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

Nitrate derivatives are venous vasodilators which are effective in reducing the symptoms of pulmonary congestion. The beneficial action on exercise capacity was recently demonstrated in the Veterans II Study in association with Hydralazine and has also been suggested by other trials. The reduction in mortality from cardiac failure was demonstrated in the Veterans I Study in association with Hydralazine compared to conventional digitalo-diuretic therapy but seems less important than that obtained by angiotensin converting enzyme inhibitors. The phenomenon of tolerance seems to be related to the use of high doses in continuous therapy and may be countered by discontinuous use of the drug during the 24 hour period. Tolerance seems to be related to neuro-hormonal factors and perhaps to depletion of SH groups. Simultaneous use of nitrates and ACE inhibitors seems to be an interesting therapeutic concept.
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PMID:[Nitrate derivatives and cardiac insufficiency]. 153 Apr 25

Nitrates are drugs of first choice in patients with acute heart failure. Acute pulmonary edema can be successfully treated with single or repeated doses of sublingual nitroglycerin. In cases of prolonged acute heart failure, e.g. in the setting of acute myocardial infarction, nitroglycerin or isosorbide dinitrate can be given by the intravenous route for up to 24 h. Patients with acute myocardial infarction usually benefit from nitrate therapy if filling pressures are high and/or left ventricular function is compromised. Nitrate therapy can be considered safe if arterial blood pressure is maintained above 95 mm Hg. With these precautions nitrates can reduce infarct size and the incidence of complications as well as improve long-term prognosis. In the chronic treatment concern has risen with regard to possible nitrate tolerance. Thus, therapy schedules allowing for nitrate-poor phases are generally recommended. Therapy schedules with constant-rate delivery of drugs achieved with patches or intravenous administration of nitrates should be used with caution.
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PMID:Nitrate therapy in heart failure. 176 Aug 30

The geometry of both the infarcted and non-infarcted zone of the left ventricle changes after myocardial infarction. Two mechanisms are involved: expansion of the infarcted zone and secondary dilatation of the non-infarcted zone. The necrosed area undergoes an inflammatory reaction followed by fibrosis which end up as a sca within a period of a few days to a few weeks. During this period if fibrous scarring the infarcted, thinned myocardium undergoes progressive expansion which starts in the first hours of the myocardial infarction. The loss of left ventricular systolic function related to the infarct and volumic overload created by expansion of the infarct influence the secondary development of dilatation of the non-infarcted zones. This dilatation results in restoration of left ventricular stroke volume but at the price of increased wall stress, which itself induces compensatory wall hypertrophy. These phenomena are more pronounced when the initial infarction is extensive and if they are sustained, they result in definitive myocardial failure. Several factors influence remodeling: the size of the infarct, arterial patency, wall stress and the quality of the scarring process itself. Therapeutic interventions of each of these factors can influence the remodeling. Limitation of infarct size by thrombolytic therapy, arterial revascularisation, even when performed late, seem capable of limiting expansion of the necrosed zone. Pharmacodynamic intervention of left ventricular afterload also affects ventricular remodeling. Nitrate derivatives, vasodilator therapy in general and converting enzyme inhibitors have been shown to be effective.
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PMID:[Physiopathology of left ventricular remodeling after myocardial infarction]. 183 20

Nitro derivates are effective agents for the treatment of myocardial ischemia. The effectiveness of these compounds in anginal disease is due to their ability to induce dilatation of veins which results in decreased left and right ventricular and diastolic pressure. Furthermore nitro derivates also bring about coronary vasodilatation which is present also in conditions of stenosis of epicardial arteries. In these conditions either coronary flow increases or its redistribution is more favorable. As the vasodilatory effect of nitro derivates does not involve sound arterioles, no "theft" of blood occurs. The dilatation of veins induced by nitrates explains also their effectiveness in patients suffering from heart failure with high left ventricular pressure. Mononitrates seem more effective than dinitrates since variability problems due to hepatic metabolism disappear. Nitrate plasters do not appear favourable since they produce constant blood levels and therefore could favour the development of tolerance.
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PMID:[Current status of pharmacology and therapeutic use of nitro derivatives]. 215 28

