Diminished contractile reserve in patients with left ventricular hypertrophy and increased end-systolic stress during Dobutamine stress echocardiography

Left ventricular hypertrophy (LVH) is associated with decreased contractile response to inotropic stimulation in animal models, but this has not been documented in humans. To determine whether LVH is associated with decreased myocardial contractile reserve, we measured left ventricular mass, heart rate-corrected velocity of circumferential fiber shortening (Vcfc), end-systolic stress, and LV ejection fraction (LVEF) in patients with LVH and increased end-systolic stress (n = 6) and in patients without LVH (n = 7) who had a normal response to dobutamine stress echocardiography (increased LVEF and no wall motion abnormalities). The afterload-dependent indexes of left ventricular systolic performance were normal at baseline and showed significant increases at peak dobutamine dose (LVH group: Vcfc 0.91 +/- 0.11 to 1.76 +/- 0.59, p = 0.006; LVEF 49 +/- 5 to 65 +/- 6, p = 0.001; group without LVH: Vcfc 1.16 +/- 0.24 to 1.99 +/- 0.36, p = 0.001; LVEF 61 +/- 6 to 68 +/- 6, p = 0.05). The Vcfc/ end-systolic stress relation, a load-independent index of myocardial contractility, rose in a dose-dependent fashion in both groups, but the increment was significantly less for patients with LVH (p < 0.02), suggesting a blunted myocardial contractile reserve to inotropic stimulation. The change in heart rate-corrected velocity of circumferential fiber shortening per unit of change in end-systolic stress in each patient at each dobutamine dose showed a linear and inverse relationship. The increment in heart rate-corrected velocity of circumferential fiber shortening for a given reduction in end-systolic stress was larger in patients without LVH than in patients with LVH (p = 0.01). These results suggest that in patients with LVH and increased end-systolic stress, ventricular performance is maintained at the expense of limited myocardial contractile reserve, and that inotropic stimulation unmasks this abnormality, despite a normal response in LVEF and velocity of circumferential fiber shortening. This approach may identify patients with LVH at risk of developing systolic dysfunction and heart failure.     

Studies of the coronary circulation in Chagas' heart disease

Pathogenesis of chronic Chagas' heart disease may include various disturbances in the coronary circulation, that could be responsible for the myocardial lesions seen in human hearts and in experimental models of the disease. In this paper we critically reviewed the anatomical and functional abnormalities described in chronic chagasic patients, pertaining to the so-called vascular pathogenetic theory of Chagas' disease. The epicardial coronary arteries are usually free of significant obstructive disease in nonselected groups of chagasic patients examined at autopsy or by coronary angiography. However, chagasic patients who were studied after an episode of acute myocardial infarction, show the same patterns of atherosclerotic coronary artery disease seen in the general nonchagasic population. Studies of chagasic patients with angiographically normal coronary arteries, by several scintigraphy methods, revealed myocardial perfusion abnormalities which may be caused by the microcirculatory derangements described in animals experimentally infected with the T. cruzi. Since hypoperfusion has been detected in regions with normal or mildly impaired wall motion, it is likely that the microvascular disturbances precede and may be causative mechanism for the subsequent myocardial damage. We speculate that hibernating ventricular areas may occur in chagasic patients, on the basis of the evidence gathered from these studies. Recent investigations of chronic patients with Chagas' disease and chest pain showed attenuation of the vasomotor responses to physiological and pharmacological stimuli, in the epicardial coronary arteries.     

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.     

