Effects of beta-blockade and atropine on ischemic responses in left ventricular regions subtending coronary stenosis during dobutamine stress echocardiography

OBJECTIVES: This study was designed to examine the effects of a beta-adrenergic blocking agent on the ischemic response to dobutamine stress and to determine the degree to which these effects can be abolished by the addition of atropine. BACKGROUND: Whether beta-blockade affects the sensitivity of dobutamine stress echocardiography for the diagnosis of coronary artery disease has been controversial. METHODS: In nine pigs, a left anterior descending coronary artery stenosis was created to reduce flow reserve (maximal/rest flow) to 1.1 to 1.9 without baseline regional wall motion abnormalities. This corresponded to a 50% to 90% diameter stenosis. Wall thickening was measured using epicardial echocardiography. Regional lactate production and coronary venous pH were monitored from an adjacent cardiac vein. A standard protocol of dobutamine stress echocardiography was first performed. After normalization of the ischemic abnormalities elicited with this infusion, esmolol was infused at 50 micrograms/kg body weight per min and the dobutamine test was repeated, with 1.0 mg of atropine added at the maximal dobutamine dose. RESULTS: Without esmolol, dobutamine stress induced myocardial ischemia with a reduction in regional wall thickening and lactate production in all nine pigs. Multiple regression analysis revealed that coronary flow per heartbeat (p < 0.01) and lactate production (p < 0.05) independently correlated with regional wall thickening during dobutamine stress. The beta-blocker significantly reduced heart rate and regional oxygen consumption and altered the relation between coronary flow per heartbeat and regional wall thickening (p < 0.05) during dobutamine stress. Esmolol prevented dobutamine-induced ischemia (lactate production and wall motion abnormalities) in seven of nine pigs. The addition of atropine induced lactate production and a reduction in wall thickening in five of seven pigs in which ischemia had been prevented by beta-blockade. However, lactate production was higher and regional venous pH was lower with the baseline dobutamine infusion than with that performed after esmolol with atropine added at the maximal dobutamine dose (p < 0.05). CONCLUSIONS: A correlation between regional wall thickening and coronary flow per heartbeat was demonstrated during baseline dobutamine stress. Beta-blockade shifted this relation so that dobutamine stress-induced myocardial ischemia was attenuated. The mechanisms by which beta-blockade prevents dobutamine-induced ischemia appeared to be mainly through decreases in heart rate and rate of rise in left ventricular pressure, improvement of regional coronary flow per heartbeat and attenuation of regional ischemic lactate production. Adding atropine in conventional doses enhanced the ability of dobutamine stress to induce myocardial ischemia but did not completely abolish the effects of beta-blockade on either the severity of dobutamine-induced wall thickening abnormalities or regional metabolic disturbances.     

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.     

Regional cardiac sympathetic nerve dysfunction and the diagnostic efficacy of metaiodobenzylguanidine tomography in stable coronary artery disease

The present study endeavors to correlate regional myocardial sympathetic nerve dysfunction with reversible and persistent perfusion abnormalities and depressed regional wall motion, and to determine the diagnostic efficacy of radio-iodinated metaiodobenzylguanidine (MIBG) tomography for detecting coronary artery disease. In 28 consecutive patients with stable coronary artery disease and 7 patients with atypical chest pain but no coronary stenosis, regional MIBG uptake was semiquantitatively evaluated in 13 left ventricular segments early (30 minutes) and late (4 hours) after injection. Regional MIBG uptake was reduced in 68 of 90 segments (76%) showing reversible perfusion abnormality and 72 of 81 segments (89%) showing persistent abnormality 4 hours after injection. Although the sensitivity and negative predictive values of late MIBG scanning for detecting myocardial perfusion abnormalities were relatively high (82% and 85%, respectively), the specificity, positive predictive value, and kappa value were low (63%, 57%, and 0.41, respectively). Right coronary lesions were detected by late MIBG scanning with a high sensitivity (85%) but a low specificity (41%). Conversely, the sensitivities for detecting lesions in the other 2 major left coronary arteries were low (55%). The overall diagnostic accuracy of late MIBG scanning was 66% and the positive and negative predictive values and kappa value were low; 60%, 70%, and 0.31, respectively. Similarly, regional sympathetic dysfunction was observed in 42 of 49 asynergic segments (86%) on late MIBG scans, of which 32 segments were viable and 10 nonviable; but the low specificity (73%) and positive predictive value (44%) reduced the kappa value (0.43). Thus, regional cardiac sympathetic innervation is impaired in ischemic, asynergic but noninfarcted myocardium as well as in myocardium which is infarcted or has a persistent perfusion abnormality. The diagnostic efficacy of MIBG tomography to detect coronary artery disease, however, is limited probably because of nonspecific reductions of MIBG uptake in the inferior and posterolateral regions.     

Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high Bax:Bcl-2 ratio

BACKGROUND: When patients with severely depressed left ventricular function are treated, it is crucial to know in advance how much functional recovery is expected from coronary revascularization. METHODS AND RESULTS: We compared the results of 11C acetate positron emission tomography (PET) with dobutamine infusion with changes in regional wall motion evaluated by left ventriculography in 28 patients with old Q-wave anterior myocardial infarctions. Dysfunctional but viable myocardium (group A, n = 13) was separated from nonviable myocardium (group B, n = 15) by echocardiographic assessments of regional wall motion before and after successful coronary revascularization. 11C acetate PET was performed to characterize normalized myocardial blood flow and oxidative metabolism (the clearance rate constant, k mono). While the baseline k monos of the infarct areas of the two groups were different with overlap, the responses to dobutamine infusion were directionally different. In addition, relative perfusion by 11C acetate PET could predict recovery of left ventricular function as well as or better than dobutamine 11C acetate kinetics. The extent of the increase in k monos of the infarct area with dobutamine infusion correlated well (P < .01) with the degree of the increase in the percentage of systolic segment shortening in the infarct area (left ventriculography) after coronary revascularization. CONCLUSIONS: 11C acetate PET with dobutamine infusion can predict not only the reversibility of dysfunctioning myocardium after coronary revascularization but also the extent of improvement of regional wall motion in patients with old Q-wave infarction.     

Value of dobutamine echocardiography in the detection of coronary disease in heart transplant patient. Groupe de Recherche VACOMED]

The value of Dobutamine stress echocardiography in the detection of coronary artery disease in heart transplant patients was studied in 64 patients at control coronary angiography 39 +/- 14 months after transplantation. Dobutamine was infused at progressively increasing doses (5 to 40 micrograms/kg/min) at 5 minute intervals, in order to reach 85% of the theoretical maximal heart rate or an ischaemic event. Echocardiography was analysed in the 4 standard views which were digitised allowing calculation of a regional wall motion score under basal conditions and at peak dosage in 16 left ventricular segments. Coronary angiography identified three groups: group I: 29 patients with normal coronary arteries; group II: 17 patients with non-significant coronary disease (diffuse or localised stenosis < 50%); group III: 9 patients with significant (> 50%) coronary disease. Dobutamine stress echocardiography showed regional wall motion abnormalities in 2/29 patients in group I, 13/17 patients in group II and all patients in group III (global sensitivity: 85%; specificity: 97%). The contractility score was significantly higher under basal conditions in group III (1.45 +/- 0.54) than in group I (1) and group II (1.17 +/- 0.23). At peak dose, the contractility score was unchanged in group I and increased significantly (p < 0.01) in the other two groups. The authors conclude that Dobutamine echocardiography is a reliable, non-invasive method of detecting coronary disease in cardiac transplant patients, and is particularly valuable for demonstrating myocardial ischaemia related to coronary lesions judged to be not significant at coronary angiography.     

