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

Tolerance develops during the prolonged use of organic nitrates in patients with chronic heart failure in a fashion similar to its development in patients with angina pectoris, the magnitude of tolerance development being directly proportional to the frequency of dosing. When nitroglycerin is given continuously or when isosorbide dinitrate is administered frequently throughout the day (e.g., every 4h), haemodynamic tolerance develops completely in most patients within 24-48h. Such tolerance can be avoided, however, when these drugs are given intermittently (e.g., every 8 or 12 h). Unfortunately, most clinical trials with isosorbide dinitrate have attempted to produce continuous haemodynamic effects by administering the drug at frequent intervals; this may explain why these trials have produced equivocal results. Two mechanisms have been proposed to explain the development of tolerance in patients with chronic heart failure. According to the first hypothesis, tolerance develops as a result of the depletion of intracellular sulfhydryl groups that are essential to the ability of nitroglycerin to activate guanylate cyclase--the key enzyme in the action of nitrates on blood vessels. According to the second hypothesis, tolerance develops as a result of the activation of endogenous neurohormonal systems; the resulting vasoconstriction limits the direct effects of the nitrovasodilators. A better understanding of both mechanisms may lead to interventions that will circumvent the development of tolerance and enhance the efficacy of long-term nitrate therapy.
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PMID:The clinical significance of nitrate tolerance in patients with chronic heart failure. 266 3

The plasma concentrations of 6-chloro-2-pyridylmethyl nitrate after sublingual administration were determined in six healthy male volunteers (venous plasma) and eleven patients (arterial plasma) with ischemic heart failure. The pharmacokinetics of the compound was investigated in volunteers. Plasma concentration-time data in each volunteer were found to fit a two-compartment open model with zero-order absorption. The pharmacokinetic parameters estimated from curve-fitting the plasma concentration-time data were as follow: Tmax 10 +/- 2.8 min, Cmax 8.16 +/- 2.48 ng/mL and CLP 6.16 +/- 1.79 L/min (means +/- S.D.). The arterial plasma concentrations (11.9 +/- 5.14 ng/mL) 7 min after sublingual administration were significantly higher (p less than 0.05) than those in venous samples (6.86 +/- 2.80 ng/mL). These results support that the arterial-venous gradient exists after administration of 6-chloro-2-pyridylmethyl nitrate in humans.
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PMID:Arterial-venous plasma concentration differences of 6-chloro-2-pyridylmethyl nitrate in humans after sublingual administration. 272 87

Isosorbide-5-mononitrate (IS-5-MN) is an active metabolite of isosorbide dinitrate with a longer plasma half life. Aim of the study was the evaluation of the effects of 40 mg/day of IS-5-MN on exercise capacity in patients with heart failure NYHA class II. After 1 week of wash-out, 10 patients with heart failure NYHA Class II, assumed 20 mg bid for 3 weeks. Bicycle ergometer tests were performed before (A), at the end of therapy (B), and 1 week later (C); in phase B the stress test was performed after 6 hours from the last assumption of IS-5-MN. We measured 24 hour urinary 6K-PGF1 alpha, the stable metabolite of prostacyclin, basal plasma renin activity (PRA) and plasma aldosterone, exercise-release of epinephrine and norepinephrine at the end of each phase of the study. The treatment with IS-5-MN improved the exercise capacity sigma (Watt.min), A less than (B = C), (p less than 0.01), while delta of heart rate (HR) during exercise (basal HR - maximal exercise HR)/(Watt.min), decreased, A greater than (B = C), (p less than 0.008). Basal BP and HR did not change. This fact seems consistent with the hypothesis of a combined effect of nitrates on both the venular and the arteriolar districts. Basal PRA and aldosterone, and catecholamine release during exercise after IS-5-MN did not change, while only norepinephrine increased 1 week after the end of the therapy, (A = B) less than C, (p less than 0.05): 24 hour urinary 6-K-PGF1 alpha increased after IS-5-MN A less than (B = C), (p less than 0.05). The results indicate that medium-term IS-5-MN treatment increases exercise capacity in patients with heart failure NYHA class II and that the effect lasts for 1 week after nitrate withdrawal at least. Prostacyclin is probably involved in medium-term clinical effect of IS-5-MN.
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PMID:[Effects of isosorbide-5-mononitrate on exercise capacity, prostacyclin synthesis, the renin-aldosterone axis and catecholamines in patients with cardiac insufficiency]. 275 47