Chronic L-arginine treatment increases cardiac cyclic guanosine 5'-monophosphate in rats with aortic stenosis: effects on left ventricular mass and beta-adrenergic contractile reserve

OBJECTIVES: We tested the hypothesis that nitric oxide (NO) cyclic guanosine 5'-monophosphate (GMP) signaling is deficient in pressure overload hypertrophy due to ascending aortic stenosis, and that long-term L-arginine treatment will increase cardiac cyclic GMP production and modify left ventricular (LV) pressure overload hypertrophy and beta-adrenergic contractile response. BACKGROUND: Nitric oxide cyclic GMP signaling is postulated to depress vascular growth, but its effects on cardiac hypertrophic growth are controversial. METHODS: Forty control rats and 40 rats with aortic stenosis left ventricular hypertrophy ([LVH] group) were randomized to receive either L-arginine (0.40 g/kg/day) or no drug for 6 weeks. RESULTS: The dose of L-arginine did not alter systemic blood pressure. Animals with LVH had similar LV constitutive nitric oxide synthase (cNOS) mRNA and protein levels, and LV cyclic GMP levels as compared with age-matched controls. In rats with LVH L-arginine treatment led to a 35% increase in cNOS protein levels (p = 0.09 vs untreated animals with LVH) and a 1.7-fold increase in LV cyclic GMP levels (p < 0.05 vs untreated animals with LVH). However, L-arginine treatment did not suppress LVH in the animals with aortic stenosis. In contrast, in vivo LV systolic pressure was depressed in L-arginine treated versus untreated rats with LVH (163 +/- 16 vs 198 +/- 10 mm Hg, p < 0.05). In addition, the contractile response to isoproterenol was blunted in both isolated intact hearts and isolated myocytes from L-arginine treated rats with LVH compared with untreated rats with LVH. This effect was mediated by a blunted increase in peak systolic intracellular calcium in response to beta-adrenergic stimulation. CONCLUSIONS: Left ventricular hypertrophy due to chronic mechanical systolic pressure overload is not characterized by a deficiency of LV cNOS and cyclic GMP levels. In rats with aortic stenosis, L-arginine treatment increased cardiac levels of cyclic GMP, but it did not modify cardiac mass in rats with aortic stenosis. However, long-term stimulation of NO-cyclic GMP signaling depressed in vivo LV systolic function in LVH rats and markedly blunted the contractile response to beta-adrenergic stimulation.     

Diastolic function parameters and atrial arrhythmias in patients with arterial hypertension

OBJECTIVE: To investigate in patients with arterial hypertension (HT) the extent of left ventricular (LV) hypertrophy and diastolic function in relation to atrial arrhythmias. PATIENTS AND METHODS: In 112 hypertensive patients (40 women, 72 men; mean age 50 +/- 6.6 years) with a mean systolic blood pressure for the cohort of 170 +/- 5 mmHg, their first invasive coronary angiography was performed between July 1995 and October 1997 because of angina pectoris and/or an abnormal stress electrocardiogram. After excluding coronary heart disease LV dimensions and diastolic function were measured by echocardiography; in 59 of the 112 patients LV hypertrophy was demonstrated. In addition, long-term blood pressure monitoring, exercise and long-term electrocardiography, late-potential analysis and measurement of heart rate variability were undertaken. The control group consisted of 51 patients without arterial hypertension after exclusion of coronary heart disease. RESULTS: Even in the hypertensive patients without LV hypertrophy diastolic LV function and ergometric exercise capacity were reduced. The risk of LV arrhythmias was significantly higher in patients with LV hypertrophy than those without and in the control group, as measured by the complexity of atrial arrhythmias (P < 0.001), the incidence of abnormal late potentials (P < 0.001) and reduction in heart rate variability (29.3 +/- 5.3 ms vs 47.8 +/- 12.1 ms vs 60.7 +/- 6.6 ms; P < 0.001). There were similar results regarding severe complex atrial arrhythmias (38.5 vs 15.0 vs 0%; P < 0.001). The incidence of atrial arrhythmias correlated with the LV diameter (r = 0.68, P < 0.001), LV morphological dimensions and diastolic function (isovolumetric relaxation time r = 0.44, P < 0.001) and the ratio of early to late diastolic inflow (r = 0.46; P < 0.001). CONCLUSIONS: Hypertensive patients have a higher risk of atrial and ventricular arrhythmias, depending on the degree of LV hypertrophy. But atrial arrhythmias, in contrary to ventricular arrhythmias, are also closely related to abnormalities in LV diastolic function.     

