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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent insights into the pathogenesis of vascular disease have opened up a new frontier that has implications for future therapies. The vasculature has been redefined as a vital organ that can regulate its own tone and structure via numerous cellular mechanisms. The endothelium plays the role of gatekeeper in this process, sensing and responding to stimuli and activating various vasoactive systems that function as mediators. Locally generated vasoactive substances such as angiotensin II and nitric oxide appear to be important determinants of vessel function and structure. Vasoactive substances generated within the endothelium influence cell proliferation and cell death in a complex interplay that, when disturbed, can result in structural alteration known as vascular remodeling. Normal vascular homeostasis is maintained by a balance between vasoconstrictors such as angiotensin II and vasodilators such as nitric oxide. Endothelial dysfunction involves an imbalance between vasoactive substances such that perturbations in the regulation of tone, hemostasis, and vessel structure result in the development of cardiovascular diseases, such as hypertension, atherosclerosis, and heart failure.
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PMID:Endothelial function as a determinant of vascular function and structure: a new therapeutic target. 912 14

In recent years, a prodigious amount of information has been gathered regarding the relationship between vascular biology and the mechanisms underlying cardiovascular disease. Activation of elements of the reninangiotensin system (RAS) appear to play an important role in the development and progression of conditions such as hypertension, coronary artery disease, and heart failure. Indeed, converging lines of evidence indicate that angiotensin-converting enzyme (ACE) regulates a delicate balance among a multitude of factors responsible for vascular tone, cellular growth promotion and inhibition, and pro- and anti-inflammatory effects. Because angiotensin II inhibits fibronectin, stimulates expression of plasminogen activator inhibitors, and degrades bradykinin, thereby impairing production of nitric oxide, ACE and the RAS are also involved in thrombosis and fibrinolysis. The favorable effects of ACE inhibition on endothelial function and, potentially, on cardiovascular morbidity and mortality are believed to result not only from angiotensin II suppression but also its consequent bradykinin preservation and nitric oxide production.
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PMID:The integrated effects of angiotensin II. 912 15

The endothelium produces several vasodilating factors such as prostacyclin or nitric oxide and also vasoconstricting agents such as endothelin. These factors play an important role in the regulation of vascular tone and tissue perfusion. Several recent studies have evaluated the role of endothelin and NO in the pathophysiology of congestive heart failure. This paper reviews the data suggesting that endothelin and NO contribute to the neuro-hormonal compensatory mechanisms in patients with heart failure and that specific blockade of endothelin receptors could be an effective new approach for the treatment of patients with severe congestive heart failure.
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PMID:[Endothelial factors and cardiac insufficiency]. 913 41

Recent evidence suggests that newer vasoselective dihydropyridine calcium antagonists are not cardiodepressant and may be useful in the treatment of heart failure. No data are available on the efficacy of clentiazem, a vasoselective benzothiazepine-like calcium antagonist, in this pathological condition. Therefore, our objective was to assess coronary and cardiac sensitivity to clentiazem in an experimental model of chronic heart failure (cardiomyopathic hamster, UM-X7.1, > 200 day old). Left ventricular developed pressure (LVP) and coronary flow changes were assessed in isolated, perfused failing hearts and in normal Syrian hamster hearts. Clentiazem dose-response curves for both coronary dilation and negative inotropic effects were determined under control conditions and in the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (L-NAME, 30 microM), and the cyclooxygenase inhibitor, indomethacin (10 microM). Baseline hemodynamics indicate a significant reduction in both LVP and coronary perfusion in failing hearts. Cardiac sensitivity to the negative inotropic effects of clentiazem were similar in normal and failing hearts (IC50 = 677 nM and 734 nM, respectively). However, the clentiazem-induced increase in coronary flow was significantly attenuated in failing hearts (EC50 = 56 +/- 9 nM vs. 15 +/- 3 nM in normal hearts, p < 0.01). To better characterize the reduced coronary sensitivity to clentiazem in the presence of heart failure, the contributions of the NO synthase and the cyclooxygenase pathways were evaluated. Although coronary sensitivity to clentiazem was significantly reduced in the presence of L-NAME, this attenuation was of the same magnitude in normal and failing hearts, suggesting that coronary "desensitization" to clentiazem in failing hearts does not involve the NO synthase pathway. Experiments carried in the presence of indomethacin indicate that the reduced coronary sensitivity to clentiazem observed in failing hearts does not involve the cyclooxygenase pathway. In conclusion, reduced coronary sensitivity to the vasoselective calcium antagonist clentiazem was observed in the failing hamster heart, while no exacerbation of clentiazem's cardiodepressant actions was present. Although the mechanisms involved in the vascular desensitization to clentiazem are still unknown, our findings may provide an additional explanation for the variable efficacy of calcium antagonists in the treatment of heart failure.
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PMID:Coronary and cardiac sensitivity to the vasoselective benzothiazepine-like calcium antagonist, clentiazem, in experimental heart failure. 914 Jun 81

