Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic heart disease is an important and common contributor to the development of heart failure. Theoretically, all patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with ischemic heart disease may also theoretically benefit from the relief of ischemia, the prevention of coronary occlusion, and revascularization. However, there is little evidence to show that the presence or absence of coronary disease modifies the benefits of effective treatments such as angiotensin-converting enzyme inhibitors and beta-blockers. Moreover, there is no evidence that treatment directed specifically at myocardial ischemia or coronary disease alters outcome in patients with heart failure. Treatments aimed at relieving painless myocardial ischemia have not been shown to alter prognosis. Lipid-lowering therapy is theoretically attractive for patients with heart failure and coronary disease; however, theoretical concerns also exist about the safety of such agents, and patients with heart failure have been excluded from large outcome studies very effectively. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion seem ineffective or harmful in patients with heart failure, although warfarin may be safe and possibly effective. There is no evidence yet that revascularization improves prognosis in patients with heart failure, even in patients who are shown to have extensive myocardial hibernation. On current evidence, revascularization should be reserved for the relief of angina. Large-scale, randomized controlled trials are currently underway that are investigating the role of specific treatments targeted at coronary syndromes. The Carvedilol Hibernation Reversible Ischemia Trial: Marker of Success study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The Warfarin and Antiplatelet Therapy in Chronic Heart Failure study is comparing the efficacy of aspirin, clopidogrel, and warfarin. The Heart Revascularization Trial-United Kingdom study is assessing the effect of revascularization on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are assessing the safety and efficacy of statin therapy in patients with heart failure. Only once the outcomes to these and other planned trials are known can the medical community know how best to treat their patients.
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PMID:What is the optimal medical management of ischemic heart failure? 1125 Nov 29

Previous studies have shown that ischemia and reperfusion are potent stimuli for eliciting cardiomyocyte apoptosis, and that polymorphonuclear leukocytes (PMNs) are involved in the development of myocardial injury induced by ischemia and reperfusion. The present study examined whether PMN could directly induce cardiomyocyte apoptosis and, if so, it possible signal transduction pathways. In addition, we also investigated the effects of carvedilol, a potent antioxidant, on PMN-induced apoptosis. Cultured primary neonatal rat cardiomyocytes were exposed to PAF-activated PMNs at concentrations of 10(5), 3 x 10(5) and 10(6) cells/well for 48 h. Multiple detecting techniques, including electron microscopy, DNA gel electrophoresis. TUNEL assay and flow cytometry were used to identify myocyte apoptosis. All of these techniques demonstrated that activated PMNs directly induced cardiomyocyte apoptosis in a concentration-dependent manner, while unactivated PMNs showed no such effect. Activated PMN-induced apoptosis was partially inhibited by SB203580, a specific inhibitor of the p38-MAPK signaling system. Carvedilol (at a dose range of 1-10 mumol/l) significantly prevented activated PMN-induced cardiomyocyte apoptosis. These results suggest that PMNs, when activated, directly induce cardiomyocyte apoptosis and that the p38-MAPK signaling pathway might be involved in this process. Carvedilol may prevent PMN-induced apoptosis possibly because of its antioxidant properties.
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PMID:Activated polymorphonuclear leukocytes induce cardiomyocyte apoptosis and the protective effects of carvedilol. 1242 28

The Carvedilol Acute Myocardial Infarction Study (CAMIS) investigates cardiac remodeling in patients (n = 250) randomized to carvedilol vs atenolol and treated for 12 months after acute myocardial infarction. In a sub-study, we compared sympathetic, hemorrheological and vascular effects in small but particularly well-matched groups of participants who had been on reasonably equipotent but unchanged doses of carvedilol (n = 10) or atenolol (n = 10) for at least 4 weeks. Blood pressures (p < 0.05), plasma adrenaline (p = 0.034), plasma vasopressin (p = 0.022) and whole blood viscosity at shear rate 0.5 cp (p = 0.050), 1.1 cp (p = 0.023), 5.8 cp (p = 0.049) and 201 cp (p = 0.060) taken in the laboratory at baseline before 2 h of using the hyperinsulinemic, isoglycemic glucose clamp were lower on carvedilol. Plasma noradrenaline was lower on carvedilol at baseline and throughout the clamp (p < 0.0005). Forearm vascular resistance as measured by plethysmography during the clamp tended to be lower on carvedilol (p = 0.074). No significant difference was found between the groups in glucose disposal rate measured by clamp, maximal forearm blood flow and minimal forearm vascular resistance after 10 min of ischemia, or in ambulatory blood pressure and heart rate taken a few days later. Thus, potential benefits of carvedilol vs atenolol were seen in these post-infarction patients in a laboratory setting. These findings suggest that the inhibitory effects on the sympathetic nervous system and related blood viscosity are stronger with carvedilol than with atenolol.
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PMID:Lower plasma noradrenaline and blood viscosity on carvedilol vs atenolol in men with recent myocardial infarction. 1252 82