G1 accumulation caused by iron deprivation with deferoxamine does not accompany change of pRB status in ML-1 cells

In hypertension, several factors disturb coronary circulation and the metabolic reserve of the heart. This study was undertaken to test whether in hypertensive patients global and regional left ventricular (LV) function is related during exercise to the presence of significant coronary stenosis and whether lowering of coronary perfusion pressure through rapid normalization of the diastolic pressure may modify the dynamics of the left ventricle. Thirty-five patients with mild to moderate hypertension undergoing coronary angiography for the evaluation of chest pain were included in the study; upright bicycle exercise echocardiography tests were performed without therapy and 1 day later 1 h after sublingual administration of nifedipine. LV ejection fraction and regional wall motion scores were evaluated and compared at baseline, peak exercise, immediate postexercise, and recovery phases in each test through digital on-line storing of echocardiographic images. Twenty-one patients had normal coronary arteries (group 1) and 14 significant coronary stenoses (group 2); age, gender, heart rate, blood pressure, left ventricular diameter and mass index, and ejection fraction were similar in the two groups. At peak exercise LV ejection fraction slightly increased in group 1, whereas it slightly decreased in group 2 (both during the test without therapy and after nifedipine administration). All patients in group 1 had normal left ventricular wall motion during exercise; 13 of 14 patients in group 2 had LV wall motion abnormalities at peak exercise. Nifedipine did not produce any effect on LV regional wall motion in group 1, but it induced significant changes in LV regional wall motion in seven patients in group 2. Changes in LV wall motion between the two test groups were related to the number of the stenotic coronary vessels: the normal exercise test before and after therapy and the two normalized tests after nifedipine administration were in fact observed in patients with one-vessel disease, whereas worsening or changes in the site of ischemia were observed only in patients with multivessel disease. Regional and global left ventricular dynamics during exercise is mainly dependent on the existence of significant coronary artery disease. Rapid decrease of blood pressure does not alter the regional dynamics of the left ventricle during exercise in patients without coronary artery disease, but it may induce normalization, worsening, or changes in the site of wall motion abnormalities in hypertensives with significant coronary stenoses.     

Regional myocardial function

Methods for noninvasive tissue tracking and quantification of myocardial shortening with magnetic resonance imaging have been developed using presaturation tagging and velocity encoded phase maps. The concurrent development of rapid scanning techniques, such that a complete cine loop of a slice can be obtained in a breath-hold, has made the measurement of myocardial wall motion in patients a simple and reproducible examination. These methods make it possible to quantify the severity and extent of regional heart wall motion abnormalities both at rest and during stress.     

Technetium-99m sestamibi tomographic evaluation of residual ischemia after anterior myocardial infarction

OBJECTIVES: This study investigated the value of sestamibi scintigraphy in assessing residual ischemia after anterior myocardial infarction. BACKGROUND: Serial imaging with sestamibi, the uptake and retention of which correlate with regional myocardial blood flow and viability, has been used to estimate salvaged myocardium and risk area after acute infarction. We recently documented that recovery of perfusion and contraction in the infarcted area may continue well after the subacute phase, suggesting myocardial hibernation. Some underestimation of viability in the setting of hibernating myocardium by sestamibi imaging has been reported. METHODS: We studied 58 patients in stable condition after Q wave anterior infarction. Regional perfusion and function were quantitatively assessed by sestamibi tomography and two-dimensional echocardiography at 4 to 6 weeks and at 7 months after infarction. In sestamibi polar maps, abnormal areas with tracer uptake > 2.5 SD below our reference values were computed at rest and after symptom-limited exercise. On two-dimensional echocardiography the ejection fraction and extent of rest wall motion abnormalities were assessed by a computerized system. All patients had coronary angiography between the two studies. RESULTS: At 7 months the extent of rest sestamibi defect was significantly reduced in 40 patients (69%, group 1) and unchanged in 18 (31%, group 2). Rest wall motion abnormalities and ventricular ejection fraction significantly improved in group 1 but not in group 2. Underlying coronary disease, patency of the infarct-related vessel and rest sestamibi defect extent at 5 weeks were comparable between the two groups. At 7 months, an increase in the reversible (stress-rest defect) tracer defect was observed in group 1 (p < 0.05) despite a smaller stress-induced hypoperfusion (p < 0.05). Reversible sestamibi defects and stress hypoperfusion were unchanged in group 2. In 38 (95%) of 40 group 1 patients, the area showing reversible sestamibi defects at 7 months matched the area showing fixed hypoperfusion at 5 weeks. CONCLUSIONS: The reduction in the rest tracer uptake defect that can occur late after infarction may affect the assessment of ischemic burden by sestamibi imaging early after anterior myocardial infarction.     