Biphasic response to dobutamine predicts improvement of global left ventricular function after surgical revascularization in patients with stable coronary artery disease: implications of time course of recovery on diagnostic accuracy

OBJECTIVES: This study sought to evaluate the time course of improvement of left ventricular (LV) dysfunction in stable patients and its implications on the accuracy of dobutamine echocardiography for predicting improvement after surgical revascularization. BACKGROUND: Little is known about the optimal timing for evaluation of postrevascularization recovery of the contractile function of viable myocardium. METHODS: Sixty-one patients with chronic ischemic LV dysfunction scheduled for elective surgical revascularization were prospectively selected. They underwent dobutamine echocardiography (5 to 40 microg/kg body weight per min) and radionuclide ventriculography both preoperatively and at 3-month follow-up. At 14 months, another evaluation of LV function was obtained. To analyze echocardiograms, a 16-segment model and a five-point scoring system were used. Dyssynergic segments were considered likely to recover in the presence of a biphasic contractile response to dobutamine. Improvement of global function was defined as a > or =5% increase in LV ejection fraction (LVEF). RESULTS: Of the 61 patients, LVEF improved in 12 at 3 months and in 19 at late follow-up (from 32+/-8% to 42+/-9%, p < 0.0001). The frequency and time course of improvement of LVEF were similar in patients with mild and severe LV dysfunction. A biphasic response, identified in 186 of the 537 dyssynergic segments, was predictive of recovery in 63% at 3 months and in 75% at late follow-up. The positive predictive value was best in the most severe dyssynergic segments (90% vs. 67%). Other responses were highly predictive for nonrecovery (92%). The sensitivity and specificity for improvement of global function on a patient basis (> or =4 biphasic segments) were 89% and 81%, respectively, at late follow-up. CONCLUSIONS: Serial postoperative follow-up studies demonstrate incomplete recovery of contractile function at 3 months. The diagnostic accuracy of dobutamine echocardiography for predicting recovery is dependent on three factors: the combining of low and high dobutamine dosages, the severity of regional dyssynergy and the timing of evaluation.     

Effect of chronotropic and inotropic stimulation on the coronary pressure-flow relation in left ventricular hypertrophy

Left ventricular hypertrophy (LVH) secondary to chronic pressure overload is associated with increased susceptibility to myocardial hypoperfusion and ischemia during increased cardiac work. The present study was performed to study the effects of chronotropic and inotropic stimulation on the coronary pressure-flow relation of the hypertrophied left ventricle of dogs and to determine the individual contributions of increases in heart rate and contractility to the exaggerated exercise-induced increases in effective back pressure (pressure at zero flow; Pzf). Ascending aortic banding in seven dogs increased the LV to body weight ratio to 7.7 +/- 0.3 g/kg compared to 4.8 +/- 0.2 g/kg in 10 normal dogs (p < or = 0.01). Maximum coronary vasodilation was produced by intracoronary infusion of adenosine. During resting conditions maximum coronary blood flow in the pressure overloaded hypertrophied left ventricle was impaired by both an increase in Pzf (25.1 +/- 2.6 vs 13.8 +/- 1.2 mmHg in hypertrophied vs normal ventricles, respectively, p < or = 0.01) and a decrease in maximum coronary conductance (slope of the linear part of the pressure-flow relation, slopep > or = linear) (8.6 +/- 1.1 vs 12.7 +/- 0.9 ml/min/mmHg, p < or = 0.01). Right atrial pacing at 200 and 250 beats/min resulted in similar rightward shifts of the pressure-flow relation in hypertrophied and normal hearts with 3.1 +/- 0.8 and 4.7 +/- 0.8 mmHg increases in Pzf in LVH and normal dogs, respectively; stepwise multivariate regression analysis indicated that the exaggerated decrease in filling pressure (10 +/- 2 vs 6 +/-2 mmHg) and decrease in left ventricular systolic pressure (45 +/- 5 vs 3 +/- 3 mmHg, p < or = 0.01) may have blunted a greater rightward shift of the pressure-flow relation produced by atrial pacing in the hypertrophied hearts. Inotropic stimulation with dobutamine (10-20 micrograms/kg/min, i.v.) resulted in minimal flow changes in normal hearts but produced a 4.4 +/- 1.5 mmHg (p < or = 0.05) rightward shift of the pressure-flow relation in hypertrophied hearts. which correlated with a greater increase in left ventricular systolic pressure (83 +/- 16 vs 18 +/- 4 mmHg. p < or = 0.05). Exercise resulted in a rightward shift in both normal and hypertrophied left ventricles, but the increase in Pzf was significantly greater in the hypertrophied hearts (15.2 +/- 0.9 vs 10.3 +/- 0.9 mmHg. p < or = 0.05). Stepwise multivariate regression analysis indicated that not only increases in left ventricular filling pressure, but also increases in heart rate and LV systolic pressure contributed to the abnormally great increase in effective coronary back pressure which results in limitation of myocardial perfusion during exercise in the pressure overloaded hypertrophied left ventricle.     