Carvedilol is a multiple-action drug with alpha(1)- and beta-adrenergic receptor antagonistic, calcium channel blocker and antioxidant activities especially useful in the treatment of hypertension. The antioxidant activity of the drug depends on the carbazole moiety, which is unique to carvedilol and is also present in some of the metabolites lacking either the alpha(1)- or beta-adrenergic receptor blocking activity. These antioxidant properties account for the exceptional ability of carvedilol to reduce cardiac necrosis in animal models of myocardial infarction, as well as its neuroprotective activities in in vivo and in vitro models of brain ischemia. A further property of carvedilol is its ability to inhibit vascular smooth muscle cell migration and proliferation, and neointima formation, after vascular injuries. The identification of all these activities of carvedilol indicates that it is a singular multiple-action antihypertensive agent with potential for cardiovascular organ protection beyond the normalization of high blood pressure.
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PMID:Carvedilol: an effective antihypertensive drug with antiischemic/antioxidant cardioprotective properties. 1474 60

There is increasing evidence to suggest that toxic oxygen radicals play a role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of carvedilol (CVD), an antihypertensive drug in I/R-induced renal failure in rats. The protective effect of CVD against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Sprague-Dawley rats using histopathological and biochemical parameters. In one set of experiments, animals were unilaterally nephrectomized, and subjected to 45 min of left renal pedicle occlusion and in another set both the renal pedicles were occluded for 45 min followed by 24 h of reperfusion. Carvedilol (2 mg/kg, i.p.) was administered twice, 30 min prior to ischemia and 12 h after the reperfusion period. At the end of the reperfusion period, rats were killed. Thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities were determined in renal tissue. Serum creatinine and blood urea nitrogen (BUN) concentrations were measured for the evaluation of renal function. Ischemic control animals demonstrated severe deterioration of renal function, renal morphology and a significant renal oxidative stress. Pretreatment of animals with CVD markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS levels and restored the depleted renal antioxidant enzymes. The findings imply that ROS play a causal role in I/R-induced renal injury and CVD exerts renoprotective effects probably by the radical scavenging and antioxidant activities.
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PMID:Carvedilol attenuates ischemia-reperfusion-induced oxidative renal injury in rats. 1554 33

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.
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PMID:Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress. 1569 97

It is well established now that beta-blockers are an important treatment of heart failure due to left ventricular systolic dysfunction. It has been shown that this drugs counteract the negative effects of sympathetic stimulation on the myocardium (myocardial hypertrophy, fibrosis and ischemia arythmogenic effect, increase of cardiac loading, apoptosis). Many big trials as CIBIS-II, MERIT-HF and CAPRICORN show that Bisoprolol, Metropolol and Carvedilol decrease the hospitalization rate due to heart failure, improve the functional status and increase the survival rate of patients in class II, Ill and IV. However, beta-blockers are not always safe and there use must be guided by some rules: respect of contra-indications (asthma, severe bradycardia, second or third atrio-ventricular block, arterial hypotension), initiation after 2 or 4 weeks of clinical stability, low initial doses with an increase every 2 or 4 weeks.
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PMID:[Beta blockers in the treatment of heart failure due to left ventricular systolic dysfunction]. 1577 41

