Overexpression, purification, and characterization of the cloned metallo-beta-lactamase L1 from Stenotrophomonas maltophilia

OBJECTIVES: The purpose of this study was to assess whether the presence or absence of myocardial viability during dobutamine echocardiography (DE) predicts survival in patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction. BACKGROUND: In patients with CAD, the presence of myocardial viability during DE identifies viable myocardium and predicts recovery of LV systolic function after revascularization. However, there is little data on the relation between myocardial viability and clinical outcome in patients with CAD and severe LV dysfunction. METHODS: We studied 318 patients with CAD and a LV ejection fraction (EF) < or =35% who underwent DE and were followed for 18+/-10 months. Patients were classified into four groups. Group I (n=85) consisted of patients who had evidence of myocardial viability and subsequently underwent revascularization. Group II (n=119) consisted of patients with myocardial viability who did not undergo revascularization. Group III (n=30) consisted of patients who did not have myocardial viability and underwent revascularization. Finally, group IV (n=84) patients lacked myocardial viability and did not undergo revascularization. RESULTS: The four groups had similar baseline characteristics and rest LVEF. During follow-up there were 51 deaths (16%). The mortality rate was 6% in group I, 20% in group II, 17% in group III and 20% in group TV (p=0.01, group I vs. other groups). CONCLUSIONS: In patients with CAD and severe LV dysfunction who demonstrated myocardial viability during DE, revascularization improved survival compared with medical therapy.     

Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts

OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.     

Two types of fetishism

OBJECTIVE: To evaluate the effects of myocardial viability assessment with positron emission tomography on cardiac revascularization decision-making and consequential outcomes of patients with multivessel coronary artery disease. METHODS: Thirty-three patients with multivessel coronary disease and heart failure were studied in this series, using 13NH for myocardial perfusion and F-18-deoxy-glucose for myocardial metabolism. Viable myocardium (mis-matched perfusion-metabolism) was visually and quantitatively analyzed in anterior, apical, septal, inferior, and lateral segments of the left ventricle. Left ventricular ejection fraction (LVEF) was also measured with first-pass radionuclide angiocardiography. RESULTS: Based on the assessment of myocardial viability, 19 patients (group A) with sufficient viable myocardium underwent revascularization (coronary bypass graft and/or angioplasty), and 14 patients (group B) without sufficient viable myocardium received conservative medical treatment. During an average of 17-month follow-up, there were 2 (10.5%) deaths in group A and 2 in group B (14.3%) deaths (P > 0.5). Patients with revascularization showed significantly improved average LVEFs post-revascularization, without revascularization procedure-related mortality; patients with medical treatment had an initial average LVEF of 25% and class II-III (NYHA) average cardiac function with a survival rate of 86% in average, which was better than that reported in literature. CONCLUSION: Positron emission tomography is useful in myocardial viability assessment for cardiac revascularization decision-making through precisely selecting suitable patients for revascularization and avoiding operations on those who will not benefit, which results in promising effects on outcomes of patients with multivessel coronary disease and severe left ventricular dysfunction.     

Relation of myocardial perfusion at rest and during pharmacologic stress to the PET patterns of tissue viability in patients with severe left ventricular dysfunction