We studied the hemodynamic effect of a single dose of the new direct-acting vasodilator, flosequinan, in ten patients with severe acute-onset heart failure complicating acute myocardial infarction (MI) resistant to high iv doses of diuretics, nitrates, and dobutamine. Flosequinan was added to conventional therapy at 3.8 +/- 0.5 days after infarction in the form of a single 100-mg oral dose. Hemodynamic measurements were performed every hour for 4 h after administration, without any other drug being added. The nitrate infusion rate was kept constant. Flosequinan produced hemodynamic improvement in this group. The effect peaked at 1 to 2 h and remained at this level at 4 h. Pulmonary capillary wedge pressure decreased from 27.2 +/- 5.4 to 16.4 +/- 3.0 mm Hg, and cardiac output increased from 3.5 +/- 0.3 to 4.1 +/- 0.4 L/min (p less than .001 for both). Cardiac index, stroke index, and left ventricular stroke work index were significantly increased. Pulmonary arterial and right atrial pressures, and systemic and pulmonary vascular resistances were also significantly reduced. Heart rate was not significantly altered. Mean systemic arterial pressure was slightly reduced. Flosequinan administration was not associated with symptomatic hypotension, cardiac arrhythmias, or other adverse events, and the hemodynamic effect was not related to the pretreatment serum sodium concentration. We conclude that flosequinan is effective in producing acute hemodynamic improvement in patients with heart failure complicating acute MI resistant to conventional therapy.
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PMID:Effect of flosequinan in patients with acute-onset heart failure complicating acute myocardial infarction. 276 58

Isosorbide dinitrate (ISDN) improves the clinical and hemodynamic state of patients with heart failure, but may cause dizziness and syncope. To characterize patients in whom cardiac output falls with high-dose nitrate therapy and to examine further the pathophysiology of the fall in cardiac output in these patients, we studies the effect of sublingual ISDN on forward cardiac output in 14 patients with severe cardiac failure (New York Heart Association grades 3-4). We examined systolic and diastolic left ventricular (LV) function from pressure and volume analyses of LV function. After administration of 15 mg ISDN, cardiac output was either unaltered or increased in 7 patients (Group 1) (11 +/- 12%, mean +/- SD), and decreased in 7 (Group 2) (-13 +/- 10%) (Group 1 vs. 2, p less than 0.002). Initial systemic arterial pressure, LV ejection fraction, wedge and LV transmural filling pressures were similar in both groups, but Group 2 patients had a lower systemic vascular resistance (p = 0.07) and tended to have a larger initial LV end-diastolic volume and increased end-diastolic compliance; following ISDN the decrease in LV filling pressure and end-diastolic volume was larger and the product of the changes greater (p less than 0.02). Thus ISDN decreases filling pressure and improves forward cardiac output in some patients with congestive heart failure, but large doses may decrease cardiac output in a subset of patients who have a lower systemic vascular resistance and a larger more compliant ventricle, maintaining forward blood flow predominantly by a preload reserve mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of isosorbide dinitrate on cardiac output in severe cardiac failure: relation to initial hemodynamics, ventricular volume, and the preload reserve mechanism. 279 73

Nitroglycerin has long been a mainstay of the treatment of ischemic cardiac pain. The introduction of transdermal formulations and in particular the development of controlled methods of delivery have been responsible for the renaissance of clinical interest in this simple and effective treatment. The pathophysiologic abnormality accompanying myocardial ischemia affords a natural theater for the exhibition of the therapeutic utility of these preparations and methods. The means whereby nitrates induce relaxation of vascular smooth muscle are not entirely clear, but their pharmacodynamic activities are perfectly plain. In the doses used in clinical practice, nitrates exert their predominant hemodynamic effects and therapeutic benefits through their peripheral vasodilator activities. This is particularly marked in veins, although in higher doses nitrates also dilate the larger systemic and coronary arteries. Criticisms of the efficacy of transdermal formulations of nitrates in the treatment of angina pectoris have arisen largely from uncritical acceptance of a small number of studies of questionable methodologic validity. Large-scale general practice studies have invariably found that transdermal nitrate delivery systems improve the quality of life in ambulant patients: anginal attacks are reduced with a minimum of side effects. The widespread acceptance of this novel form of drug delivery has stimulated its application in other therapeutic avenues. The efficacy of transdermal nitroglycerin in the suppression of silent ischemic attacks has been demonstrated. The maintenance of benefit initiated by intravenous nitroglycerin in patients with unstable angina also broadens the use of this method of nitrate delivery. In patients with acute myocardial infarction, whether complicated by left ventricular failure or not, the nitrates, and transdermal nitroglycerin in particular, appear to hold considerable promise. Improvement of hemodynamic abnormalities may cause reduction in infarct size and fewer life-threatening arrhythmias. Even survival may be extended. The utility of transdermal nitrates in the treatment of severe chronic heart failure is less certain. But the use of higher doses and an interval regimen of administration may hold promise for such patients. Naturally, more information is required before the overall therapeutic profile of this new method of controlled nitroglycerin delivery across the whole spectrum of coronary heart disease can be fully described. Fortunately, the high level of efficacy and safety of transdermal nitroglycerin demonstrated in the majority of reported studies encourages the pursuit of such an important therapeutic target.
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PMID:The role of transdermal nitroglycerin in the treatment of coronary heart disease. 308 57