Despite the increasing insight in the clinical importance of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF), there is limited information about the metabolism and elimination of this mediator in humans. We studied the degradation of NO in healthy subjects inhaling 25 ppm for 60 minutes and in patients with severe heart failure inhaling 20, 40, and 80 ppm in consecutive 10-minute periods. In other healthy subjects, the renal clearance of NO metabolite was measured. The metabolism ex vivo was evaluated by direct incubation of nitrite, the NO oxidation product, in blood from healthy humans. During inhalation of NO, the plasma levels of nitrate increased progressively, both in the healthy subjects (from 26 to 38 mumol/L, P < .001) and in the patients (from 72 to 90 mumol/L, P < .001). Methemoglobin (MetHb) also increased in the healthy subjects (from 7 to 13 mumol/L, P < .001) as well as in the patients (from 19 to 42 mumol/L, P < .01). No change in nitrosohemoglobin (HbNO) was detected, either in the healthy subjects or in the patients. In arterialized blood (O2 saturation, 94% to 99%), incubated nitrite was semiquantitatively converted to nitrate and MetHb. In venous blood (O2 saturation, 36% to 85%) moderate amounts of HbNO were also formed. Plasma and urinary clearance of nitrate in healthy subjects averaged 20 mL/min. We conclude that uptake into the red blood cells with subsequent conversion to nitrate and MetHb is a major metabolic pathway for endogenously formed NO. Nitrate may then enter the plasma to be eliminated via the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. 822 83

Nitrate tolerance is a clinical problem in patients with coronary artery disease and heart failure. Human internal mammary arteries and saphenous veins obtained intraoperatively were suspended in organ chambers, and isometric tension was measured. In the artery, nitroglycerin elicited a potent relaxation, which was significantly diminished after prolonged incubation with nitroglycerin (10(-6) M, 1 h). In contrast, no tolerance occurred in saphenous vein under the same conditions. However, incubation with 10(-5) M nitroglycerin also developed tolerance. Compared to nitroglycerin, the new cysteine-containing mononitrate SPM 5185 exhibited a lower sensitivity but comparable maximal relaxation in arteries and veins. In nitroglycerin-tolerant arteries and veins, SPM 5185 caused relaxations similar to those under control conditions. Our results show that in isolated blood vessels, vascular nitrate tolerance occurs more readily in the mammary artery than in the saphenous vein. SPM 5185 seems to be less prone to the development of tolerance, which may be advantageous during chronic nitrate therapy.
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PMID:Development of nitrate tolerance in human arteries and veins: comparison of nitroglycerin and SPM 5185. 858 81

Organic nitrates have frequently been used for the treatment of patients with congestive heart failure (CHF). Nitrate tolerance has been identified as a major limitation of this therapy preventing a continuous effect. In the past several years, an effort has been made to develop strategies to prevent nitrate tolerance. Recent animal experimentation has demonstrated the prevention of nitrate tolerance with a concomitant administration of hydralazine. A later study demonstrated similar results in a patient with chronic CHF. The use of oral hydralazine (75 mg qid) resulted in prevention of early development of nitrate tolerance and attenuation of nitrate mediated hemodynamic effects which occurred within the first several hours after initiation of nitroglycerin therapy in the control group not receiving hydralazine. Recent data obtained in in vitro studies have demonstrated enhancement of vascular superoxide production secondary to exposure to nitrates which may be an important mechanism leading to nitrate tolerance. These same studies demonstrated a strong antioxidant effect of hydralazine reducing superoxide formation and preventing nitrate tolerance. Both animal and human experiments have demonstrated prevention of nitrate tolerance with a concomitant use of hydralazine. In vitro studies suggest that hydralazine, by virtue of its antioxidant effect, prevents the nitrate-mediated formation of vascular superoxide, and thus prevents nitrate tolerance. These data provide an explanation for the benefit demonstrated in the V-HeFT studies with the combination of isosorbide dinitrate and hydralazine in the treatment of patients with chronic CHF, and provide a support for the use of this therapeutic regimen in the treatment of patients with chronic heart failure.
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PMID:Prevention of nitrate tolerance with concomitant administration of hydralazine. 863 19

