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Biomedical subjects

M Metra

Publications and source records attributed to M Metra.

At least 19 recordsLinked to original sources
PubMed2003

[Adhesive molecules as immunologic markers of activity of multiple sclerosis].

The correlations between concentrations of the adhesive circulating molecules cICAM-1 and cVCAM-1 in the peripheral blood of patients with relapses-remitting multiple sclerosis (RRMS) in different clinical phases and magnetic resonance imaging (MRI) activity are presented. The patients in clinically active phase with Gd-enhancing lesions had elevated blood levels of cICAM-1. However, 5 patients without Gd-enhancing lesions exhibited elevated cICAM-1 and cVCAM-1 levels in active phase comparing to those in remission stage that indicate a high level of sensibility of these immunologic parameters.

Adolescent↗
PubMed2001

Beta-blockade in heart failure: selective versus nonselective agents.

Controlled clinical trials performed in more than 13 000 patients have, to date, consistently shown the beneficial effects of long term beta-adrenoceptor antagonist (beta-blocker) therapy in patients with chronic heart failure. It is not clear whether this represents a class effect or whether it is specific only to some agents. Beneficial effects on the prognosis of patients with mild to moderate heart failure have been shown with metoprolol, bisoprolol, and carvedilol. These beta-blockers, however, differ in their pharmacologic characteristics. Metoprolol and bisoprolol are selective for beta(1)-adrenergic receptors and are devoid of ancillary properties. Carvedilol, at a dosage of 50 mg/day, blocks all beta(1)-, beta(2)-, and alpha(1)-adrenergic receptors, and it has associated antiproliferative and antioxidant activities. These differences cause a varied acute hemodynamic response, with a reduction in cardiac output and a tendency toward a rise in pulmonary wedge pressure with selective agents and no change in cardiac output and a slight decrease in pulmonary pressures with carvedilol. Accordingly, when the therapy is started, the most frequent adverse effects are worsening heart failure with metoprolol and bisoprolol, and hypotension and dizziness with carvedilol. It remains controversial whether these differences also influence the long term effects of therapy. Carvedilol may provide a more comprehensive blockade of the cardiac adrenergic drive than selective beta-blockers because it does not upregulate beta(1)-adrenergic receptors, blocks all adrenergic receptors and decreases cardiac norepinephrine release. These properties may lead to a larger increase in left ventricular function and a lack of improvement in maximal exercise capacity with carvedilol, compared with selective beta-blockers. It is, however, unclear whether these differences also influence patient outcome. The long term effects of different beta-blockers on prognosis are currently being compared in the Carvedilol or Metoprolol European Trial (COMET) in which more than 3000 patients with chronic heart failure have been randomized in a 1 : 1 ratio to receive metoprolol or carvedilol.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

[Role of inflammation mediators in the pathogenesis of heart failure].

A number of factors are involved in congestive heart failure pathogenesis. Among these, inflammatory mediators could have a crucial role. Patients with congestive heart failure show increased plasma levels of "proinflammatory cytokines", in particular tumor necrosis factor-alpha and interleukin-6. Clinical and experimental models have demonstrated that these cytokines induce left ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the possibility that increased plasma concentration of cytokines could not be just an epiphenomenon, but an effective pathogenetic mechanism of disease progression. Additional inflammatory proteins involved in the acute phase response could play a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long pentraxin, structurally related, although with different functions, to C-reactive protein, is produced by immune system cells, fibroblasts and particularly by cardiac endothelial cells and myocytes, as demonstrated in murine and human models. Its synthesis is rapidly induced after exposition to bacterial lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the acute local inflammatory response to myocardial injury (e.g. necrosis) and in heart failure pathogenetic mechanisms, but its exact role is not yet settled. Defining the specific part played by these molecules in the pathogenesis of heart failure could lead to new therapeutic approaches in the treatment of cardiac insufficiency.

Cytokines↗
PubMed2000

PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans.

BACKGROUND: Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS: Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Aged↗
PubMed2000

Differential effects of beta-blockers in patients with heart failure: A prospective, randomized, double-blind comparison of the long-term effects of metoprolol versus carvedilol.