BACKGROUND: Stress perfusion imaging can assess effectively the amount of jeopardized myocardium, but its use for identifying underperfused but viable myocardium has yielded variable results. We evaluated the relation between measurements of myocardial perfusion at rest and during pharmacologic stress and the patterns of tissue viability as determined by positron emission tomographic (PET) imaging. METHODS AND RESULTS: We studied 33 patients with coronary artery disease and left ventricular (LV) dysfunction (LV ejection fraction, 30%+/-8%). PET imaging was used to evaluate regional myocardial perfusion at rest and during pharmacologic stress with [13N]-ammonia as a flow tracer, and to delineate patterns of tissue viability (i.e., perfusion-metabolism mismatch or match) using [18F]-deoxyglucose (FDG). We analyzed 429 myocardial regions, of which 229 were dysfunctional at rest. Of these, 30 had normal perfusion and 199 were hypoperfused. A severe resting defect (deficit >40% below normal) predicted lack of significant tissue viability; 31 of 35 regions (89%) had a PET match pattern denoting transmural fibrosis. Although regions with mild or moderate resting defects (deficit <40% below normal) showed evidence of metabolic activity, perfusion measurements alone failed to identify regions with PET mismatch (reflecting hibernating myocardium). Reversible stress defects were observed with slightly higher frequency in regions with a PET mismatch (10 of 37) than in those with a PET match (36 of 162) pattern of viability. A reversible stress defect was a specific (78%) marker, but was a relatively insensitive marker (27%) of viable myocardium as defined by the PET mismatch pattern. CONCLUSIONS: In patients with LV dysfunction, the severity of regional contractile abnormalities correlates with the severity of flow deficit at rest. Severe reductions in resting blood flow in these dysfunctional regions identify predominantly nonviable myocardium that is unlikely to have improved function after revascularization. Although dysfunctional myocardium with mild to moderate flow reductions contains variable amounts of viable tissue (as assessed by FDG uptake), flow measurements alone do not distinguish between regions with PET mismatch (potentially reversible dysfunction) and PET match (irreversible dysfunction). The presence of an irreversible defect on stress imaging is a relatively specific (78%) marker of PET match, whereas a reversible stress defect is a rather insensitive (27%) marker of viability, as defined by the PET mismatch pattern.     

Preparation of monoclonal antibodies against chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and their effects on enzyme activities

The identification of hibernating myocardium in patients with poor ventricular function has become increasingly important as investigators demonstrate an improvement in ventricular performance in patients with injured but viable myocardium who undergo surgical revascularization. Modifications of 201Tl redistribution protocols and rest/stress 99mTc-labeled hexakis-2-methoxy-2-methyl propylisonitrile perfusion studies continue to underestimate myocardial viability compared with resting 18F-labeled fluorodeoxyglucose (18FDG) positron emission tomography. The combined data from multiple investigators suggest that 18FDG single-photon emission computed tomography used in combination with cardiac perfusion agents, either sequentially or with simultaneous dual-isotope acquisition, may provide an acceptable alternative to positron emission tomographic imaging for the detection of hibernating myocardium.     

Whither paediatric dentistry?

The noninvasive assessment of myocardial viability in patients with coronary artery disease and depressed left ventricular function has proven clinically useful for identifying those patients with ischemic cardiomyopathy who benefit most from coronary revascularization. Thallium-201 (201Tl) imaging at rest has been the radionuclide imaging technique most often utilized for distinguishing viable myocardium from scar. However, new technetium-99m (99mTc) perfusion agents such as 99mTc-sestamibi and 99mTc-tetrofosmin have emerged as alternatives to 201Tl for imaging of regional myocardial perfusion. Whether these new agents, which have better physical properties for imaging with a gamma camera than 201Tl, are valid for use in assessing myocardial viability is still uncertain. Recent clinical studies have demonstrated that these agents, when imaged using quantitative SPECT, can identify patients with myocardial hibernation who exhibit improved regional systolic function following revascularization. Experimental laboratory studies have shown that the uptake of 99mTc-sestamibi and 99mTc-tetrofosmin in ischemic myocardium is only slightly lower than the uptake of 201Tl. These 99mTc-labeled agents remain bound intracellularly in mitochondria of viable myocytes under conditions of myocardial stunning and short-term hibernation, producing severe myocardial asynergy. With respect to determination of viability, the inferior wall region is at times problematic since attenuation of 99mTc-sestamibi and 99mTc-tetrofosmin is greatest in this area. Demonstration of preserved systolic thickening on ECG-gated SPECT images is indicative of viability in the instance of decreased regional 99mTc counts due to attenuation and not scar. Administration of nitrates prior to tracer injection improves the sensitivity for identifying viable myocardial segments using rest imaging with 99mTc-sestamibi or 99mTc-tetrofosmin. Thus, it appears that the new 99mTc perfusion imaging agents can be successfully employed for the determination of myocardial viability in the setting of severe regional dysfunction and chronic coronary artery disease. The greater the myocardial uptake of these agents in the resting state, the greater the probability of improved systolic function after coronary revascularization.     

