patients with myocardial disease, specific conduction system disease was not the cause in most patients. As has been noted in ischemic heart disease, the conduction system appears to be relatively spared from the myocardial changes of progressive systemic sclerosis, and the high incidence of conduction disturbances in this condition may be a consequence, rather, of damage to working myocardium.