Nitrates have been widely used for the treatment of patients with chronic congestive heart failure. Although the use of these drugs has not been evaluated by large-scale studies traditionally used for evaluation of new therapy, multiple studies over the years have demonstrated their favorable effects. Organic nitrates have been shown to have a beneficial effect on ischemia, hemodynamic profile, magnitude of mitral regurgitation, endothelial function, and cardiac remodeling. These drugs alone or in combination with hydralazine have improved exercise capacity, maximal oxygen consumption, cardiac function, and survival. The use of nitrates in patients with heart failure has been limited by reduced responsiveness (resistance) and early development of tolerance. Nitrate resistance is due to reduced vascular response and results in the need to use a larger dose of any nitrate preparation when used for the treatment of patients with heart failure compared to patients without heart failure. Recent information suggests that nitrate tolerance is caused by increased levels of superoxide at the vascular wall, which leads to reduced nitric oxide level and to increased sensitivity to vasoconstrictive mechanisms, such as endothelin and angiotensin II. Intermittent dosing of nitrates allowing a 12-hour nitrate-free interval is effective in preventing nitrate tolerance and is, therefore, recommended. Recent information suggests that augmentation of nitrate dose by the use of an escalating dose regimen and a concomitant use of hydralazine can prevent or overcome the effect of nitrate tolerance in patients with heart failure.
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PMID:Nitrates in the treatment of congestive heart failure. 863 26

We assessed the levels of exhaled nitric oxide (eNO) in patients with chronic heart failure (CHF) according to the functional impairment and the use of nitrate-containing agents. Forty patients (age 55+/-9 years) were classified according to the NYHA classes I-II (n=18, group 1) and classes III-IV (n=22, group 2), and to the use of nitrate-containing drugs (Nitrate+, Nitrate-). Twenty-two healthy age-related subjects served as controls (group 3). Respiratory function, symptom-limited incremental cycloergometry and resting eNO concentration at peak (FENOp) or plateau (FENOpl) of the single-breath exhalation curve were assessed in all subjects. FENOpl was significantly lower in patients than in controls (7.8+/-2.7 and 10.6+/-2.8 ppb, respectively, P<0.005) and lower in most severe CHF patients (7.1+/-2.6 and 8.8+/-2.7 ppb in group 2 and group 1, respectively, P<0.05). A significant correlation between peak V'O(2), Watts and FENOpl (r=0.42, P<0.013 and r=0.46, P=0.008, respectively) was found. Independent of NYHA class, Nitrate+ showed higher FENOp levels than Nitrate- patients (36.9+/-15.7 vs. 28. 1+/-15.1 ppb, P<0.05). Resting eNO was lower in the most compromised CHF patients and was significantly related to exercise capacity. Nitrate-containing agents might influence the levels of eNO in these patients.
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PMID:Endogenous nitric oxide in patients with chronic heart failure (CHF): relation to functional impairment and nitrate-containing therapies. 1081 49

Since the first publication of isosorbide mononitrate 30% immediate-release 70% sustained-release (IR-SR) formulation in 1985, a considerable body of literature concerning its clinical efficacy and safety has become available. Theoretically, the formulation has the advantage over conventional isosorbide mononitrate or dinitrate (ISMN/ISDN) that it has a simpler and more predictable pharmacokinetic profile. The objectives of this paper are to review published data so far and to see whether the theoretical advantages translate into better clinical effectiveness. 1. After oral administration, isosorbide mononitrate IR-SR has a rapid onset of action (30 minutes), and effects are evident for up to 17 hours. 2. The antianginal effects of once-daily isosorbide mononitrate IR-SR increased with increasing dosages, were generally larger than those of either placebo or equipotent doses of conventional ISMN/ISDN, and were somewhat larger than those of the beta blocker bupranolol. The effects were generally similar to those of sustained release nifedipine. 3. Patients showed significantly greater improvement in some quality-of-life indices with once-daily isosorbide mononitrate IR-SR than with twice or three times daily regimens of conventional ISMN/ISDN. This was particularly so with mobility, psychological distress, and life satisfaction indices. 4. Tolerance did not develop after 13 months of once daily isosorbide dinitrate IR-SR. No rebound increase in incidence of ischemic episodes was observed after discontinuation of treatment. 5. Long-term efficacy data both of isosorbide mononitrate IR-SR and of conventional ISMN/ISDN are limited so far. Large studies in patients with angina pectoris and patients with heart failure addressing long-term effects are ongoing, and some of the data will be completed within the next months. Isosorbide mononitrate IR-SR has a rapid onset of action and has been shown to be clinically efficient and, in addition, to be more so than conventional ISMN / ISDN. Nitrate tolerance with continued use of the formulation has not yet been reported. Long-term effects on morbidity and mortality are currently being assessed.
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PMID:Isosorbide mononitrate 30% immediate-release 70% sustained-release formulation: a review. DUMQOL (DUtch Mononitrate Quality of Life) Study Group. 1095 15


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