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses

BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. METHODS AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term hibernation for 24 hours (n = 7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min-1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P < .05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.     

Predicting hemodialysis access failure with color flow Doppler ultrasound

Large surface-area burns in patients have been associated with a severe impairment in cardiac performance, as evidenced by a decline in cardiac output. The mechanisms responsible for this profound myocardial dysfunction are largely unknown. We investigated the effects of lymph isolated from the scalded hind limb of dogs on regional myocardial blood flow, coronary vascular reactivity, and contractile performance. Dogs were instrumented with ultrasonic dimension crystals in the myocardium supplied by the left anterior descending (LAD) and by the left circumflex (LCx) coronary arteries. After cannulating a hind limb lymphatic, lymph was infused directly into the LAD before and after a 10-second 100 degrees C hind limb scald. Scalding alone did not alter myocardial contractile performance in the LAD or LCx regions, coronary artery blood flow, or systemic hemodynamics. Interestingly, postburn lymph infused into the LAD resulted in a 38% decline in LAD zone segment shortening (p < 0.01 vs baseline) that lasted throughout the 5-hour observation period. In contrast, segment shortening in the (control) LCx region was unaffected by postburn lymph injections into the LAD. Regional myocardial blood flow (radiolabeled microspheres) in the LAD and LCx regions was unchanged after scald injury or intracoronary injection of postburn lymph. In addition, LAD coronary artery vascular reactivity to acetylcholine and nitroglycerin was also unaffected by the regional thermal injury or by injection of lymph into the LAD. These data suggest that a regional scald injury results in the production and release of a potent myocardial depressant factor(s) that produces a direct negative inotropic effect on the canine myocardium.     

Perioperative cardiac evaluation for noncardiac surgery noninvasive cardiac testing

Prognostic risk stratification to identify perioperative and long-term cardiac risk in selected patients undergoing noncardiac surgery is part of good clinical practice. Exercise variables associated with significant increased risk include poor functional capacity (eg, <4 metabolic equivalents), marked exercise-induced ST segment shift or angina at low workloads, and inability to increase or actually decrease systolic blood pressure with progressive exercise. Approximately 40% of patients tested before peripheral vascular surgery will have an abnormal exercise electrocardiogram (ECG). The predictive value for a perioperative event, ie, death or myocardial infarction, ranges from 5% to 25% for a positive test and 90% to 95% for a negative test. Whereas exercise cardiac imaging is the modality of choice in patients with a noninterpretable exercise ECG, pharmacological stress imaging should be used in the 30% to 50% of patients who require perioperative noninvasive risk stratification and are unable to perform an adequate level of exercise to test cardiac reserve. Myocardial perfusion variables predictive of increased cardiac events include severity of the perfusion defect, number of reversible defects, extent of fixed and reversible defects, increased lung uptake of thallium-201, and marked ST segment changes associated with angina during the test. The reported sensitivity and specificity of dobutamine-induced echocardiographic wall motion abnormalities in patients with peripheral vascular disease is similar to myocardial perfusion scintigraphy, but the confidence limits are wider due to the smaller sample size in these more recent studies. In conclusion, noninvasive cardiac testing should be used selectively in patients undergoing noncardiac surgery; the results provide useful estimates of short- and long-term risk of cardiac events, and the magnitude of abnormal response on noninvasive testing should be used to formulate decisions regarding the need for coronary angiography and subsequent revascularization.     

Mechanism of impaired left ventricular wall motion in the diabetic heart without coronary artery disease

OBJECTIVE: To elucidate whether impairment of the myocardial free fatty acid (FFA) metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease. RESEARCH DESIGN AND METHODS: We performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum. RESULTS: Nine patients with reduced wall motion documented by left ventriculography (LVG), (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 +/- 0.2, mean +/- SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 +/- 0.2, P < 0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P < 0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients. CONCLUSIONS: Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes.     

Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection

OBJECTIVES: We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND: FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS: Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS: There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS: FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.     

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.     

Interleukin-8 expression in bronchoalveolar lavage cells in the evaluation of alveolitis in idiopathic pulmonary fibrosis

OBJECTIVES: We evaluated the relationship between alterations in coronary flow velocity during the acute phase of acute myocardial infarction (AMI) and the recovery of left ventricular wall motion in patients who underwent successful primary angioplasty. BACKGROUND: The status of the coronary microcirculation is the major determinant of the prognosis of patients who have had successful reperfusion after AMI. Animal studies have shown that dynamic changes in regional flow are associated with the extent of infarction. Evaluation of alterations in coronary flow velocity in infarcted arteries may provide information about microcirculatory damage. METHODS: Flow velocity of the distal anterior descending artery was continuously monitored with the use of a Doppler guide wire immediately after recanalization for 18 +/- 4 h in 19 patients who underwent successful primary angioplasty after anterior AMI. Subjects were divided into two groups on the basis of the time course of alterations in average peak velocity (APV). Group D consisted of patients who had progressive decreases in APV through the next day (n = 9), and Group I comprised patients with an increase in APV after a transient decline (n = 10). Ejection fraction (EF) and regional wall motion (RWM) were assessed by left ventriculography performed on admission and at discharge. RESULTS: The APV at the end of monitoring was greater in group I than in group D. In group I, EF and RWM were significantly improved at discharge. The change in EF was greater in group I than in group D (17 +/- 9% vs. 4 +/- 9%, p = 0.007), as was the change in RWM (0.96 +/- 0.23 vs. 0.13 +/- 0.36 SD/chord, p < 0.0001). CONCLUSIONS: The alteration in flow velocity in recanalized infarcted arteries is related to left ventricular recovery. A progressive decrease in velocity after angioplasty implies no reflow, which is associated with a poor recovery of left ventricular function. Reperfusion injury may account in part for this phenomenon.     

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.     

Regional wall motion changes with dobutamine as a pharmacological stress test during cardiac catheterization in patients with significant coronary artery disease

BACKGROUND: Preliminary study to test the feasibility of pharmacological stress testing during cardiac catheterization, thus combining anatomical and functional information. PATIENTS AND METHODS: 21 consecutive patients with known or suspected coronary artery disease, referred for diagnostic catheterization. Biplane ventriculography was performed before and during dobutamine infusion. The patients were subdivided into 3 groups: Group I (n = 11, 52%) with at least one territory supplied by a significantly stenosed coronary artery and showing normal resting regional wall motion. Group II (n = 6, 29%) patients in whom the affected vessel(s) supplied exclusively a territory with regional wall motion abnormalities at rest. Group III (n = 4, 19%) had no significant coronary artery disease and served as control. RESULTS: In group I, 9/11 (82%) patients and in group II, 3/6 (50%) patients showed either ischemia or viability reactions or both after dobutamine stress. Overall, substantial functional information was gathered in 12/17 patients (71%). Control patients showed no worsening of regional wall motion under dobutamine. Neither global left ventricular ejection fraction nor left ventricular end diastolic pressure were as accurate in detecting ischemia as regional wall motion analysis. In patients who had only ischemia and no viability reaction as judged by regional wall motion analysis, ejection fraction fell significantly in 4/6 (67%) patients; end diastolic pressure on the other hand rose significantly in 3/6 (50%). CONCLUSIONS: Dobutamine stress testing performed during cardiac catheterization is convenient, feasible and safe and yields clinically useful information in a high percentage (71%) of patients with significant coronary artery disease. Further experience is needed to evaluate the sensitivity, specificity and predictive value of this new approach.     

