Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2.

The discovery of microRNA (miR) represents a novel paradigm in RNA-based regulation of gene expression and their dysregulation has become a hallmark of many a tumor. In virally associated cancers, the host-pathogen interaction could involve alteration in miR expression. Epstein-Barr virus (EBV)-encoded EBNA2 is indispensable for the capacity of the virus to transform B cells in vitro. Here, we studied how it affects cellular miRs. Extensive miR profiling of the virus-infected and EBNA2-transfected B lymphoma cells revealed that oncomiR miR-21 is positively regulated by this viral protein. Conversely, Burkitt's lymphoma (BL) cell lines infected with EBNA2 lacking P3HR1 strain did not show any increase in miR-21. EBNA2 increased phosphorylation of AKT and this was directly correlated with increased miR-21. In contrast, miR-146a was downregulated by EBNA2 in B lymphoma cells. Low miR-146a expression correlates with an elevated level of IRAK1 and type I interferon in EBNA2 transfectants. Taken together, the present data suggest that EBNA2 might contribute to EBV-induced B-cell transformation by altering miR expression and in particular by increasing oncomiR-like miR-21 and by affecting the antiviral responses of the innate immune system through downregulation of its key regulator miR-146a.

Pre-discharge stress echocardiography and exercise ECG for risk stratification after uncomplicated acute myocardial infarction: results of the COSTAMI-II (cost of strategies after myocardial infarction) trial.

OBJECTIVE: To compare in a prospective, randomised, multicentre trial the relative merits of pre-discharge exercise ECG and early pharmacological stress echocardiography concerning risk stratification and costs of treating patients with uncomplicated acute myocardial infarction. DESIGN: 262 patients from six participating centres with a recent uncomplicated myocardial infarction were randomly assigned to early (day 3-5) pharmacological stress echocardiography (n = 132) or conventional pre-discharge (day 7-9) maximum symptom limited exercise ECG (n = 130). RESULTS: No complication occurred during either stress echocardiography or exercise ECG. At one year follow up there were 26 events (1 death, 5 non-fatal reinfarctions, 20 patients with unstable angina requiring hospitalisation) in patients randomly assigned to early stress echocardiography and 18 events (2 reinfarctions, 16 unstable angina requiring hospitalisation) in the group randomly assigned to exercise ECG (not significant). The negative predictive value was 92% for stress echocardiography and 88% for exercise ECG (not significant). Total costs of the two strategies were similar (not significant). CONCLUSION: Early pharmacological stress echocardiography and conventional pre-discharge symptom limited exercise ECG have similar clinical outcome and costs after uncomplicated infarction. Early pharmacological stress echocardiography should be considered a valid alternative even for patients with interpretable baseline ECG who can exercise.

Coronary blood flow, metabolism, and function in dysfunctional viable myocardium before and early after surgical revascularisation.

OBJECTIVES: To assess the link between perfusion, metabolism, and function in viable myocardium before and early after surgical revascularisation. DESIGN: Myocardial blood flow (MBF, thermodilution technique), metabolism (lactate, glucose, and free fatty acid extraction and fluxes), and function (transoesophageal echocardiography) were assessed in patients with critical stenosis of the left anterior descending coronary artery (LAD) before and 30 minutes after surgical revascularisation. SETTING: Tertiary cardiac centre. PATIENTS: 23 patients (mean (SEM) age 57 (1.7) years with LAD stenosis: 17 had dysfunctional viable myocardium in the LAD territory, as shown by thallium-201 rest redistribution and dobutamine stress echocardiography (group 1), and six had normally contracting myocardium (group 2). RESULTS: LAD MBF was lower in group 1 than in group 2 (58 (7) v 113 (21) ml/min, p < 0.001) before revascularisation and improved postoperatively in group 1 (129 (133) ml/min, p < 0.001) but not in group 2 (105 (20) ml/min, p = 0.26). Group 1 also had functional improvement in the LAD territory at intraoperative echocardiography (mean regional wall motion score from 2.6 (0.85) to 1.5 (0.98), p < 0.01). Oxidative metabolism, with lactate and free fatty acid extraction, was found preoperatively and postoperatively in both groups; however, lactate and free fatty acid uptake increased after revascularisation only in group 1. CONCLUSIONS: MBF is reduced and oxidative metabolism is preserved at rest in dysfunctional but viable myocardium. Surgical revascularisation yields immediate perfusion and functional improvement, and increases the uptake of lactate and free fatty acids.