Carvedilol is a beta- and alpha-adrenergic-blocking drug with clinically important antiarrhythmic properties. It possesses anti-ischemic and antioxidant activity and inhibits a number of cationic channels in the cardiomyocyte, including the HERG-associated potassium channel, the L-type calcium channel, and the rapid-depolarizing sodium channel. The electrophysiologic properties of carvedilol include moderate prolongation of action potential duration and effective refractory period; slowing of atrioventricular conduction; and reducing the dispersion of refractoriness. Experimentally, carvedilol reduces complex and repetitive ventricular ectopy induced by ischemia and reperfusion. In patients, carvedilol is effective in controlling the ventricular rate response in atrial fibrillation (AF), with and without digitalis, and is useful in maintaining sinus rhythm after cardioversion, with and without amiodarone. In patients with AF and heart failure (HF), carvedilol reduces mortality risk and improves left ventricular (LV) function. Large-scale clinical trials have demonstrated that combined carvedilol and angiotensin-converting enzyme inhibitor therapy significantly reduces sudden cardiac death, mortality, and ventricular arrhythmia in patients with LV dysfunction (LVD) due to chronic HF or following myocardial infarction (MI). Despite intensive neurohormonal blockade, mortality rates remain relatively high in patients with post-MI and nonischemic LVD. Recent trials of implantable cardioverter-defibrillators added to pharmacologic therapy, especially beta blockers, have shown a further reduction in arrhythmic deaths in these patients.
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PMID:Carvedilol's antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction. 1586 48

Carvedilol a beta-adrenoreceptor antagonist with potent antioxidant properties raises high expectations in therapy of ischemia. In this study the effect of carvedilol on neuronal survival after transient forebrain ischemia in gerbils was investigated. The role of poly(ADP-ribose) polymerase (PARP-1) in this process was evaluated. Our data indicated that carvedilol administered subcutaneously in a dose of 7 or 70 mg/kg b.w. directly after 5 min of transient forebrain ischemia protects significant population of neurons in hippocampal area CA1, but has no effect after induction of prolonged 10 min ischemia. Carvedilol significantly decreased PARP activity in hippocampus that was markedly increased after both 15 min and 4 days of reperfusion following 5 min of ischemia. Moreover, carvedilol prevented NAD+ depletion after ischemic-reperfusion insult. These results indicated that carvedilol protects neurons against death and suggested that suppression of PARP activity during reperfusion could be involved in this process.
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PMID:Effect of carvedilol on neuronal survival and poly(ADP-ribose) polymerase activity in hippocampus after transient forebrain ischemia. 1596 Feb 97

There have been few reports describing the use of carvedilol in children or patients with congenital heart disease. Therefore, its optimal regimen, efficacy, and safety in these patients have not been adequately investigated. Subjects were 27 patients with two functioning ventricles, for whom carvedilol was initiated (from December 2001 to December 2005) to treat heart failure. All patients had failed to respond to conventional cardiac medication. They consisted of 12 males and 15 females, aged 23 days to 47 years (median age: 2 years). Heart failure due to ischemia (myocardial infarction, intraoperative ischemic event) or due to myocardial disease (cardiomyopathy, myocarditis), and heart failure with atrial or ventricular tachyarrhythmia represented 70% of all cases. Carvedilol was initiated at a dose of 0.02-0.05 mg/kg/day, which was increased by 0.05-0.1 mg/kg/day after 2 days, 0.1 mg/kg/day after 5 days, and 0.05-0.1 mg/kg/day every month thereafter with a target dose of 0.8 mg/kg/day. This study retrospectively assessed the efficacy and adverse reactions based on changes of symptoms, cardiothoracic ratio (CTR), left ventricular ejection fraction (LVEF), and human atrial natriuretic peptide (hANP)/b-type natriuretic peptide (BNP) blood levels. The mean follow-up period was 10.2 months (range: 1-46 months). Twenty-six (96.3%) patients showed improvement in symptoms and were discharged from the hospital. However, the remaining one patient failed to respond and died. Significant cardiovascular adverse reaction was seen in none of the patients. The mean CTR decreased from 61.8% +/- 5.3% before treatment to 57.6% +/- 7.4% after treatment (P < 0.05, n = 25), and the mean LVEF improved from 41.4% +/- 23.1% to 61.1% +/- 10.1% (P < 0.05, n = 10), respectively. Mean hANP and BNP levels showed a decrease from 239.1 pg/ml to 118.3 pg/ml and a significant decrease from 437.9 pg/ml to 120.5 pg/ml, respectively (P < 0.05, n = 10). Improvements in these data were also demonstrated when analyzed individually among the pediatric group (aged younger than 18) and the congenital heart disease group. Initiation of carvedilol at a lower dose with more gradual dose escalation, compared with previously reported regimens, might have efficacy with low incidence of adverse effects in pediatric patients and patients with congenital heart disease. Carvedilol may be effective in treating heart failure in children due to ischemia, myocardial disease, and complicated by tachyarrhythmia.
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PMID:Efficacy and safety of carvedilol for heart failure in children and patients with congenital heart disease. 1946 19


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