BACKGROUND: Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. METHODS AND RESULTS: We randomized 150 patients with heart failure (left ventricular ejection fraction </=0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124+/-55 mg/d), patients treated with carvedilol (49+/-18 mg/d) showed larger increases in left ventricular ejection fraction at rest (+10.9+/-11.0 versus +7.2+/-7.7 U, P=0.038) and in left ventricular stroke volume and stroke work during exercise (both P<0. 05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P<0.05). In contrast, the metoprolol group showed greater increases in maximal exercise capacity than the carvedilol group (P=0.035), but the 2 drugs improved symptoms, submaximal exercise tolerance, and quality of life to a similar degree. After a mean of 23+/-11 months of follow-up, 21 patients in the metoprolol group and 17 patients in the carvedilol group died or underwent urgent transplantation. CONCLUSIONS: The present study demonstrates that during long-term therapy, carvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be effective in clinical trials. These differences were likely related to a greater antiadrenergic activity of carvedilol.

Adrenergic beta-Antagonists↗
PubMed2000

Selective or nonselective beta-adrenergic blockade in patients with congestive heart failure.

Controlled clinical trials, performed in more than 13,000 patients, have consistently shown the beneficial effects of long-term beta-blocker therapy in patients with chronic heart failure. However, it is not clear whether this is a class effect or if it is specific only for some agents. Beneficial effects on the prognosis of the patients with mild to moderate heart failure have been obtained with metoprolol, bisoprolol, and carvedilol. Metoprolol and bisoprolol are selective for beta(1)-receptors and without ancillary properties, carvedilol, at doses of 25 mg twice daily, blocks beta(1)-, beta(2)-, and a(1)-adrenergic receptors, and has associated antiproliferative and antioxidant activities. These differences are important for the acute hemodynamic effects, but it is still controversial whether they may also influence the long-term effects of therapy. Differently from selective b-blockers, carvedilol blocks all adrenergic receptors, does not upregulate beta1-receptors, decreases cardiac norepinephrine release, and has associated antioxidant effects. These differences may cause a larger increase in left ventricular function, which was significant in some, but not all of the direct comparisons of the two agents. The long-term effects of different beta-blockers on prognosis are currently compared in the Carvedilol or Metoprolol European Trial, in which more than 3000 patients with chronic heart failure have been 1:1 randomized to metoprolol or carvedilol and are going to be followed for more than 2 years.

Adrenergic beta-Antagonists↗
PubMed2000

A rationale for the use of beta-blockers as standard treatment for heart failure.

BACKGROUND: Cardiac sympathetic activation is one of the major and earlier changes observed in patients with heart failure. Its relation to the severity of the disease and its independent prognostic value show that it may directly contribute to the progression of heart failure. beta-Blockers are the most effective tool to counteract the untoward effects of sympathetic activation on the cardiovascular system. METHODS AND RESULTS: We reviewed the results of the placebo-controlled, double-blind studies about the effects of beta-blockers in patients with heart failure. These studies have involved almost 10,000 patients to date and have consistently shown that the long-term administration of beta-blockers is associated with a highly significant improvement in both left ventricular function and prognosis of the patients with heart failure. The evidence supporting the use of beta-blockers now equals or even surpasses that of angiotensin-converting enzyme inhibitors; therefore beta-blockers should be considered part of standard therapy. Issues that remain unclarified include the mechanisms through which beta-blockers may improve cardiac function and their tolerability and efficacy in specific groups of patients (such as those with asymptomatic left ventricular dysfunction, severe heart failure, the elderly, or those with left ventricular diastolic dysfunction). It is not currently clear whether the pharmacologic differences between individual beta-blockers are clinically relevant. If they are, the potential for even greater benefit with certain agents exists. It is hoped that these issues will be clarified by the results of ongoing multicenter trials.

Adrenergic beta-Antagonists↗
PubMed1999

Use of cardiopulmonary exercise testing with hemodynamic monitoring in the prognostic assessment of ambulatory patients with chronic heart failure.