A case report of ulcerative colitis complicated with protein losing enteropathy and colon cancer in a young female

AIMS: To assess the ability of dobutamine echocardiography to detect multivessel coronary artery disease and to determine predictive factors for multivessel disease with or without beta-blockers. PATIENTS AND METHODS: A total of 101 patients underwent dobutamine stress echocardiography and coronary angiography (evaluation of chest pain 76, extent of coronary disease after myocardial infarction 19, other indications 6). RESULTS: Ten patients in whom the test was prematurely terminated were excluded. Out of 91 patients who underwent dobutamine echocardiography, 54 patients had multivessel disease (sensitivity of dobutamine test 93%, specificity 46%). Heart rate at the maximum dose of dobutamine or atropine was 88 +/- 21 beats/min for multivessel diseases and 104 +/- 21 beats/min without multivessel disease (p < 0.001). A cut-off value < 94 beats/min discriminated patients at risk for multivessel disease. After adjusting for treatment with beta-blockers, heart rate < 94 beats/min, ECG signs of ischemia, and abnormalities on baseline echocardiogram with remote asynergies during dobutamine testing were independent predictors of multivessel disease in the multivariate analysis (probability > 90% when at least two factors were present). CONCLUSION: A heart rate < 94 beats/min at peak dose of dobutamine or after atropine, ECG signs of ischemia, and the presence of abnormalities on echocardiogram at rest with remote asynergies during dobutamine stress testing were independent predictive factors of multivessel coronary artery disease.     

Primary rhabdomyosarcoma of the brain: observations on a case with clinical and radiological evidence of cure

BACKGROUND: After heart transplantation, accelerated coronary vasculopathy is a major factor that limits long-term survival and is usually detected by serial coronary angiography. The aim of this study was to determine whether dobutamine stress echocardiography could accurately identify the progression of cardiac allograft vasculopathy. METHODS: Two sequential controls by dobutamine stress echocardiography were performed at an 18-month interval in 37 heart transplant recipients at the time of their routine coronary angiography. The first control (control 1) occurred 37+/-20 months after transplantation, and the second control (control 2) occurred after 56+/-21 months. Standard echocardiographic views were acquired at baseline and at incremental dobutamine infusion levels. Regional wall motion score was calculated in a 16-segment model, and each segment was graded from 1 (normal) to 4 (dyskinesia). Visual and quantitative coronary angiographic analysis were used to assess the severity of the coronary vasculopathy. RESULTS: The incidence of coronary vasculopathy increased from 46% (17/37 patients, four of whom had stenoses > 50%) at control 1 fo 70% (26/37 patients, six of whom had stenoses > 50%) at control 2. Progression of coronary vasculopathy was diagnosed by coronary angiography in 25 patients (new abnormalities in 19 and worsening of previous abnormalities in 6). Dobutamine stress echocardiography correctly identified the progression of vasculopathy in 21 of these 25 patients (84%) with new abnormalities in 17 and worsening in four. In the four remaining patients with evidence of progression of vasculopathy on coronary angiography, the result of dobutamine stress echocardiography was abnormal in three patients and normal in only one. Therefore dobutamine stress echocardiography results were abnormal in 12 patients at control 1 (sensitivity: 65%, specificity: 95%) and in 27 at control 2 (92% sensitivity, 73% specificity). CONCLUSION: Dobutamine stress echocardiography is a sensitive, noninvasive method to diagnose the progression of allograft vasculopathy, and a negative test result is a strong predictor of absence of allograft coronary vasculopathy. Therefore serial routine coronary angiography may be deferred when dobutamine stress echocardiography results are normal.     