Influence of contractile reserve and inducible ischaemia on left ventricular remodelling after acute myocardial infarction.

OBJECTIVE: To assess the relative influence of contractile reserve and inducible ischaemia on subsequent left ventricular volume changes after myocardial infarction. DESIGN: Left ventricular end diastolic and end systolic index volumes were calculated prospectively at discharge and at six months in 143 patients referred for early postinfarction dobutamine stress echocardiography. On the basis of their responses to this test, patients were divided into three groups: scar (n = 48; group 1); contractile reserve (n = 36; group 2); inducible ischaemia (n = 59; group 3). RESULTS: At six months, the left ventricular end diastolic index volume decreased in group 2 (mean (SD), -3.9 (9.4) ml/m2) and increased in both group 1 (+2.8 (10.6) ml/m2, p = 0.009 v group 2) and group 3 (+7.5 (11.4) ml/m2, p < 0.0001 v group 2). The end systolic index volume decreased in group 2 (-4.9 (7.3) ml/m2) and increased in both group 1 (+1.3 (8.3) ml/m2, p = 0.0015 v group 2) and group 3 (+2.8 (8.9) ml/m2, p = 0.0002 v group 2). In multivariate analysis, the contractile reserve (hazard ratio 0.19, 95% confidence interval (CI) 0.14 to 0.47), inducible ischaemia (5.86, 95% CI 1.54 to 29.7), and end systolic index volume at discharge (1.04, 95% CI 0.99 to 1.11) were independent predictors of an increase in end diastolic index volume of > or = 15 ml/m2 at six months. CONCLUSIONS: Contractile reserve and inducible ischaemia, as detected by early dobutamine stress echocardiography, identify patients with differences in long term left ventricular remodelling after acute myocardial infarction.

Prognostic and clinical correlates of angiographically diffuse non-obstructive coronary lesions.

OBJECTIVE: To make a prospective assessment of the clinical and prognostic correlates of angiographically diffuse non-obstructive coronary lesions. DESIGN: Angiographic vessel and extent scores were calculated in 228 clinically stable patients (mean (SD) age, 60 (11) years; 43 women, 185 men) undergoing prospective follow up for the composite end point of death and myocardial infarction. The effect on outcome of clinical variables (age, sex, previous myocardial infarction, diabetes mellitus, smoking habit, systemic hypertension, hypercholesterolaemia, ejection fraction) and angiographic variables (vessel and extent score) was evaluated by Cox's proportion hazard model. RESULTS: The vessel score was 3 in 34 patients (15%), 2 in 78 (34%), 1 in 87 (38%), and 0 in 29 (13%). Median extent score was 60 (range 6-110; first quartile 40, third quartile 70). Forty one events (nine deaths and 32 myocardial infarcts) occurred over a median follow up period of 30 months. Age and extent score were the only multivariate predictors of outcome, but the latter provided 28% additional prognostic information after adjustment for the most predictive variables (gain in chi2 = 7, p < 0.01). A vessel score of 3 was associated with worse survival, while no significant discrimination was possible among the other groups. However, assignment of patients to two groups according to an ROC curve derived cut off value for the extent score made it possible to obtain significant discrimination of survival even in cases with vessel scores of 0 to 2. Age and diabetes were clinical markers of a higher extent score. CONCLUSIONS: The angiographic extent score is a powerful marker of adverse outcome independent of severity and the number of flow limiting coronary lesions, and may reflect the link between clinical risk profile and diffusion of coronary atherosclerosis. Thus it should be of clinical value for targeting aggressive preventive measures.

Infection by Helicobacter pylori and acute myocardial infarction. Do cytotoxic strains make a difference?