Myocarditis is thought to be commonly caused by various viruses, and accumulating evidence links viral myocarditis with the eventual development of dilated cardiomyopathy. Recently, the importance of hepatitis C virus infection was noted in patients with dilated and hypertrophic cardiomyopathy. Cytokines are being increasingly recognized as an important factor in the pathogenesis and pathophysiology of myocarditis and cardiomyopathy. Elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. A number of reports have shown that cytokines generated by activated immune cells cause an increase in nitric oxide (NO) via induction of NO synthase. Increased generation of NO may induce negative inotropism and myocardial damage. This review discusses the etiology and pathogenesis of myocarditis and cardiomyopathy from this point of view.
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PMID:Molecular and immune mechanisms in the pathogenesis of cardiomyopathy--role of viruses, cytokines, and nitric oxide. 915 79

The pathogenesis of viral myocarditis has not been clarified yet especially in the subacute and chronic stages. Recent reports have shown that myocarditis may be caused by autoimmune reactions. Autoantigens and autoantibodies have recently been reported in myocarditis and cardiomyopathy, and most of them may be induced by the cross-reaction between virus and cardiac tissue, molecular mimicry, or by the destruction of immune tolerance. However it is not clear how autoimmune reactions affect viral myocarditis. We have reported that cytokines are increased in the blood of patients with myocarditis and cardiomyopathy. Many kinds of cytokines modulate viral myocarditis in different ways in murine models. Nitric oxide is also recognized as an important factor in viral myocarditis. We have reported that drugs for heart failure modulate cytokine production. Classifying drugs from this point of view may be helpful for developing new therapeutic strategy for patients with myocarditis and cardiomyopathy.
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PMID:[Viral myocarditis and autoimmunity]. 920 Sep 39

The predominant venodilator properties of the nitrates and their augmentation of collateral coronary blood flow to the ischemic myocardium endows them with some ideal characteristics for treating myocardial ischemic syndromes. Additional efficacy stems from the ability of the nitrates to replenish the deficient endothelium-derived relaxing factor (EDRF), nitric oxide (NO), in patients with coronary heart disease and also to inhibit platelet aggregation. In stable angina pectoris, the antianginal and antiischemic effects of oral nitrates are well established. Continuous administration of nitrates may lead to tolerance of their clinical efficacy. Recent studies, however, have demonstrated that when used in recommended doses, tolerance can be avoided during long-term treatment with oral nitrates without provocation of anginal attacks during periods of low nitrate levels at night and early hours of the morning. Thus, prolonged treatment with an asymmetric twice-daily regimen of immediate-release isosorbide-5-mononitrate in patients with stable angina pectoris does not give rise to clinical tolerance, prolongs exercise duration, and delays the onset of myocardial ischemia. In unstable angina pectoris, nitrates rapidly relieve chest pain and ameliorate the electrocardiographic signs of myocardial ischemia. In patients with acute myocardial infarction, early treatment with nitrates prevents left ventricular dilatation, improves pumping function, and reduces the risk of ventricular arrhythmias. In patients with chronic heart failure, oral nitrates improve exercise tolerance and, when given in combination with the systemic arterial dilator hydralazine, extend survival. Meta-analysis of published studies has demonstrated that both intravenous and oral nitrates reduced infarct size and morbidity and mortality in patients with acute myocardial infarction. In the ISIS 4 post-infarction study, isosorbide-5-mononitrate 60 mg once daily was not superior to placebo in reducing mortality risk. However, in the GISSI 3 study, the combination of nitrates with an angiotensin-converting enzyme (ACE) inhibitor reduced mortality risks by 17% in patients with acute myocardial infarction. In both the ISIS 4 and GISSI 3 studies, 62% and 57% of the patients in the placebo and control groups, respectively, were treated with nitrates for control of rest angina, myocardial ischemia, and or left ventricular failure symptoms, and this widespread use of open-label nitrates in the control groups may have diluted the true beneficial effects of nitrates in both studies. Taken together, these many studies with oral nitrate treatment in coronary heart disease and heart failure clearly emphasize that these drugs are safe and play more than a symptomatic role in the management of patients with acute and chronic ischemic syndromes due to coronary artery disease.
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PMID:Oral nitrates: more than symptomatic therapy in coronary artery disease? 921 Oct 13