Myocardial viability. Study of viability by myocardial scintigraphy

FUNDAMENTAL PRINCIPLES: Myocardial scintigraphy is a metabolic approach to myocardial viability visualizing the localization, the extent and to some degree the quantity of non-functional yet viable myocardial tissue. Potential for functional recovery cannot be ascertained directly from the scintigram but can be inferred from commonly observed behavior after blood flow has been restored. Myocardial scintigraphy is thus fundamentally different from other functional exploration methods such as echocardiography or nuclear magnetic resonance imaging which can detect residual contractile capacity unmasked by inotropic stimulation. It must be remembered however that such 'forced' contractility may not necessarily be expresses spontaneously after revascularization and that, however detected, truly viable myocardium may not recover normal contractility after reperfusion when associated with non-transmural infarction or diffuse fibrosis. PET AND THALLIUM 201 SCANS: Positron emission tomography (PET) is the gold standard. Accomplished after administration of an isotope labeled substance (18-fluoro-deoxyglucose, FDG), the PET scan visualizes metabolic activity in viable myocardium. Special equipment is however required and facilities are limited, particularly in France. Thallium 201 scans can be acquired with conventional gamma cameras and protocols have been widely developed with nearly equivalent performance in certain situations of doubtful residual viability after post-infarction thrombolysis or angioplasty. It must be noted however that in such cases, search for homolateral or contralateral ischemia may be the main objective rather than the detection of residual viability. A 3-step thallium 201 scintigraphy protocol with stress, 4-hr redistribution then imaging after reinjection is usually sufficient to document ischemia or viability warranting revascularization. The problem is quite different for patients with major myocardial dysfunction and histological remodeling due to hypokinetic dilated cardiomyopathy. In such types of myocardium, chances of recovering inotropic capacity are quite limited and detecting viable tissue would be technically difficult; however with a proper protocol (without stress, resting images late after injection), thallium 201 scintigraphy can be helpful. PERFORMANCE: Data in the literature shows that isotopic techniques lack specificity by overestimating the extent of viable tissue capable of recovering contractility. Actually this could be seen as an advantage since the consequences of missing even a small chance for revascularization warrant risking an ineffective procedure for a patient whose only alternative is heart transplantation. This situation explains why 18-FDG PET exploration should be performed even if the thallium scintigram leaves very little room for hope of recovering viable myocardium in patients with terminal disease. PERSPECTIVES: Isotopic exploration of the myocardium is a moving field and routine practice can expect to benefit from research conducted in pioneer centers. The future offers two main perspectives: the development of metabolic tracers giving more precision than thallium 201 (for example isotope-labeled fatty acids); and technical advances in conventional gamma cameras more adapted to the physical characteristics of 18 FDG used for PET scans. Scintigraphy is an indispensible tool for metabolic exploration of the myocardium. Only nuclear magnetic resonance spectroscopy may provide comparable results.     

Safety and utility of atropine addition during dobutamine stress echocardiography for the assessment of viable myocardium in patients with severe left ventricular dysfunction

OBJECTIVE: To assess the feasibility safety and side effects of the addition of atropine to dobutamine stress echocardiography for the detection of viable myocardium in patients with left ventricular dysfunction (ejection fraction < or = 35%) prior to coronary revascularization. BACKGROUND: The assessment of viable and/or ischaemic myocardium has high prognostic value as regards improvement of function and survival after coronary revascularization. The addition of atropine to dobutamine during echocardiographic testing for the presence of viable myocardium is not common practice. Consequently, no data exist on the safety and additional diagnostic value of this practice. METHODS: Two hundred patients with left ventricular ejection fraction < or = 35% were studied. RESULTS: Test end-points were: target heart rate in 164 (82%) of the patients, severe angina in 18 (9%), maximum dobutamine-atropine dose in six (3%), severe ST segment changes in five (2%), cardiac arrhythmias in four (2%), and hypotension in three (1%). Viability could be assessed echocardiogaphically in 105/200 (53%) from a biphasic response (improvement of wall motion with low dose dobutamine and worsening with high dose), in 93 from ischaemia and in 12 from sustained or late improvements. In 36/105 (34%) patients, ischaemic myocardium could only be assessed after the addition of atropine. Cardiac arrhythmias occurred in 11/200 (6%) and hypotension (decrease of systolic blood pressure >30 mmHg) in 21/200 (11%). Neither the use of atropine nor the induction of ischaemia were associated with an increased incidence of cardiac arrhythmias or hypotension. CONCLUSIONS: In a large group of patients with severe left ventricular dysfunction, dobutamine stress echocardiography is feasible and safe in 186/200 (93%); the addition of atropine was necessary in 34% to assess myocardial viability. Hypotension and cardiac arrhythmias were the most frequent side effects, but were not related to the induction of ischaemia or addition of atropine.     