OBJECTIVES: We studied whether direct assessment of the hemodynamic response to exercise could improve the prognostic evaluation of patients with heart failure (HF) and identify those in whom the main cause of the reduced functional capacity is related to extracardiac factors. BACKGROUND: Peak exercise oxygen consumption (VO2) is one of the main prognostic variables in patients with HF, but it is influenced also by many extracardiac factors. METHODS: Bicycle cardiopulmonary exercise testing with hemodynamic monitoring was performed, in addition to clinical evaluation and radionuclide ventriculography, in 219 consecutive patients with chronic HF (left ventricular ejection fraction, 22 +/- 7%; peak VO2, 14.2 +/- 4.4 ml/kg/min). RESULTS: During a follow-up of 19 +/- 25 months, 32 patients died and 6 underwent urgent transplantation with a 71% cumulative major event-free 2-year survival. Peak exercise stroke work index (SWI) was the most powerful prognostic variable selected by Cox multivariate analysis, followed by serum sodium and left ventricular ejection fraction, for one-year survival, and peak VO2 and serum sodium for two-year survival. Two-year survival was 54% in the patients with peak exercise SWI < or = 30 g x m/m2 versus 91% in those with a SWI >30 g x m/m2 (p < 0.0001). A significant percentage of patients (41%) had a normal cardiac output response to exercise with an excellent two-year survival (87% vs. 58% in the others) despite a relatively low peak VO2 (15.1 +/- 4.7 ml/kg/min). CONCLUSIONS: Direct assessment of exercise hemodynamics in patients with HF provides additive independent prognostic information, compared to traditional noninvasive data.

Adult↗
PubMed1998

Maximal and submaximal exercise testing in heart failure.

Although reduced exercise capacity is the main complaint of patients with congestive heart failure (CHF), the best method to measure it remains controversial. Peak VO2, obtained using maximal exercise testing, is the most accurate measure of maximal functional capacity. It is related to peak exercise cardiac output and is one of the most important independent variables for the prognostic assessment of patients with CHF. It has, however, a low sensitivity for measurement of changes induced by therapy and is poorly related to everyday physical activity, patient symptoms, and quality of life. The anerobic threshold may also be regarded as a parameter of maximal functional capacity. Its value is mainly indirect, because it shows that the patient is performing a maximal effort limited by the cardiovascular system. The VO2 kinetics at the start and at the end of exercise are probably more related to patient symptoms, but it is unresolved which protocols and parameters might best be used to study this aspect of exercise performance. Duration of a submaximal exercise at a constant work rate and the distance walked during a 6-min walking test are gaining wide popularity as parameters of submaximal performance. However, when these exams are carried out up to exhaustion in patients with severe functional limitation, they may involve attainment of the anerobic threshold and therefore their clinical meaning may be similar to the one of a maximal exercise test. Moreover, tests based on the assessment of submaximal exercise capacity have been useful for assessment of therapy in single-center trials but have been often inadequate in multicenter trials.

Anaerobic Threshold↗
PubMed1998

Effects of neurohormonal antagonism on symptoms and quality-of-life in heart failure.

Increased mortality and reduced functional capacity are the two main characteristics of chronic heart failure. Activation of the renin-angiotensin and sympathetic systems has a primary role in the progressive worsening of heart failure and increased mortality of patients. In addition, both systems may be important in the pathogenesis of exercise intolerance, although there is only a weak relationship between neurohormonal activation and exercise capacity. While neurohormonal antagonists, such as angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, consistently improve the prognosis of patients with heart failure, their effects on exercise tolerance have often been less significant. This problem has been emphasized by the introduction of beta-blockers for the therapy of heart failure. Beta blockade results in a significant improvement in left ventricular function during rest and exercise. However, the reduction in chronotropic response to exercise as well as the metabolic changes caused by these agents in skeletal muscle may result in an apparent lack of change in maximal functional capacity. This effect is particularly important with the new third generation non-selective beta-blockers. The pronounced anti-adrenergic activity of these compounds accounts for their greater negative chronotropic effect and relates to the lack of improvement in peak oxygen consumption (VO2). Submaximal exercise testing can be used to assess changes induced by these agents. However, even the six-minute walk test may act as an almost maximal test in patients with advanced heart failure: moreover, the measurement of submaximal exercise duration may be sensitive enough to detect changes in single-centre trials, but not in multicentre trials. To date, direct assessment of symptoms by both patient and physician is still the most sensitive tool to monitor changes in functional status with non-selective beta-blockers. Thus, an accurate method of measuring patients' symptoms, in addition to the clinical examination, is still necessary when neurohormonal antagonists are used in patients with chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed1998

[Etiopathogenesis of acute myocardial infarction: role of early leukocytosis].