The classical risk factors for acute myocardial infarction (AMI) fail to explain all the epidemiological variations of the disease. Among the risk factors recently reported, several infectious agents appear to increase the risk of AMI. Helicobacter pylori (H. pylori) infection, a bacterium involved in duodenal and gastric ulcer, gastric cancer and MALT-lymphoma, seems to be strongly associated with AMI. More virulent (anti-CagA positive) strains of the bacterium are almost exclusively the causative agents of such diseases. To determine the prevalence of H. pylori infection and of virulent strains, a case-control study was conducted in a group of male patients with AMI. A group of patients consecutively admitted to the Emergency Care Unit served as controls. We studied 223 consecutive male patients, mean age 60.2 (range 40-79) years, admitted for AMI to the Coronary Care Units at Hospitals in two towns of Northern Italy, 223 age matched male patients (mean age 61.8, range 40-79 years) admitted to the Emergency Care Unit, served as control. H. pylori seroprevalence was assessed by presence of antibodies (IgG) against H. pylori and anti-CagA in circulation. Among the patients we investigated the presence of hypertension, levels of cholesterol and glucose in serum, fibrinogen in plasma and smoking habits. H. pylori infection was present in 189/223 (84.7%) of the patients and in 138/223 (61.8%) of the control population (p < 0.0001 OR 3.42 [IC 95% 2.12-5.54]). The anti-CagA antibodies were detected in 33.8% of infected patients with AMI (64/189) versus 26.8% in the control subjects (37/138) (p:0.17, OR 1.40 [IC 95% 0.84-2.33]). Classical risk factors for AMI did not differ among patients with and without H. pylori infection. Patients admitted to the Coronary Care Unit for acute myocardial infarction had a notably higher prevalence of anti-H. pylori not restricted to virulent strains, when compared to a population of patients referred to the Emergency Care Unit. The classical risk factors for coronary disease were present in the patients with AMI irrespective of H. pylori status.

Unfavourable left ventricular remodelling in patients with dobutamine-inducible ischaemia after acute myocardial infarction.

AIMS: Aim of the study was to assess the role of early inducible ischaemia for determining left ventricular remodelling in patients with acute myocardial infarction. METHODS AND RESULTS: In 179 consecutive patients with first myocardial infarction the occurrence of new wall motion abnormalities during dobutamine stress echocardiography at discharge was related to the left ventricular volume changes at 6 months. Left ventricular end-diastolic and end-systolic index volumes (mL/m(2)) were echocardiographically detected at discharge and at 6 months and the relative changes were calculated. The study population consisted of 105 patients without and 74 patients with inducible ischaemia; of these, 46 patients had > or =4 ischaemic segments. At 6 months, the end-diastolic index volume increased in patients with inducible ischaemia compared to patients without (+7.5+/-11.2 vs -0.1+/-10.2 mL/m(2); P=0.0049) and final mean end-diastolic volume was greater in patients with inducible ischaemia than without (70.8+/-16.0 vs 61.1+/-17.0 mL/m(2); P=0.0012). The end-systolic volume increased at 6 months in patients with inducible ischaemia and it decreased in patients without (+2.8+/-8.6 vs -1.4+/-7.8 mL/m(2); P=0.021). At the multivariate analysis, inducible ischaemia in > or =4 segments (odds ratio=6.43), the wall motion score index at the peak of dobutamine infusion (odds ratio=1.14) and the end-systolic index volume at discharge (odds ratio=1.06) were independent predictors of subsequent left ventricular end-diastolic index volume increase > or =15 mL/m(2). CONCLUSION: In patients with first myocardial infarction the presence and the severity of inducible ischaemia, as detected by dobutamine stress echocardiography at discharge, indicates an unfavourable left ventricular remodelling.

Clinical and angiographic correlates of dobutamine-induced wall motion patterns after myocardial infarction.

The ability of different dobutamine-induced wall motion patterns to define the anatomic status of the infarct-related artery (IRA) was evaluated in 159 patients who underwent dobutamine stress echocardiography (DSE) and coronary angiography 10 +/- 2 and 18 +/- 3 days, respectively, after hospital admission. The DSE result was classified as: (1) biphasic: improvement with a low dose followed by deterioration with a high dose; (2) worsening: direct deterioration at low or high doses; (3) sustained improvement: improvement with a low dose that was maintained at high dose; and (4) no change: no change during the entire protocol. A diameter narrowing >70% (50% for the left main stem) of major coronary arteries indicated a severe lesion. Angiograms were classified according to the jeopardy score and collateral circulation graded according to Rentrop's classification. DSE was positive in 92 patients (22 had biphasic results and 70 had worsening results) and negative in 67 patients (14 had sustained improvement and 53 had no changes). Biphasic response was associated with more frequent anterior infarction (p <0.05) and higher resting (p <0.001) and peak (p <0.01) wall motion score indexes. The IRA was totally occluded in 4 of the 92 patients (4%) with positive (worsening pattern) and 12 of the 67 patients (18%) with negative (no change pattern) tests. The biphasic pattern was associated with the highest jeopardy score and was significantly (p <0.05) more specific (100%) compared with worsening (78%) in identifying a severe stenosis of the IRA. The combination of ischemic patterns provided a significantly superior sensitivity (p <0.0001). Logistic regression analysis identified the biphasic pattern as the only significant predictor. Conversely, the prediction of total occlusion of the IRA was poor. Sustained improvement was the most specific (100%) predictor of absence of severe stenosis of the IRA, whereas the combination with no change pattern provided a significantly superior sensitivity (p <0.0001). Thus, DSE effectively predicts the residual stenosis of the IRA. In particular, the biphasic response has an excellent specificity and positive predictive value and is the only significant predictor among clinical and echocardiographic variables.