Myocardial viability. Myocardial viability post-infarct: contribution of dobutamine-echography

ROUTINE EXPLORATION: Echocardiography during dopamine perfusion has been widely proven as an effective tool for determining myocardial viability. Dobutamine has marketing authorization in France for stress-echocardiography and is widely used in clinical practice outside research protocols. The exploration must however be conducted within an appropriately equipped cardiac intensive care unit. Stress-echocardiography has certain advantages over isotropic techniques, in terms of equipment costs, examination time and exposure to isotopes. POST-INFARCTION: Dobutamine-echocardiography enables detection of viable myocardium within the infarct zone, evaluates the degree of residual ischemia in the infarct zone and provides information on prognosis. It would not however be reasonable to perform stress-echocardiography as a first line exploration after infarction. International guidelines recommend a sub-maximal ECG exercise test prior to coronarography. The contribution of stress-echocardiography after infarction is its ability to give precise information on myocardial viability and residual ischemia in one or more territories to compare with coronary lesions, thus allowing indication for revascularization. CHRONIC ISCHEMIC CARDIOPATHY: Dobutamine-echocardiography can be used to detect hibernating myocardium in patients with chronic ischemic cardiopathy. In this indication, the sensitivity of stress-echocardiography is slightly lower than thallium scintigraphy, but its specificity and positive predictive values are higher. The best predictive value is obtained with bimodal dobutamine-echocardiography: improve-med thickening at low doses and a degradation at high dose is predictive of functional improvement after revascularization in 72% of the cases. In more severe cases with ejection fraction < 35%, improvement in hibernating myocardium after revascularization leads to a significant improvement in left ventricular ejection fraction.     

Children''s spiritual response: validation of the nursing diagnosis spiritual distress

A variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. This review will introduce these new techniques which have recently been available in Japan. Tc-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use of first-pass angiography or ECG-gated acquisition. Positron emission tomography enables metabolic assessment in vivo. Preserved FDG uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently I-123 BMIPP, a branched fatty acid analog, has been clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. Such perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Both of them are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. I-123 MIBG uptake in the myocardium reflects adrenergic neuronal function in vivo. In the study of coronary artery disease, neuronal denervation is often observed around the infarcted myocardium and post ischemic region as well. More importantly, reduced MIBG uptake in these patients can identify high risk for ventricular arrhythmias and assess severity of congestive heart failure. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment in these patients.     

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.     

PET scan predicts recovery of left ventricular function after coronary artery bypass operation

BACKGROUND: Viable but hypocontractile myocardium can show functional improvement after revascularization (hibernation). It is sometimes difficult, however, to predict viability and recovery in patients with severe left ventricular function. This study sought to identify possible predictive factors of recovery of cardiac function after revascularization in patients with three-vessel disease. METHODS: Positron emission tomography (fluoro-18-deoxyglucose uptake for metabolism; nitrogen 13-labeled ammonia for flow) and equilibrium-gated nuclear angiography (for the global ejection fraction) were performed in 59 patients with three-vessel disease before and after undergoing coronary artery bypass grafting. The positron emission tomographic data were expressed as match normal (flow and metabolism normal), mismatch (low flow, high metabolism), match viable (moderate decrease in flow and metabolism), and match necrosis (low flow and metabolism). RESULTS: Stepwise logistic regression analysis showed that only mismatch regions played a significant role in predicting postoperative improvement in function (p = 0.019). There were 1.7 +/- 1.5 mismatch regions in 31 patients who showed an improvement in their ejection fraction (0.47 +/- 0.14 versus 0.58 +/- 0.11; mean +/- standard deviation) versus 0.8 +/- 1.0 mismatch regions (p = 0.017) in patients who did not show recovery. There was more pronounced functional improvement with increasing numbers of mismatch regions, and patients with at least one mismatch region had a high likelihood of recovery (p < 0.001). In patients with a very low preoperative ejection fraction and two or more mismatch regions, there was early significant recovery (0.27 +/- 0.08 versus 0.46 +/- 0.06; p = 0.009). CONCLUSIONS: At least one mismatch region must be present for there to be a postoperative functional benefit. When a low left ventricular ejection fraction is associated with mismatch, early recovery is substantial.     