It has recently been suggested that inflammation may play an important role in the pathogenesis of acute ischemic syndromes. It may therefore be important to relate their clinical features with plasma indexes of inflammation. We have studied leukocyte, platelet and fibrinogen blood levels in 57 consecutive patients with acute myocardial infarction admitted to our Intensive Care Unit within 90 min after the onset of chest pain and treated with primary coronary angioplasty. Patients were divided into two groups on the basis of blood leukocyte levels: Group A, 24 patients, 17 males, mean age 54.2 +/- 13.7 years, with high blood leukocytes and Group B, 33 patients, 28 males, mean age 60.9 +/- 10.3 years, with normal blood leukocytes. Group A patients also had higher serum fibrinogen (p = 0.05) and blood platelet levels (p < 0.05). The stenosis observed after guidewire advancement was significant (> 75%) in 33% of the patients with leukocytosis vs 94% of the others (p < 0.01). No difference between the two groups was observed in the success rate of coronary angioplasty and prevalence of stent placement (100 vs 97%, and 43 vs 42% of the patients of Group A and B, respectively). In contrast, a tendency to rethrombosis requiring Rheopro administration was observed in 62% Group A patients vs 21% Group B patients (p < 0.01). In conclusion, the finding of leukocytosis in the acute phase of myocardial infarction suggests that coronary occlusion is mainly caused by a coronary thrombus occurring at the site of a non significant stenosis. In contrast, when blood leukocytes are normal, the underlying coronary stenosis is more often critical and the thrombotic process is less important. The high blood leukocytes, platelet and fibrinogen levels of Group A patients are consistent with a significant role of inflammation in the pathogenesis of the thrombotic process while hemodynamic and local mechanical factors are probably more important in patients with normal blood leukocytes.

Adult↗
PubMed1997

[The effects of mid- and long-term administration (3-4 years) of carvedilol in patients with idiopathic dilated cardiomyopathy].

Carvedilol has been shown to determine a significant improvement in left ventricular function, symptoms, clinical course and prognosis of patients with chronic heart failure. However, these results were obtained in medium-term studies of < 1 year duration. We report the results obtained with long-term (3-4 years) carvedilol administration to 40 patients with idiopathic dilated cardiomyopathy who were initially recruited in a 4-month double-blind placebo-controlled trial. In the initial 4-month double-blind trial, 20 patients were randomized to placebo and 20 to carvedilol treatment. All patients, except one who was not on ACE-inhibitors, were on digoxin, furosemide and ACE-inhibitors. Carvedilol or placebo doses were progressively titrated, at weekly intervals, up to the maximal doses of 25 mg bid. After the initial 4-month double-blind phase, all patients were followed long term. Mean follow-up duration was 52 +/- 12 months (range 48-61). Among the 20 patients initially randomized to carvedilol administration, 4 died (3 for cardiac and 1 for extracardiac causes) and 2 underwent heart transplant. Among the 20 patients initially randomized to placebo, 5 died for cardiac causes, 3 underwent heart transplant and 4 were started on carvedilol because of progressive heart failure during the initial 4 months of the study. The remaining 8 patients, who were kept on digoxin, furosemide and ACE-inhibitors, were used as control group. Each patient underwent an assessment of clinical conditions (NYHA functional classification and Minnesota Living with Heart Failure questionnaire), equilibrium radionuclide ventriculography, and maximal cardiopulmonary bicycle exercise testing. Exams were performed before treatment, after 4 and 12 months, and at the end of the follow-up period. No significant difference between the carvedilol and control group was present at baseline. Compared with baseline, patients in the control group presented a significant increase in left ventricular end-diastolic volume after long-term follow-up (from 126 +/- 62 to 138 +/- 43 and 158 +/- 52 ml/m2 after 12 and 48 months, respectively). No significant difference, compared to baseline values, was noted. Patients on carvedilol presented a persistent improvement in left ventricular function. This was shown by the progressive increment in left ventricular ejection fraction from 22 +/- 6 to 34 +/- 11, 37 +/- 11 and 37 +/- 13%, after 4, 12 and 48 months, respectively (p < 0.001) with a concomitant reduction in left ventricular end-diastolic volume from 147 +/- 54 to 101 +/- 44 ml/m2 at the end of the follow-up (p < 0.05). NYHA functional class remained significantly improved, in comparison with baseline (2.6 +/- 0.5 to 1.9 +/- 0.3, 1.9 +/- 0.8 and 2.0 +/- 1.0 after 4, 12 and 48 months, respectively; p < 0.01). Maximal functional capacity, assessed as peak VO2 was not significantly changed after 4 months (from 15.2 +/- 3.6 to 16.4 +/- 4.0 ml/kg/min) and showed a tendency towards a further improvement after 12 months and at the end of the follow-up (17.3 +/- 5.6 and 17.2 +/- 5.3 ml/kg/min, respectively). These results show that the favorable effects of carvedilol administration on left ventricular function and clinical symptoms are maintained also after long-term treatment.