Angiographic and prognostic correlates of cardiac output by cardiopulmonary exercise testing in patients with anterior myocardial infarction.

STUDY OBJECTIVE: To assess the diagnostic and prognostic value of cardiac output assessed by cardiopulmonary exercise testing in patients with anterior acute myocardial infarction (AMI) and left ventricular dysfunction. PATIENTS AND SETTING: Forty-six patients with AMI (7 female patients; mean +/- SD age, 55 +/- 8 years; ejection fraction, 39 +/- 7%) underwent cardiopulmonary exercise testing and coronary angiography following hospital discharge. MEASUREMENT AND RESULTS: Cardiac output was estimated from oxygen uptake (VO(2)) during exercise according to a method based on the linear regression between arteriovenous oxygen content difference and percent maximum VO(2). Angiograms were scored using Gensini and Duke "jeopardy" scores. Cardiac output at anaerobic threshold (COAT) < or = 7.3 L/min was the best cutoff value for identifying multivessel coronary artery disease (relative risk, 3.1). Angiographic scores were significantly higher in patients with COAT < 7.3 L/min as compared to those with COAT > 7.3 L/min (82 +/- 8 vs 53 +/- 7 and 6 +/- 2 vs 4 +/- 3, respectively; p < 0.05) and were inversely and significantly correlated to COAT. Conversely, no correlation was found with ECG changes. COAT, VO(2) at anaerobic threshold, and peak VO(2) were univariate prognostic indicators. However, using Cox's model, COAT was the only multivariate predictor of outcome (odds ratio, 0.28; 95% confidence interval [CI], 0.09 to 0.9). Moreover, COAT < 7.3 L/min was associated to an increased risk of further cardiac events (odds ratio, 5; 95% CI, 1.4 to 17) and provided a significant discrimination of survival for the combined end point of cardiac death, reinfarction, and clinically driven revascularization. CONCLUSIONS: COAT is a safe and feasible tool providing additional diagnostic and prognostic information in patients with AMI.

Stress echocardiography for risk stratification of diabetic patients with known or suspected coronary artery disease.

OBJECTIVE: Coronary artery disease (CAD) is a leading cause of mortality and morbidity in diabetic patients; therefore, their risk stratification is a relevant issue. Because exercise tolerance is frequently impaired in these patients, pharmacological stress echocardiography (SE) has been suggested as a valuable alternative. Our aim was to evaluate the prognostic value of this technique in diabetic patients with known or suspected CAD. RESEARCH DESIGN AND METHODS: A total of 259 consecutive diabetic patients underwent pharmacological SE (dobutamine in 108 patients and dipyridamole in 151 patients) and follow-up for 24 +/- 22 months. A comparison between the prognostic value of SE and exercise electrocardiography (ECG) was made in a subgroup of 120 subjects. RESULTS: A total of 13 cardiac deaths and 13 nonfatal infarctions occurred during follow-up, and 58 patients were revascularized. Univariate predictors of outcome were known CAD, positive SE, rest and peak wall motion score index (WMSI), and peak/rest WMSI variation. Peak WMSI was the only significant and independent prognostic indicator (odds ratio 11; 95% CI 4-29, P < 0.0001) on multivariate Cox's analysis. After adjustment for the most predictive clinical and exercise ECG variables, SE provided 43% additional prognostic information (gain in X(2) = 7, P < 0.01). Moreover, positive SE was associated with a significantly lower event-free survival. CONCLUSIONS: SE effectively predicts cardiac events in diabetic patients with known or suspected CAD and adds additional prognostic information as compared with exercise ECG.

The prognostic value of myocardial viability recognized by low dose dipyridamole echocardiography in patients with chronic ischaemic left ventricular dysfunction.