Comparison of coronary endothelial dynamics with electrocardiographic and left ventricular contractile responses to stress in the absence of coronary artery disease

Coronary artery endothelial dysfunction has been proposed as a cause of myocardial ischemia and symptoms in patients with angina-like chest pain despite normal coronary angiograms, especially those with ischemic-appearing ST-segment depression during exercise (syndrome X). We measured coronary vasomotor responses to acetylcholine (3 to 300 microg/min) in 42 patients (27 women and 15 men) with effort chest pain and normal coronary angiograms who also had normal electrocardiograms and echocardiograms at rest. All patients underwent treadmill exercise testing and measurement of systolic wall thickening responses to dobutamine (40 microg/kg/min) during transesophageal echocardiography. There were no differences in the acetylcholine-stimulated epicardial coronary diameter (+5+/-13% vs +1+/-13%, p=0.386) and flow (+179+/-90% vs +169+/-96%, p=0.756), or in the systolic wall thickening responses (+134+/-65% vs +118+/-57%, p=0.445) from baseline values in the 12 syndrome X patients compared with the 30 patients with negative exercise test results. In patients in the lowest quartile of coronary flow responses to acetylcholine, dobutamine increased systolic wall thickening by 121+/-73%; 3 had ischemic-appearing ST-segment depression during this stress. This contractile response to dobutamine was no different than the increase in systolic wall thickening (129+/-48%, p=0.777) in patients in the highest quartile of coronary flow responses, 3 of whom also had ischemic-appearing ST-segment depression during this stress. Thus, coronary endothelial dysfunction in the absence of coronary artery disease does not account for ischemic-appearing ST-segment depression in patients with chest pain despite normal coronary angiograms. Further, coronary endothelial dysfunction is not associated with myocardial contractile responses to stress consistent with myocardial ischemia.     

Chronotropic response, safety, and accuracy of dobutamine stress echocardiography in patients with atrial fibrillation and known or suspected coronary artery disease

Ninety-two consecutive patients with atrial fibrillation (AF) who underwent dobutamine stress echocardiography were compared with a control group of patients in sinus rhythm matched for age, sex, and resting heart rate. Patients with AF had an increased chronotropic response to dobutamine, but there were no adverse effects and no evidence that the lower doses of dobutamine typically given to patients with AF were insufficient to induce ischemia.     

