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

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

The action of isorsorbide-5-mononitrate (IS-5-MN) infusion (range 6.0 to 10.0 mg/hour) was studied in 24 patients with and without acute heart failure (hemodynamic subsets I to IV) during acute myocardial infarction. Hemodynamic measurements were performed by right-sided cardiac catheterization. Intravenous IS-5-MN demonstrated significant hemodynamic effects compared with baseline values. In subsets I and II, a decrease in pulmonary wedge pressure (PWP) and in cardiac index (CI), without significant changes in heart rate, mean arterial pressure or systemic vascular resistance index were demonstrated. In subsets III and IV, a major increase in CI and a decrease in systemic vascular resistance index, as well as a decrease in PWP were found. Again no changes occurred in mean arterial pressure and heart rate. The dosage was similar in subsets I to IV (8.0, 7.9, 7.8 and 7.3 mg/hour); thus, the differences in the responses could not be attributed to dosage. It appears that several different patterns of hemodynamic IS-5-MN action exist, assuming that IS-5-MN operates on preload and afterload levels. The action of IS-5-MN mechanisms seems to be dependent on an initial hemodynamic subset. No patient had any deleterious hemodynamic effects. A decrease in CI in subsets I and II was not of clinical importance with these dosages. No nitrate tolerance during 9.0 hours of continuous therapy appeared.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous isosorbide-5-mononitrate in the treatment of acute myocardial infarction. 219 Apr 63

The haemodynamic influence of positive inotropic therapy with dobutamine, both alone and when combined with isosorbide dinitrate, was evaluated in 10 consecutive patients admitted to Coronary Care with acute left ventricular failure (pulmonary artery occluded pressure greater than 20 mm Hg) complicating myocardial infarction. Dobutamine increased systemic arterial blood pressure and heart rate without reduction in the left heart filling pressure; cardiac index (+0.9 L/min/m2; p less than 0.01) was substantially increased. Thus, consequent on these effects, dobutamine could increase myocardial oxygen requirements. The addition of intravenous isosorbide dinitrate reduced systemic arterial pressure and left heart filling pressure; the augmented cardiac index following therapy with dobutamine alone was maintained. Combined dobutamine/nitrate therapy, therefore, appeared haemodynamically superior to dobutamine monotherapy, in that it improved cardiac stroke volume at a normalised left ventricular filling pressure. These data suggest that combined dobutamine/nitrate therapy may prove useful as an adjunct to the treatment of normotensive heart failure complicating acute myocardial infarction.
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PMID:Haemodynamic advantages of a combined inotropic/venodilator regimen over inotropic monotherapy in acute heart failure. 241 5

Recent evidence from the Veterans Administration Vasodilator Heart Failure Trial supports the prophylactic use of a combination of hydralazine and isosorbide dinitrate to prolong life in patients with congestive heart failure. The clinical utility of such a combination vasodilator regimen may be limited, however, by its high frequency of adverse reactions, the lack of evidence that such a regimen enhances exercise tolerance, the inconvenience of taking a large number of tablets daily for a prophylactic indication, and the dearth of clinical experience combining hydralazine-nitrate with agents that may be clinically indicated to produce long-term symptomatic benefits (i.e., converting-enzyme inhibitors). Controlled evidence in animals and uncontrolled evidence in humans suggest that converting-enzyme inhibitors may also favorably modify prognosis, perhaps by antagonizing the deleterious actions of endogenous neurohormonal systems. Trials (presently in progress) are designed to evaluate the hypothesis that converting-enzyme inhibitors exert beneficial effects on the survival of patients with congestive heart failure comparable to those reported with hydralazine and isosorbide dinitrate.
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PMID:Can we expect vasodilator therapy to prolong life in patients with congestive heart failure? 244 Dec 5