AIMS: The aim of this study was to assess the prognostic value of myocardial viability recognized as a contractile response to vasodilator stimulation in patients with left ventricular dysfunction in a large scale, prospective, multicentre, observational study. METHODS AND RESULTS: Three hundred and seven patients (mean age 60 +/- 10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction and severe left ventricular dysfunction (ejection fraction <35%; mean ejection fraction: 28 +/- 7%) were enrolled in the study. Each patient underwent low dose dipyridamole echo (0.28 mg x kg(-1) in 4 min). Myocardial viability was identified as an improvement of >0.20 in the wall motion score index. By selection, all patients were followed up for a median of 36 months. One-hundred and twenty-four were revascularized either by coronary artery bypass grafting (n=83) or coronary angioplasty (n=41). The only end-point analysed was cardiac death. In the revascularized group, cardiac death occurred in one of the 41 patients with and in 16 of the 83 patients without a viable myocardium (2.4% vs 19.3%, P<0.01). Outcome, as estimated by Kaplan-Meier survival, was better for patients with, compared to patients without, a viable myocardium, who underwent coronary revascularization (97.6 vs 77.4%, P=0.01). Using a Cox proportional hazards model, the presence of myocardial viability was shown to exert a protective effect on survival (chi-square 4.6, hazard ratio 0.1, 95% CI 0.01-0.8, P<0.03). The survival rate in medically treated patients was lower than in revascularized patients irrespective of the presence of a viable myocardium (79.7% vs 86.2, P=ns). CONCLUSION: In severe left ventricular ischaemic dysfunction, myocardial viability, as assessed by low dose dipyridamole echo, is associated with improved survival in revascularized patients.

Noninvasive assessment of coronary artery disease: the role of stress echocardiography.

Echocardiography combined with either exercise or pharmacological stress is a widely used method for the noninvasive assessment of coronary artery disease. This is due to the high diagnostic accuracy that does not differ substantially among the various stress modalities. In addition, stress echocardiography has a useful role in risk stratification of patients with known or suspected coronary artery disease. In particular, evidence of inducible ischemia is predictive of an unfavorable outcome, whilst its absence is associated with a very low risk of future cardiac events. These findings have strong implications in clinical decision-making. One of the main characteristics of the echographic marker of ischemia is that it is significantly more specific than the electrocardiographic one. The higher specificity of stress echocardiography translates into increased prognostic value as compared to exercise electrocardiography. Nevertheless, exercise electrocardiography has a very high negative predictive value. Moreover, compared to stress echocardiography it is safer, simpler, less costly and requires no specific competence. Based on these data, exercise electrocardiography remains the cornerstone of the noninvasive evaluation of coronary artery disease. Stress echocardiography, on the other hand, is particularly useful in those cases when exercise electrocardiography is not feasible, non-interpretable (owing to the presence of left bundle branch block or of a pacemaker or of other electrocardiographic baseline abnormalities), or when it gives inconclusive data, or a positive result at an intermediate or high workload (in such cases, precise knowledge of the site and extension of ischemia can be of crucial importance in deciding between conservative and aggressive treatment), as well as in cases in which ischemia during the test is frequently a false positive response, as in hypertensive patients, in women and in all cases of left ventricular hypertrophy.

Acute and chronic effects of cadmium on blood homeostasis of an estuarine crab, Chasmagnathus granulata, and the modifying effect of salinity.

Whole body oxygen consumption and some hemolymph parameters such as pH, partial pressure of gases, level of ions and lactate were measured in the estuarine crab Chasmagnathus granulata after both acute (96 h) and chronic (2 weeks) exposure to cadmium at concentrations ranging from 0.4 to 6.3 mg/l. In all instances, the crabs developed hemolymph acidosis, but no respiratory (increased PCO2) or lactate increases were evident. Hemolymph levels of sodium and calcium were always increased by cadmium exposure. The chronic toxicity of cadmium was enhanced at 12 per mil salinity, even causing a significantly higher mortality in comparison with the higher salinity (30 per mil ) used. A general metabolic arrest took place at 12 per mil salinity in the crabs chronically exposed to cadmium, as indicated by decreases of oxygen consumption and PCO2, an increase of PO2, along with no changes in lactate levels. These imbalances were associated with severe necrosis and telangiectasia in the respiratory gills, probably leading to respiratory impairment and finally histotoxic hypoxia and death of the animals.

Prognostic value of pharmacologic stress echocardiography in patients with left bundle branch block.