Paradigms and expectations: the nature of research and diagnostics

OBJECTIVES: Our purpose was to evaluate the long-term benefit of myocardial viability assessment for stratifying risk and selecting patients with low ejection fraction for coronary artery bypass grafting and to determine the relation between the severity of anginal symptoms, the amount of ischemic myocardium, and clinical outcome. METHODS: We studied 93 consecutive patients with severe coronary artery disease and low ejection fraction (median, 25%) who underwent positron emission tomography to delineate the extent of perfusion-metabolism mismatch (reflecting hibernating myocardium) for potential myocardial revascularization. Median follow-up was 4 years (range, 0 to 6.2 years). RESULTS: Fifty patients received medical therapy, and 43 patients underwent bypass grafting. In Cox survival models, heart failure class, prior myocardial infarction, and positron emission tomographic mismatch were the best predictors of survival. Patients with positron emission tomographic mismatch receiving bypass grafting had improved 4-year survival compared with those on medical therapy (75% versus 30%; P =.007) and a significant improvement in angina and heart failure symptoms. In patients without positron emission tomographic mismatch, bypass grafting tended to improve survival and symptoms only in those patients with severe angina (100% versus 60%; P =.085), whereas no survival advantage was apparent in patients with minimal or no anginal symptoms (63% versus 52%; P =.462). CONCLUSIONS: Patients with low ejection fraction and evidence of viable myocardium by positron emission tomography have improved survival and symptoms with coronary bypass grafting compared with medical therapy. In patients without evidence of viability, survival and symptom improvement with bypass grafting are apparent only among those patients with severe angina.     

Fluorine-18-fluorodeoxyglucose cardiac imaging using a modified scintillation camera

Conventional 201TI and hexakis 2-methoxy-2-isobutyl isonitrile studies are less accurate as compared to FDG PET in the prediction of functional recovery after revascularization in patients with injured but viable myocardium. The introduction of a dual-head variable-angle-geometry scintillation camera equipped with thicker crystals (5/8 in.) and high-resolution, ultrahigh-energy collimators capable of 511 keV imaging has permitted FDG SPECT to provide information equivalent to that of PET for the detection of injured but viable myocardium in patients with chronic ischemic heart disease. The development of standardized glucose-loading protocols, including glucose-insulin-potassium infusion and the potential use of nicotinic acid derivatives, has simplified the method of obtaining consistently good-to-excellent quality FDG SPECT cardiac studies. FDG SPECT may become the modality of choice for evaluating injured but viable myocardium because of enhanced availability of FDG, logistics, patient convenience, accuracy and cost-effectiveness compared to PET.     

Assessment of hibernating myocardium by dobutamine stimulation in a canine model

OBJECTIVES: The purpose of this study was to 1) develop an animal model of hibernating myocardium, and 2) evaluate the ability of dobutamine stimulation to detect hibernating myocardium using both qualitative and quantitative assessment of regional myocardial function. BACKGROUND: Left ventricular dysfunction may be due to chronic ischemia with or without myocardial infarction and may improve after coronary blood flow is enhanced by revascularization procedures. This condition has been coined "hibernating myocardium" and variably defined in recent years. The results of recent clinical studies suggest that dobutamine echocardiography may be useful for detecting viable myocardium in patients with left ventricular dysfunction. METHODS: Twenty-one dogs underwent initial operation. Sonomicrometer crystals were implanted, and baseline measurements of segment shortening and wall thickening (by echocardiography) were made. A coronary artery was ligated; the chest was closed; and measurements were repeated. Dobutamine was incrementally infused with determination of wall thickening and segment shortening at baseline and on days 3 and 7 and weeks 2 and 4 after coronary artery occlusion. Finally, the chest was reopened; the ligated vessel was bypassed; and measurements were repeated. RESULTS: Of the 10 dogs that completed the entire protocol, 7 had varying degrees of nontransmural myocardial infarction (group 1), and 3 had complete transmural myocardial infarction (group 2). In group 1, baseline function was significantly impaired compared with preligation function but increased during dobutamine infusion. When reperfused after 4 weeks, both wall thickening and segment shortening increased significantly. In group 2, significant changes were not seen during the dobutamine studies or after reperfusion. Myocardial perfusion during dobutamine infusion increased in group 1 but did not change in group 2. CONCLUSIONS: We demonstrated improvement in chronically dysfunctional myocardium after restoration of previously interrupted myocardial blood flow in dogs after nontransmural myocardial infarction, thus validating a canine model of hibernating myocardium. As assessed by two independent methods, dobutamine infusion identified hibernating myocardium in an animal model.     