Cytotoxicity in patients with different clinical forms of Chagas' disease

There are few studies on cell-mediated cytotoxicity in human Chagas' disease. In the present study, we evaluated peripheral blood mononuclear cell (PBMC) cytotoxicity activity from chagasic patients with different clinical forms of disease. To verify the cytotoxic response, we performed cell lysis assays using 51Cr-labelled K562 cells as targets. Results are reported as lytic units (LU = number of cells required for 30% lysis) per million PBMC. Exposure of patients' PBMC to Trypanosoma cruzi antigen led to an increase in cytotoxic activity compared with unstimulated patient cells against K562. Asymptomatic cardiomyopathy patients had higher responses (37.8 +/- 5.0 LU/10(6) PBMC; mean +/- s.d.) than indeterminate (11.5 +/- 3.6 LU/10(6) and symptomatic cardiomyopathy (7.8 +/- 2.5 LU/10(6)). Normal control PBMC stimulated with T. cruzi antigen had 4.36 +/- 1.31 LU/10(6)) PBMC against K562. Addition of recombinant interferon-gamma (IFN-gamma) did not lead to significant increase in cytotoxicity in any group of patients. On the other hand, recombinant human IL-12 significantly increased cytotoxic responses from symptomatic cardiomyopathy patients and normal controls who presented low levels of cytotoxicity induced by T. cruzi antigen. The combined use of IL-12 and a neutralizing anti-IFN-gamma antibody did not change IL-12-induced cytotoxic responses, showing the direct role of this cytokine on natural killer (NK) cells. NK cells were the main cells responsible for the lysis of K562 target cells as evidenced by testing cell subsets following magnetic cell sorting. These data demonstrate that chagasic patients with different clinical forms of disease have PBMC which respond to T. cruzi antigen with a cytotoxic response, and this response is up-regulated by IL-12.     

Effects of critical coronary stenosis on global systolic left ventricular function quantified by pressure-volume relations during dobutamine stress in the canine heart

OBJECTIVES: In this study we quantified the effects of a critical coronary stenosis on global systolic function using pressure-volume relations at baseline and during incremental dobutamine stress. BACKGROUND: The effects of coronary stenosis have previously been analyzed mainly in terms of regional (dys)function. Global hemodynamics are generally considered normal until coronary flow is substantially reduced. However, pressure-volume analysis might reveal mechanisms not fully exposed by potentially load-dependent single-beat parameters. Moreover, no systematic analysis by pressure-volume relations of the effects of dobutamine over a wide dose range has previously been presented. METHODS: In 14 dogs left ventricular volume and pressure were measured by conductance and micromanometer catheters, and left circumflex coronary flow by Doppler probes. Measurements in control and with left circumflex stenosis were performed at baseline and at five levels of dobutamine (2.5 to 20 microg/kg/min). The end-systolic pressure-volume relation (ESPVR) dP/dtMAX vs. end-diastolic volume (dP/dtMAX - V(ED)) and the relation between stroke work and end-diastolic volume (preload recruitable stroke work [PRSW]) were derived from data obtained during gradual caval occlusion. RESULTS: In control, dobutamine gradually increased heart rate up to 20 microg/kg/min, the inotropic effect blunted at 15 microg/kg/min. With stenosis, the chronotropic effect was similar, however, contractile state was optimal at approximately 10 microg/kg/min and tended to go down at higher levels. At baseline, the positions of ESPVR and PRSW, but not of dP/dtMAX - V(ED), showed a significant decrease in function with stenosis. No differences between control and stenosis were present at 2.5 microg/kg/min; the differences were largest at 15 microg/kg/min. CONCLUSIONS: Pressure-volume relations and incremental dobutamine may be used to quantify the effects of critical coronary stenosis. The positions of these relations are more consistent and more useful indices than the slopes. The positions of the ESPVR and PRSW show a reduced systolic function at baseline, normalization at 2.5 microg/kg/min and a consistent significant difference between control and stenosis at dobutamine levels of 5 microg/kg/min and higher.     

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.     

Myocardial contrast echocardiography versus dobutamine echocardiography for predicting functional recovery after acute myocardial infarction treated with primary coronary angioplasty