Adrenergic beta-Antagonists↗
PubMed1997

[Evolution in coronary stenting: use of ticlopidine with and without oral anticoagulants].

Implantation of intracoronary stents has been rapidly increasing in the last few years, especially after a reduction of restenosis has been shown. The main limitation in the use of coronary endoprosthesis is still represented by acute and subacute thrombosis. In order to limit this dangerous complication a very strong coagulant regimen, which has been improved since 1993-94, was initially recommended. We report our experience with patients who underwent a stent implantation comparing two therapeutic regimens with or without oral coagulants associated with antiplatelet agents. During 700 consecutive coronary angioplasties 128 Palamatz-Schatz and Wiktor stents have been implanted in 118 patents (16.9%). After stent implantation, 33 patients underwent a traditional anticoagulant therapy with heparin followed by oral anticoagulants for 3 months. They were also treated with ticlopidine 250 mg/die started 2 days before the procedure and then kept at least one month (group A). Eighty-five patients were treated only with antiplatelet therapy (ticlopidine 500 mg/die) started 2 days before implantation (group B). These two groups of patients were similar in age, sex, type and number of treated vessels and in diameter of the vessel with stent implantation. Subacute thrombosis rate was not significantly different between groups (3 vs 2.3%, NS). The predictive factors of thrombosis were acute myocardial infarction and implantation of multiple stents. No significant differences were found between thrombosis of the stents implanted in bail-out conditions compared to the elective ones. Ticlopidine started 2 days before stent implantation seems to be sufficient to limit thrombosis rate; moreover it allows a reduction of the hemorrhagic complications and hospitalization period.

Administration, Oral↗
PubMed1996

Role of exercise ventilation in the limitation of functional capacity in patients with congestive heart failure.

Patients with heart failure have, compared with normal subjects, an increased minute ventilation (VE) at matched workloads. This heightened ventilatory drive may contribute to their limitation of functional capacity through an increase in the work of breathing and further worsening in the lung ventilation-perfusion mismatch. To measure the ventilatory response to exercise, VE should not be assessed in absolute units but be related to one of its main determinants, e.g., carbon dioxide production (VCO2). Particularly, as VE is closely related to VCO2 during exercise, the ventilatory response to exercise has been assessed using the slope of the relation of VE versus VCO2. This slope is significantly increased in heart failure patients compared with normal subjects and is inversely related to other parameters of maximal exercise capacity, namely peak VO2. The mechanisms of exercise hyperpnea in heart failure patients are still unsettled. A first possibility is that it is a compensatory response to the abnormal exercise hemodynamics with secondary increase of the pulmonary dead space to tidal volume ratio. This mechanism should be aimed to maintain constancy of the arterial gas composition and acid-base balance. However, exercise-induced hypoxemia and/or hypercapnia do not generally develop in heart failure patients. This might imply that other mechanisms, such as an increased sensitivity of the arterial chemoreceptors and/or the activation of reflexes by the abnormal skeletal muscles, stimulate the ventilatory response in heart failure patients. Regardless of its mechanisms, exercise hyperpnea may be clinically relevant in the assessment of patients with chronic heart failure. In fact, it is inversely related with peak exercise capacity, and interventions known to improve peak functional capacity such as therapy with ACE inhibitors, physical training and heart transplantation, also tend to normalize exercise hyperpnea.

Exercise↗
PubMed1996

Pharmacological activity of the new calcium antagonist, lacidipine, on isolated preparations.

1. The calcium-channel blocking activity of lacidipine has been studied compared with that of nifedipine and verapamil on the isolated rabbit heart and aorta. 2. All the compounds induced a dose-dependent negative inotropic effect (10(-8)-10(-5) M); although lacidipine showed less, but longer lasting, activity. 3. Lacidipine showed a weak negative chronotropic effect and nifedipine was ineffective. Only verapamil strongly decreased the heart rate. 4. The three calcium antagonists abolished vasopressin-induced coronary spasm and inhibited partially metoxamine-induced coronary spasm. Only lacidipine reduced basal coronary pressure. 5. In the aortic strips, all the compounds antagonized KCl-induced contractions, and they exerted a partial effect on noradrenaline- and angiotensin II-induced contractions.

Animals↗