PURPOSE: Although coronary artery disease is a frequent cause of left bundle branch block, the prognostic value of myocardial ischemia in patients with this conduction abnormality has not been defined. We investigated the value of pharmacologic stress echocardiography in risk stratification of patients with left bundle branch block. PATIENTS AND METHODS: Three hundred eighty-seven patients [230 men and 157 women, mean (+/- SD) age, 64 +/- 9 years] with complete left bundle branch block on the resting electrocardiogram underwent dobutamine (n = 217) or dipyridamole (n = 170) stress echocardiography to evaluate suspected or known coronary artery disease. A summary wall motion score (on a one to four scale) was calculated. The primary end points were cardiac death and nonfatal myocardial infarction. RESULTS: A positive echocardiographic result (evidence of ischemia) was detected in 109 (28%) patients. During a mean follow-up of 29 +/- 26 months, there were 21 cardiac deaths and 20 myocardial infarctions, 63 patients underwent coronary revascularization, and 1 patient received a heart transplant. In a multivariate analysis, four clinical and echocardiographic variables were associated with increased risk of cardiac death: resting wall motion score index [hazard ratio (HR) = 7.5 per unit; 95% confidence interval (CI), 2.8 to 20; P = 0.001], previous myocardial infarction (HR = 2.9; 95% CI, 1.1 to 7.3; P = 0.02), diabetes (HR = 2.7; 95% CI, 1.1 to 6.6; P = 0.03), and the change in wall motion score index from rest to peak stress (HR = 3.0 per unit; 95% CI, 1.0 to 8.6; P = 0.04). The 5-year survival was 77% in the ischemic group and 92% in the nonischemic group (P = 0.02). Four variables were associated with increased risk of cardiac death or infarction: previous myocardial infarction (HR = 3.4; 95% CI, 1.7 to 6.8; P = 0.0005), diabetes (HR = 2.4; 95% CI, 1.2 to 4.6; P = 0.01), resting wall motion score index (HR = 2.2 per unit; 95% CI, 1.1 to 4.1; P = 0.02), and positive echocardiographic result (HR = 2.2; 95% CI, 1.1 to 4.5; P = 0.03). The 5-year infarction-free survival was 60% in the ischemic group and 87% in the nonischemic group (P < 0.0001). Stress echocardiography significantly improved risk stratification in patients without previous myocardial infarction (P = 0.0001), but not in those with previous myocardial infarction (P = 0.08). In particular, it provided additional value over clinical and resting echocardiographic findings in predicting cardiac events among patients without previous infarction. CONCLUSIONS: Myocardial ischemia during pharmacologic stress echocardiography is a strong prognostic predictor in patients with left bundle branch block, particularly in those without previous myocardial infarction.

Acute and chronic effects of cadmium on blood homeostasis of an estuarine crab, Chasmagnathus granulata, and the modifying effect of salinity

Whole body oxygen consumption and some hemolymph parameters such as pH, partial pressure of gases, level of ions and lactate were measured in the estuarine crab Chasmagnathus granulata after both acute (96 h) and chronic (2 weeks) exposure to cadmium at concentrations ranging from 0.4 to 6.3 mg/l. In all instances, the crabs developed hemolymph acidosis, but no respiratory (increased PCO2) or lactate increases were evident. Hemolymph levels of sodium and calcium were always increased by cadmium exposure. The chronic toxicity of cadmium was enhanced at 12 0/00 salinity, even causing a significantly higher mortality in comparison with the higher salinity (30 0/00) used. A general metabolic arrest took place at 12 0/00 salinity in the crabs chronically exposed to cadmium, as indicated by decreases of oxygen consumption and PCO2, an increase of PO2, along with no changes in lactate levels. These imbalances were associated with severe necrosis and telangiectasia in the respiratory gills, probably leading to respiratory impairment and finally histotoxic hypoxia and death of the animals

Incremental prognostic value of stress echocardiography as an adjunct to exercise electrocardiography after uncomplicated myocardial infarction.