OBJECTIVES: We sought to compare myocardial contrast echocardiography with low dose dobutamine echocardiography for predicting 1-month recovery of ventricular function in acute myocardial infarction treated with primary coronary angioplasty. BACKGROUND: The relation between myocardial perfusion and contractile reserve in patients with acute myocardial infarction, in whom anterograde flow is fully restored without significant residual stenosis, is still unclear. METHODS: Thirty patients with acute myocardial infarction treated successfully with primary coronary angioplasty underwent intracoronary contrast echocardiography before and after angioplasty and dobutamine echocardiography 3 days after the index infarction. One month later, two-dimensional echocardiography and coronary angiography were repeated in all patients and contrast echocardiography in 18 patients. RESULTS: After coronary recanalization, 26 patients showed myocardial reperfusion within the risk area, although 4 did not. At 1-month follow-up, all patients had a patient infarct-related artery without significant restenosis. Both left ventricular ejection fraction and wall motion score index within the risk area significantly improved in the patients with reperfusion ([mean +/- SD] 38 +/- 8% vs. 48 +/- 12%, p < 0.005; and 2.35 +/- 0.5 vs. 2 +/- 0.6, p < 0.001, respectively), but not in those with no reflow. Of the 72 nonperfused segments before angioplasty, 27 showed functional improvement at follow-up. Myocardial contrast echocardiography had a sensitivity and a negative predictive value similar to dobutamine echocardiography in predicting late functional recovery (96% vs. 89% and 89% vs. 93%, respectively), but a lower specificity (18% vs. 91%, p < 0.001), positive predictive value (41% vs. 86%, p < 0.001) and overall accuracy (47% vs. 90%, p < 0.001). CONCLUSIONS: Microvascular integrity is a prerequisite for myocardial viability after acute myocardial infarction. However, contrast enhancement shortly after recanalization does not necessarily imply a late functional improvement. Thus, contractile reserve elicited by low dose dobutamine is a more accurate predictor of regional functional recovery after reperfused acute myocardial infarction than microvascular integrity.     

Effect of MCI-154, a cardiotonic agent, on regional contractile function and myocardial oxygen consumption in the presence and absence of coronary artery stenosis in dogs

The effects of MCI-154 (6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)- pyridazinone hydrochloride.3H2O), a cardiotonic agent with calcium sensitizing actions, on regional contractile function and myocardial oxygen consumption (MVO2) were studied in the dog hearts with and without partial occlusion of the left anterior descending coronary artery and compared with those of dobutamine. Segment shortening by sonomicrometry, regional myocardial blood flow by microspheres and the oxygen content of coronary venous blood drawn from the ischemic left anterior descending coronary artery area were simultaneously measured. The ischemic zone segment shortening and left ventricular (LV) dP/dtmax were decreased after partial occlusion. The infusion of MCI-154 starting 20 min after ischemia improved the depressed segment shortening and LV dP/dtmax without increasing the ischemic zone MVO2 and regional myocardial blood flow. In the nonischemic hearts, MCI-154 did not increase MVO2 and coronary blood flow despite the augmentation of myocardial contractility. MCI-154 decreased LV end-diastolic pressure and systemic blood pressure. On the other hand, dobutamine failed to increase the ischemic zone segment shortening, but the drug increased MVO2, coronary blood flow and LV dP/dtmax in both ischemic and nonischemic hearts. These results indicate that MCI-154 alleviates the ischemic contractile failure without increasing myocardial oxygen demand. Thus, MCI-154 may be useful in the management of heart failure with reduced coronary reserve.     

Responses of blood flow, oxygen consumption, and contractile function to inotropic stimulation in stunned canine myocardium