To evaluate possible mechanisms underlying the development of nitrate tolerance, we treated 35 patients who had severe chronic heart failure with a prolonged (48-hour) intravenous infusion of nitroglycerin (6.4 micrograms per kilogram of body weight per minute) given either continuously or intermittently (12-hour infusions separated by intervals of 12 hours). Intravenous nitroglycerin produced immediate hemodynamic benefits in all patients, but the magnitude of this improvement was greatly diminished after 48 hours of continuous therapy with the drug. This attenuation was accompanied by cross-tolerance to oral isosorbide dinitrate and by an increase in heart rate, plasma renin activity, and body weight. In contrast, intermittent therapy with intravenous nitroglycerin was not associated with a loss of hemodynamic efficacy or cross-tolerance to oral nitrates and was not accompanied by changes in neurohormonal activity or body weight. In eight patients in whom nitrate tolerance developed during continuous intravenous therapy, the administration of the sulfhydryl-containing compound N-acetylcysteine (200 mg per kilogram orally) restored the hemodynamic state toward that observed at the start of the infusion of nitroglycerin (partial reversal of tolerance). In contrast, N-acetylcysteine had little hemodynamic effect in patients who were not receiving nitroglycerin. These data support the hypothesis that neurohormonal activation and depletion of sulfhydryl groups may interact to cause the loss of hemodynamic efficacy that occurs during prolonged treatment with intravenous nitroglycerin in patients with heart failure. Evaluation of the suggested role of sulfhydryl depletion in the development of tolerance will, however, require direct studies of vascular tissue.
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PMID:Prevention and reversal of nitrate tolerance in patients with congestive heart failure. 311 37

The systemic vasoconstriction that is characteristic of patients with congestive heart failure involves arteriolar constriction, reduction in arterial compliance and reduction in venous capacitance, all of which contribute to the increased impedance and increased preload that aggravate the hemodynamic abnormality. Nitrates are effective in increasing arterial compliance and venous capacitance and thus have a favorable acute hemodynamic effect in heart failure. Long-term studies suggest that this favorable effect is maintained in response to high dose oral isosorbide dinitrate therapy and that it is associated with relief of symptoms and improved exercise tolerance. When combined with hydralazine, isosorbide dinitrate therapy has been shown in the Veterans Administration study to prolong survival in patients with class II and III congestive heart failure. Therefore, long-term nitrate therapy appears to have an important potential in patients with heart failure. It may now be appropriate to use nitrates not only to relieve symptoms, but also to improve long-term outlook in this syndrome.
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PMID:Role of nitrates in congestive heart failure. 312 May 64

Altogether 70 patients suffering from CHD with attacks of angina of effort received propranolol and syndnopharm therapy in an outpatient clinic. After therapy a positive clinical effect was noted in 83.6% of the patients, a positive ECG time course in 64.2%. The combined use of both drugs increased their efficacy. The combination was justified in case of nitrate intolerance and the absence of marked heart failure.
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PMID:[Effectiveness of combined administration of obsidan and sidnofarm in patients with ischemic heart disease at a polyclinic]. 336 98

The anaerobic threshold (AT) has been proposed as an index to assess the functional status of patients with chronic heart failure. The focus of this report was to evaluate in post-myocardial infarction patients the utility of the AT for (a) assessing the severity of exercise-induced left ventricular impairment, (b) determining the responses obtained from different treatments and (c) prescribing exercise training. We found that the AT level was lower in patients with abnormal haemodynamic patterns during exercise. The AT was correlated to different degrees of exercise-induced left ventricular impairment. The nitrate and calcium-antagonist effects have been evaluated in patients with abnormal exercise haemodynamics. The resting and exertional results were in agreement with the vasodilator effects. Moreover, the time from onset of exercise to the appearance of the AT was significantly increased by the treatments. Thus, AT during pharmacological treatments may be a non-invasive useful parameter for assessing their haemodynamic effects. Finally, a 4-week intermittent training programme based on AT level was evaluated in patients with abnormal resting and exertional haemodynamics. The results showed an improvement of the exercise cardiovascular tolerance without negative effects on left ventricular function. Therefore, the AT seems to be useful when prescribing a rational and individualized training programme.
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PMID:Does the study of anaerobic metabolism give quantitative information on left ventricular dysfunction during exercise? 339 Nov 81


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