OBJECTIVE: To assess the prognostic value of stress echocardiography as an adjunct to exercise electrocardiography in patients with uncomplicated acute myocardial infarction. DESIGN: 496 patients underwent a maximum exercise ECG and pharmacological stress echocardiography (406 dobutamine and 90 dipyridamole) within 15 days of uncomplicated acute myocardial infarction and were followed for a mean of 25 months (range 1-74 months) for reinfarction, unstable angina, and cardiac death. Patients undergoing revascularisation were omitted. RESULTS: Exercise ECG was positive in 162 patients (32.6%) and low threshold positive (< 100 W) in 91 (18%). Stress echocardiography was positive in 239 patients (48%) (194 with dobutamine and 45 with dipyridamole stress). The agreement between the two tests was 63% (kappa = 0.24, 95% confidence interval 0.15 to 0.33). Sixty nine spontaneous events occurred (14 cardiac deaths, 26 reinfarctions, and 29 with unstable angina requiring hospital admission), and 126 patients underwent revascularisation (39 coronary angioplasty and 87 bypass surgery). By receiver operating characteristic curve analysis, stress echocardiography provided incremental prognostic information compared with clinical data. A low threshold positive exercise ECG was associated with a worse outcome, but there was a fivefold increase in risk in patients with positive stress echocardiography who also had a high threshold (> 100 W) positive exercise ECG. Event-free survival of patients with both tests positive was significantly less than in patients with only one positive test or with both tests negative. CONCLUSIONS: Stress echocardiography provides additional prognostic information after uncomplicated acute myocardial infarction, but the greatest gain is found in patients with a high threshold positive exercise ECG.

[Effectiveness and adequacy of management of acute coronary syndromes]. / Efficacia e appropriatezza nella gestione delle sindromi coronariche acute.

A rational utilization of resources represents a key issue in modern treatment of cardiac patients. The aim of our study was to highlight a few essential aspects for an efficient and appropriate management of patients with an acute coronary syndrome. Clinical evaluation of the patient's risk (i.e. clinical assessment of the probability of developing a cardiac event), incremental value of the chosen test for risk stratification, value of a strategy in modifying outcome and direct determinants of medical cost of the strategy are selected as the main aspects to be considered in order to optimize management of these patients.

Prognostic interaction between viability and residual myocardial ischemia by dobutamine stress echocardiography in patients with acute myocardial infarction and mildly impaired left ventricular function.

Dobutamine stress echocardiography (DSE) accurately detects viable myocardium and residual ischemia in patients with acute myocardial infarction (AMI). The prognostic interaction of viability and ischemia has not been completely clarified in these patients. This study assesses the long-term effect of viability, ischemia, or their combination on survival in patients with AMI and mildly impaired left ventricular (LV) function. Four hundred eleven patients (age 57 +/- 9 years) underwent predischarge DSE (up to 40 microg/kg/min plus atropine if needed) after uncomplicated AMI and were prospectively followed for 23 months (range 1 to 78). According to DSE findings, patients were divided into 4 groups: viability only, ischemia only, combination of viability and ischemia, and scar. Adverse outcome occurred in 64 patients: 34 patients had hard events (9 cardiac deaths, 25 nonfatal AMI) and 30 patients had unstable angina requiring hospitalization. The combination of viability and ischemia, diabetes mellitus, and non-Q-wave AMI were significant predictors of all events at univariate and multivariate analysis. The same variables were also univariate predictors of hard events, but multivariate analysis indicated only the combination of viability and ischemia and diabetes as independent predictors. The event-free survival of patients with combined viability and ischemia was significantly lower (hazard ratio 3 [95% confidence interval 1.8 to 11]) compared with patients with ischemia only. Thus, viability and ischemia show a significant adverse prognostic interaction in patients with AMI and preserved LV function.

Non-invasive diagnostic and prognostic assessment of single-vessel coronary artery disease: focus on stress echocardiography.

AIMS: Revascularization procedures are increasingly applied in patients with single-vessel coronary artery disease in spite of the fact that a prognostic benefit has been proved only for soft end-points. This review summarizes the results of stress echocardiography in the diagnostic and prognostic assessment of these patients. METHODS AND RESULTS: The diagnostic and prognostic assessment of patients with single-vessel disease using stress (exercise, dobutamine, adenosine and dipyridamole) echocardiography are focused upon in the light of pathophysiological considerations and the results of clinical studies. Factors affecting test accuracy are individually addressed and comparisons made with different stress testing modalities, including exercise electrocardiography and nuclear techniques. Finally, therapeutic options are discussed and the superior accuracy of the physiological assessment of coronary stenosis as compared to the simple anatomic evaluation emphasized. CONCLUSIONS: Patients with single-vessel disease represent an anatomically heterogeneous group. Although the suboptimal performance of any technique in their evaluation has to be acknowledged, stress echocardiography can effectively contribute to selection of the management strategy.