To examine the effects of inotropic stimulation on regional myocardial blood flow (MBF), oxidative metabolism, and contractile function in stunned myocardium, nine closed-chest dogs were studied 2 hours postreperfusion after a 25 minute occlusion of the left anterior descending coronary artery (LAD). MBF was determined with microspheres, and regional myocardial oxygen consumption (MVO2) was estimated from the rate constant k1 of the rapid clearance phase of [1-11C] acetate time activity curves, recorded with dynamic positron emission tomography. Myocardium at risk was determined from [13N] ammonia images obtained during occlusion. Wall motion, assessed by two-dimensional echocardiography, was impaired in postischemic myocardium in all dogs 2 hours after reperfusion. Dobutamine infusion increased the rate pressure product by 70% +/- 31% and significantly improved contractile function in the postischemic region in all dogs. In remote myocardium, MVO2 increased from 5.7 +/- 1.2 to 8.6 +/- 1.6 mumol/gm/min, and blood flow from 0.87 +/- 0.16 to 1.52 +/- 0.42 ml/gm/min in response to dobutamine. In reperfused myocardium, MVO2 increased from 3.1 +/- 0.7 to 7.4 +/- 1.5 mumol/gm/min, and blood flow from 0.51 +/- 0.12 to 1.2 +/- 0.4 ml/gm/min. Oxygen extraction increased significantly in reperfused myocardium relative to remote myocardium consistent with a flow-limited response to dobutamine stimulation. The improvement in contractile function failed to correlate significantly with relative increases in MBF or MVO2, suggesting that mechanical function is not as tightly coupled as MBF and MVO2 in postischemic myocardium during inotropic stimulation.     

Abnormal progression of a liquid meal through the stomach and small intestine in patients with Chagas' disease

This study describes the abnormal pattern of gastrointestinal progression of a liquid meal in patients with the digestive form of chronic Chagas' disease. This condition is known as a natural model of intramural denervation of the gut. Sixteen patients with clinical and radiographic evidence of esophageal and/or colonic involvement and 18 healthy volunteers were studied. Orocecal transit time after the ingestion of a 10% lactulose solution (180 ml) tagged with 99mtechnetium was measured by a conventional H2 breath technique. Gastric emptying and the arrival of the front of the meal to regions of interest corresponding to proximal and distal areas of the small intestine were assessed by abdominal scintigraphy. Orocecal transit time was significantly greater (P < 0.05) in Chagas' disease patients (N = 13) than in control subjects (N = 18) (mean +/- SD: 100.7 +/- 48.7 min vs 62.9 +/- 18.2 min). Half-time for gastric emptying of liquids in chagasic patients (N = 9) was significantly lower (P < 0.01) than in controls (N = 7) (9.7 +/- 2.7 min vs 26.4 +/- 3.4 min). The time of arrival of the liquid meal to the proximal small intestine was also significantly shorter (P < 0.02) in patients than in controls (5.6 +/- 3.7 vs 11.4 +/- 5.5 min), but there was no difference between the two groups concerning the time the meal first arrived to the distal small intestine (15.0 +/- 11.0 min vs 23.5 +/- 11.4 min, P > 0.05). These results indicate that patients with Chagas' disease have a combination of exceedingly rapid gastric emptying and abnormally delayed transit of liquids through the more distal segments of the small bowel.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Can case-finding instruments be used to improve physician detection of depression in primary care?

The aim of this study was to examine the value of an additional atropine injection in patients who do not achieve an adequate heart rate during dobutamine infusion for myocardial perfusion SPET (single photon emission tomography). Patients undergoing dobutamine myocardial SPET who failed to achieve > or = 85% of their age-predicted maximal heart rate at the end of dobutamine infusion (D protocol) had a second dobutamine myocardial SPET study on a separate day with the addition of an atropine injection during the dobutamine infusion (D + A protocol). Twenty-nine patients were studied. 201Tl was used in 27 patients and 99Tc(m)-MIBI in two patients. All patients underwent coronary angiography and significant coronary artery disease was found in 19 of 29 patients. The mean heart rate obtained at the peak of dobutamine infusion in the D + A protocol was significantly higher than that in the D protocol (153.8 +/- 13.8 vs 117.5 +/- 15.3 beats min[-1]). The D + A protocol resulted in a higher diagnostic sensitivity for the detection of stenosed coronaries compared with the D protocol (87 vs 80%, P > 0.05) without changing the specificity (89% for both protocols). On the other hand, the frequency of side-effects and ECG changes during the D + A protocol was higher than that with the D protocol (32 vs 47). In conclusion, the addition of an atropine injection during dobutamine infusion resulted in a higher diagnostic sensitivity for identifying stenosed coronaries compared to dobutamine alone.