Treatment of pathological fractures of the humeral shaft due to bone metastases: a comparison of intramedullary locking nail and plate osteosynthesis with adjunctive bone cement

The assessment of myocardial viability is of increasing clinical relevance in the era of thrombolytic therapy and coronary revascularization. Dobutamine stress echocardiography has been proposed as a method of detecting residual viability. The echocardiographic hallmark for viability of a dyssynergic segment is improvement of wall thickening after inotropic challenge. Several clinical studies published over the past year have shown the value of dobutamine stress echocardiography in predicting improvement in regional and global ventricular function after revascularization.     

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.     

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells

OBJECTIVES: To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class > or = III) with and without angina. METHODS: Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. RESULTS: A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% +/- 7% to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. CONCLUSIONS: In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization.     

Endothelin-1 enhances thymocyte proliferation in monolaterally adrenalectomized rats with contralateral adrenocortical regeneration

BACKGROUND: Transmyocardial laser revascularization has been used to treat patients with end-stage coronary artery disease that is not amenable to standard revascularization. Although there is evidence of angina relief and quality of life enhancement, there is little information concerning improvement in myocardial contractility. The purpose of this study was to determine whether transmyocardial laser revascularization improves myocardial function in chronically ischemic myocardium. METHODS: In a model of chronic ischemia by Ameroid occlusion of the circumflex artery, domestic pigs (n = 8) were treated with transmyocardial laser revascularization. Before laser treatment, segmental contraction was assessed at rest and with dobutamine stress echocardiography. Myocardium subtended by the occlusion was compared with that remote from the occlusion. Six weeks after transmyocardial laser revascularization, the animals were restudied at rest and with stress, and then sacrificed. Sham-treated control animals (n = 4) underwent the same procedures but were not treated with transmyocardial laser revascularization. Control animals did not demonstrate significant recovery of function. RESULTS: Transmyocardial laser revascularization improved resting function in chronically ischemic myocardium by 100%. CONCLUSIONS: Transmyocardial laser revascularization significantly improves the function of chronically ischemic myocardium. These data may help explain the mechanisms by which transmyocardial laser revascularization is clinically effective.     

Improved outcome after coronary bypass surgery in patients with ischemic cardiomyopathy and residual myocardial viability

BACKGROUND: Although residual myocardial viability in patients with coronary artery disease and extensive regional asynergy is associated with improved ventricular function after coronary bypass surgery, the relationship between viability and clinical outcome after surgery is unclear. We hypothesized that patients with poor ventricular function and predominantly viable myocardium have a better outcome after bypass surgery compared with those with less viability. METHODS AND RESULTS: Seventy patients with multivessel coronary artery disease and left ventricular ejection fractions < 40% who underwent preoperative quantitative 201Tl scintigraphy before coronary bypass surgery were analyzed retrospectively. 201Tl scintigrams were reviewed blindly, and each segment was assigned a score based on defect magnitude. Segmental viability scores were summed and divided by the number of segments visualized to determine a viability index. The viability index was significantly related to 3-year survival free of cardiac event (cardiac death or heart transplant) after bypass surgery (P=.011) and was independent of age, ejection fraction, and number of diseased coronary vessels. Patients with greater viability (group 1; viability index > 0.67; n=33) were similar to patients with less viability (group 2; viability index < or = 0.67; n=37) with respect to age, comorbidities, and extent of coronary artery disease. There were 6 cardiac deaths and no heart transplants in group 1 patients and 15 cardiac deaths and two transplants in group 2 patients. Survival free of cardiac death or transplantation was significantly better in group 1 patients on Kaplan-Meier analysis (P=.018). CONCLUSIONS: We conclude that resting 201Tl scintigraphy may be useful in preoperative risk stratification for identification of patients more likely to benefit from surgical revascularization.