The haemodynamic effects of a transdermal nitroglycerin delivery system (NTG-TTS) were investigated in 67 patients with a recent myocardial infarction. The study objectives were to define the dose-response effects of NTG-TTS and to examine the influence of baseline haemodynamic status on subsequent response. Therefore, patients with normal cardiac function [pulmonary artery occluded pressure (PAOP) less than 18 mm Hg, n = 40] and those with acute heart failure (PAOP greater than 18 mm Hg, n = 27) were studied after one of three regimens (TTS-10, TTS-20, or TTS-40) with the intention of securing 10 evaluable patients in each group. In patients with acute heart failure, all three doses reduced the left ventricular filling pressure with a modest decrease in systemic arterial pressure; cardiac index and heart rate were unaltered. The systemic vascular resistance was significantly reduced from 120 min. In patients with normal left ventricular function, there were small but significant reductions in systemic arterial pressure and vascular resistance with limited increases in heart rate; the cardiac stroke work index was reduced. These results are compatible with actions of NTG-TTS mainly on capacitance vessels; PAOP fell with limited impact on systemic arterial pressure and vascular resistance index. This mode of nitrate delivery resulted in a low incidence of hypotension and side-effects; comparison with other delivery methods in myocardial infarction seems indicated.
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PMID:Haemodynamic dose-response effects of a transdermal nitrate delivery system in acute myocardial infarction with and without left heart failure. 245 8

The mechanisms responsible for the development of nitrate tolerance are not completely clear, and their clinical importance remains controversial. This study examined the possible development of nitrate tolerance under the continuous infusion of high doses (10 mg/h) of nitroglycerine (NTG) and the effect of an additional N-acetylcysteine (NAC) injection in respect of hemodynamic changes. Eighteen patients with severe chronic heart failure (NYHA stages III-IV) were investigated. In 16 patients, NTG produced a marked improvement of the hemodynamic parameters; in two patients it caused a moderate amelioration only. In 13 patients there was a complete loss of the initial hemodynamic effect of NTG within 12 to 36 h. NAC reversed the NTG tolerance in 11 out of the 13 patients. In the two patients who showed a milder response to NTG and who did not develop a tolerance, NAC improved the effectiveness of NTG significantly. There was no additional NAC effect in the three patients without NTG tolerance. NAC itself produced no hemodynamic changes. These results confirm the relevance of the depletion of sulfhydryl-groups for the development of nitrate tolerance under the continuous infusion of NTG.
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PMID:[Nitrate tolerance and its management by N-acetylcysteine (studies of patients with severe chronic heart failure)]. 249 91

An open randomised parallel group comparison of the haemodynamic effectiveness of three different routes of nitrate administration was undertaken in 36 male patients aged 40-69 years who had developed acute left ventricular failure within 18 h of the onset of myocardial infarction. All patients had electrocardiographic and serum cardiac enzyme changes compatible with transmural myocardial infarction and all had both radiographic and haemodynamic evidence of left ventricular failure. None were hypotensive, all were in sinus rhythm and none were receiving other cardioactive drugs. Control haemodynamic measurements were made over a period of one h, following which patients were randomised to receive either intravenous isosorbide dinitrate (mean dose 12.9 mg; range 7.7-14.9), buccal nitroglycerine (5 mg) or transdermal nitroglycerin (nitro TTS 10). The raised left heart filling pressure was reduced by all nitrate preparations but none significantly changed the heart rate or cardiac output. Systemic arterial pressure and vascular resistance were reduced by i.v. ISDN and buccal NTG but not by a transdermal NTG. The only adverse circulatory reaction was hypotension in the three patients following buccal NTG. Nitroglycerin by the transdermal route appears to be equally effective in reducing the raised left heart filling pressure in patients with postinfarction heart failure without the practical disadvantages of monitoring its intravenous administration or the potential hazard of hypotension with buccal NTG.
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PMID:Haemodynamic comparison of different routes of nitrate administration in postmyocardial infarction left ventricular failure. 251 87