To determine whether L-arginine, a precursor of nitric oxide, can improve exercise-induced vasodilation of the forearm in patients with heart failure, we measured forearm blood flow in 9 patients with heart failure and in 7 age-matched control subjects before and after intra-arterial infusion of L-arginine. Resting forearm blood flow was significantly lower in patients with heart failure than in control subjects (2.34 +/- 0.85 (SD) vs 4.76 +/- 0.77 ml/min per 100 ml, p < 0.001). Endothelium-dependent vasodilation induced by acetylcholine was attenuated in patients with heart failure (p < 0.05). Exercise-induced vasodilation after handgrip exercise was significantly lower in patients with heart failure (p < 0.05). Intra-arterial infusion of L-arginine did not change basal forearm blood flow but significantly augmented acetylcholine-induced vasodilation in both patients with heart failure and control subjects (p < 0.05). Although L-arginine did not affect maximum forearm blood flow after handgrip exercise in control subjects (before, 26.2 +/- 13.5; after, 25.7 +/- 14.3; p = NS), it was increased in patients with heart failure (from 15.2 +/- 4.9 to 24.7 +/- 14.6, p < 0.01). The finding that L-arginine increased both acetylcholine- and exercise-induced vasodilation in patients with heart failure suggests that endothelial dysfunction might play an important role in impaired exercise-induced vasodilation in patients with heart failure.
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PMID:L-arginine increases exercise-induced vasodilation of the forearm in patients with heart failure. 922 92

It is unknown whether basal release of endothelium-derived nitric oxide in the coronary artery is altered in heart failure in humans. The aim of the present study was to evaluate the effect of inhibition of nitric oxide synthesis on basal tone of the conduit and resistance coronary arteries in awake patients. Coronary blood flow velocity (Doppler guide wire) and coronary arterial diameter (quantitative coronary angiography) were measured in 14 patients with heart failure caused by nonischemic left ventricular dysfunction (7 idiopathic dilated cardiomyopathy and 7 valvular insufficiency) and 7 patients with normal ventricular function (controls). Intracoronary N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, at graded doses decreased coronary blood flow in both groups. However, the magnitude of flow reduction was smaller in patients with heart failure than in control patients (P<.0001). The magnitude of coronary blood flow reduction in response to L-NMMA inversely correlated to indexes of left ventricular contractile function (P<.01) but was not affected by the cause of heart failure. Constriction of the large epicardial coronary artery with L-NMMA also tended to be attenuated in patients with heart failure. In summary, vasoconstricting response to L-NMMA was blunted in the coronary resistance artery in heart failure in vivo. These findings suggest that basal release of nitric oxide in the coronary circulation is decreased in patients with heart failure.
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PMID:Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure. 923 20

The pathogenesis of heart failure is determined by the ventricular and vascular responses to myocellular injury. Experimental and clinical studies suggest that the vascular endothelium may play an important role in modulating progression of ventricular and vascular remodeling in heart failure. Endothelial cell dysfunction has been described in the coronary and skeletal muscle circulations of patients with heart failure and appears to be characterized by decreased endothelial synthesis of nitric oxide and increased production of endothelin-1. The pathogenesis of endothelial dysfunction in heart failure is unknown, but may be related to increased oxidative stress, abnormal regional flow conditions, and cytokine and neurohormonal activation. The specific role of endothelial dysfunction in the pathogenesis of heart failure remains to be determined. If endothelial dysfunction does contribute to progression of disease in early heart failure, specific therapies to enhance endothelial dysfunction may improve long-term morbidity and mortality.
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PMID:Mechanisms and implications of endothelial dysfunction in congestive heart failure. 924 83


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