The effect of blood viscoelasticity on pulsatile flow in stationary and axially moving tubes

An analytical solution for pulsatile flow of a generalized Maxwell fluid in straight rigid tubes, with and without axial vessel motion, has been used to calculate the effect of blood viscoelasticity on velocity profiles and shear stress in flows representative of those in the large arteries. Measured bulk flow rate Q waveforms were used as starting points in the calculations for the aorta and femoral arteries, from which axial pressure gradient delta P waves were derived that would reproduce the starting Q waves for viscoelastic flow. The delta P waves were then used to calculate velocity profiles for both viscoelastic and purely viscous flow. For the coronary artery, published delta P and axial vessel acceleration waveforms were used in a similar procedure to determine the separate and combined influences of viscoelasticity and vessel motion. Differences in local velocities, comparing viscous flow to viscoelastic flow, were in all cases less than about 2% of the peak local velocity. Differences in peak wall shear stress were less than about 3%. In the coronary artery, wall shear stress differences between viscous and viscoelastic flow were small, regardless of whether axial vessel motion was included. The shape of the wall shear stress waveform and its difference, however, changed dramatically between the stationary and moving vessel cases. The peaks in wall shear stress difference corresponded with large temporal gradients in the combined driving force for the flow.     

Resection of the metatarsal head for diabetic foot ulcers

Dobutamine-induced hypotension has been disregarded as a marker of more severe functional abnormalities in patients with suspected coronary artery disease. However, its functional significance in patients with myocardial infarction has not been studied. The aim of this study was to define the predictors of systolic blood pressure (SBP) response to dobutamine in patients with previous myocardial infarction. Dobutamine stress (up to 40 microg/kg per minute) echocardiography was performed in 326 patients with prior myocardial infarction referred for evaluation of myocardial ischemia. A 16-segment, four-grade score model was used to assess left ventricular function. Wall motion score index was derived by summation of wall motion score divided by 16. SBP and heart rate increased from rest to peak dobutamine stress (127 +/- 22 vs 134 +/- 27 mm Hg and 72 +/- 14 vs 122 +/- 24 bpm, p < 0.00001 in both). An increase of SBP > or = 30 mm Hg occurred in 50 patients (15%). By multivariate analysis, independent predictors of failure of SBP increase were higher peak wall motion score index (p < 0.001), higher resting SBP (p < 0.01), and medication with calcium channel blockers (p < 0.05). SBP drop > or = 20 mm Hg occurred in 54 patients (17%). Independent predictors of SBP drop were higher resting wall motion score index (p < 0.001), higher resting SBP (p < 0.0001), and older age (p < 0.05). In patients with myocardial infarction, left ventricular function and baseline systolic blood pressure are powerful predictors of SBP response to dobutamine stress testing.     

Sex and crime: heterotrimeric G proteins in fungal mating and pathogenesis

The coronary circulation is the major determinant of myocardial oxygen balance which in turn is necessary for adequate cardiac function under a variety of conditions. Experiments in the fetal lamb suggest short-term functional coronary autoregulation in response to increase in afterload and acute hypoxemia. Long-term, acute-on-chronic hypoxemia is associated with a marked increase of maximal myocardial flow reserve suggesting coronary vascular angio-neogenesis during the period of chronic hypoxemia. In the human fetus, flow velocity waveforms from the coronary arteries may be obtained by color-coded and pulsed wave Doppler sonography in normally developed fetuses from 31 weeks of gestation onwards under favorable imaging conditions. Coronary blood flow may also be visualized in selected fetuses with intrauterine growth restriction, absent or reversed end-diastolic flow in the umbilical artery, cephalization of blood flow and abnormal flow patterns in the precordial veins and the umbilical vein. In these fetuses visualization of coronary blood flow may be possible as early as 26 weeks gestation and is consistently associated with a significant increase in the peak velocity index for veins in the ductus venosus. In this circulatory state, visualization of coronary blood flow is suddenly very easy. This "visualization threshold" may be a sign of maximal increase in coronary blood flow in an attempt to "spare" the fetal heart of hypoxemia. Although highly operator dependent, demonstration of coronary blood flow in intrauterine growth restriction identifies fetuses at high risk for intrauterine fetal death and postpartum circulatory failure.