The clinical efficacy of xamoterol, alpha beta 1-adrenoceptor partial agonist, was determined in a multicentre double-blind, randomized, parallel group study of 240 patients with mild to moderate heart failure. At entry, 62% of patients were receiving diuretics (thiazides, or loop diuretics at a dose no greater than the equivalent of 80 mg of frusemide); 32% were taking nitrate formulations and 14% digoxin for control of atrial fibrillation. Assessments were carried out after a 1-week placebo run-in and after 3 months of treatment with either xamoterol or placebo. 198 patients completed the study of whom 186 had valid exercise tests. Mean exercise duration increased by 7% after placebo and by 19% after xamoterol during a progressive treadmill exercise protocol. Xamoterol significantly reduced peak exercise heart rate compared with placebo. Subjectively, there was improvement in breathlessness on the visual analogue scale after treatment with xamoterol compared with placebo, but no change in fatigue. We conclude that xamoterol produces sustained improvement in symptoms and exercise duration in mild to moderate heart failure.
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PMID:Clinical efficacy of xamoterol, a beta 1-adrenoceptor partial agonist, in mild to moderate heart failure. U.K. Xamoterol Study Group. 257 8

The authors describe the development of nitrates from substances of the first generation (nitroglycerin and isosorbide dinitrate) to the use of mononitrates. They explain the mechanism of their action, the haemodynamic effects and the phenomenon of nitrate tolerance. The authors present also their own experience with nitrate therapy in angina pectoris and heart failure based on haemodynamic monitoring and recommend its rational use.
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PMID:[The development and use of nitrate therapy]. 262 Mar 35

Organic nitrates are well established in the treatment of a wide variety of cardiovascular disorders, most notably angina pectoris and congestive heart failure. However, attenuation of, or tolerance to, haemodynamic and anti-ischaemic effects may occur with all long-acting nitrate formulations. In the majority of patients continuous administration of long acting nitrates tends to promote the development of attenuation, while intermittent administration avoids it. Likewise, higher-doses appear to induce attenuation to a greater degree than lower doses. Attenuation of haemodynamic effects and exercise tolerance in heart failure patients, and of clinical end-points in angina patients, appears to be less than attenuation of exercise testing end-points in angina patients. While the use of intermittent therapy avoids the development of attenuation, it may expose the patient to an as yet undefined risk of silent and/or symptomatic anginal episodes occurring during the nitrate-free interval. Likewise, the role of concomitant therapy in avoiding this potential risk remains to be defined. Means of avoiding attenuation may include the coadministration of sulfhydryl donors such as N-acetylcysteine. Alternatively, angiotension-converting enzyme (ACE) inhibitors such as captopril may block renin-angiotensin system-induced reflex sympathetic stimulation. Attenuation may occur to a greater or lesser degree in individual patients. The proportion of attenuators vs non-attenuators remains to be defined, as does a means of identifying such patients prospectively by clinical and/or laboratory parameters. Conflicting results among smaller studies may reflect variable proportions of attenuators vs non-attenuators. However, conflicting results among larger studies may reflect differences in patient selection criteria, such as selecting patients with positive and reproducible stress tests and little in the way of spontaneously occurring angina versus selecting patients with positive but variable stress tests and frequent episodes of spontaneously induced angina. The former group may reflect pure fixed coronary artery disease with little in the way of vasospasm, or change in vasomotor tone, while the latter group may reflect greater variability in vasomotor tone and/or more in the way of plaque instability. The clinical efficacy of long acting nitrates might therefore be expected to be greatest in those patients with larger numbers of spontaneously occurring angina episodes. Recent data suggest that nitrates may have important direct effects on coronary vessels including dilating eccentric coronary stenoses, dilating intercoronary collateral channels and having greater dilating effects on more diseased segments as opposed to less diseased coronary segments.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nitrate tolerance. A review of the evidence. 266 Nov 97


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