Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During exercise in subjects with congestive heart failure and mitral regurgitation the rise in systemic arterial pressure is usually accompanied by increase in systemic vascular resistance. That could cause decrease of cardiac output not only because of a lack of myocardial reserve, but also because of an increase of mitral regurgitant volume. In such situation decrease in left ventricular preload could further increase the regurgitant volume and cardiac output. Whether changes in pre-or afterload can cause significant changes in mitral regurgitation, nitroglycerin and phentolamine was assessed in that group of patients. 22 patients with significant mitral regurgitation (3+,4+) was randomly divided into two groups. The first one received short intravenous infusion of nitroglycerin at a rate of 170 micrograms/min. The second one received phentolamine intravenously 1-1,5 mg/min. Patients underwent right heart catheterization with Swan-Ganz thermodilution catheter. Mean pulmonary, pulmonary capillary wedge, and right atrial pressure were monitored and recorded. Cardiac output was determined by thermodilution technique using iced 5% dextrose. If there were no contraindications (PWP greater than 30 mm Hg) an effort test was performed (cycloergometer, supine position). The same protocol was repeated during administration of nitroglycerin and phentolamine. Nitroglycerin significantly decreased right atrial and capillary wedge pressure (from 22.9 to 15.6 mm Hg). There were no significant differences in cardiac output, pulmonary and systemic vascular resistance. Pulmonary artery pressure decreased after nitroglycerin but the difference was not significant. All above effects of nitroglycerin persisted during effort. Phentolamine decreased significantly right atrial, pulmonary and capillary wedge pressure with simultaneous increase of cardiac output (30%) and decrease of pulmonary and systemic vascular resistance. In summary, nitroglycerin decreases only symptoms and theoretically could worsen forward flow in patients with mitral regurgitation and heart failure, especially in subjects with a significant increase of systemic vascular resistance during effort.
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PMID:[Effect of intravenous administration of nitroglycerin and regitine on hemodynamics in mitral valve insufficiency]. 212 94

Plasma levels of nitroglycerin were measured 13 to 24 hours after the application of nitroglycerin stamps in 7 children aged from 1 month to 7 years and suffering from heart failure. The plasma levels varied considerably from one patient to another, confirming that the bioavailability of transdermal nitroglycerin is extremely variable in children. Only 3 patients had a nitraemia higher than 1 ng/ml, a figure compatible with a haemodynamic effect of the drug. No side-effect associated with the nitroglycerin stamps was observed. The dosage we use (a quarter of a stamp for 5 kg bodyweight) seems to be adequate at the beginning of treatment, to be progressively increased according to the way the drug is tolerated.
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PMID:[Transcutaneous transport of trinitrin in children after application of nitroglycerin patches]. 214 54

It has been shown that renal responses to atrial natriuretic peptide (ANP) are markedly attenuated in patients with heart failure. This study aimed to determine if vasodilative response to ANP is altered in patients with heart failure. In patients with heart failure (n = 7) and age-matched normal subjects (n = 7), forearm blood flow was measured using a strain-gauge plethysmograph during intra-arterial infusion of alpha-human ANP (50, 100, 200, and 400 ng/min) or nitroglycerin (100, 200, 400, and 600 ng/min). Forearm vasodilatation evoked with intra-arterial alpha-human ANP in patients with heart failure was considerably less (p less than 0.01) than that in normal subjects. In contrast, nitroglycerin produced comparable forearm vasodilatation in the two groups. Plasma ANP and cyclic guanosine monophosphate (GMP) levels at rest were higher in patients with heart failure than in normal subjects (p less than 0.05 for both), but the increases in plasma ANP and cyclic GMP in the venous effluents during intra-arterial ANP infusion did not differ between the two groups. These results indicate that the direct vasodilative effect of ANP on forearm vessels was attenuated in patients with heart failure as compared with that in normal subjects. The mechanisms responsible for this alteration are not clear but might involve mechanisms other than down-regulation of the ANP receptors because the increases in venous plasma cyclic GMP caused by intra-arterial ANP were comparable between patients with heart failure and normal subjects.
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PMID:Attenuated forearm vasodilative response to intra-arterial atrial natriuretic peptide in patients with heart failure. 216 79

We have conducted a randomized, double-blind, placebo-controlled multicentre trial of oral isosorbide 5-mononitrate (ISMN) in 360 patients with suspected acute myocardial infarction. Patients were stratified prior to analysis according to the presence or absence of left ventricular failure on admission. ISMN caused a significant reduction in systolic and diastolic blood pressure during the first 12 h. There was no significant effect on heart rate. Overall mortality was 4.9% in the ISMN group compared with 4.0% in controls at 5 days, and 14.1% compared with 10.5% at 6 months (NS). A non-significant reduction in mortality in the ISMN group with heart failure (ISMN 7.9%, placebo 12.9%, at 5 days) contrasted with a non-significant increase in mortality in patients without heart failure treated with ISMN (ISMN 4.1%, placebo 2.1%, at 5 days). Lignocaine was used in twice as many patients in the ISMN group as in placebo group (P less than 0.01), both with and without heart failure. Diamorphine usage was similar in the ISMN and control groups. Oral ISMN has similar haemodynamic effects to intravenous nitroglycerin, and can be of benefit in acute myocardial infarction with heart failure. However, our results question the use of nitrates in acute myocardial infarction in the absence of heart failure.
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PMID:The effects of oral isosorbide 5-mononitrate on mortality following acute myocardial infarction: a multicentre study. 237 4

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

In canine and porcine coronary arteries, experimental atherosclerosis (induced by endothelial denudation followed by a high-cholesterol diet) potentiates the vasoconstrictor effects of histamine, serotonin, and ergonovine. In isolated human atherosclerotic coronary arteries, only hypersensitivity to histamine has been demonstrated. This discrepancy could be due to several factors. First, the atherosclerotic lesions in human vessels are different from those observed in the animal, since experimental atherosclerosis often corresponds only to the early stage of the disease in humans. Second, the human atherosclerotic coronary arteries were isolated mainly from patients with cardiac failure, a condition that alters the responses of coronary smooth muscle to vasoactive amines. With regard to endothelium-dependent vasodilators, marked attenuations of the relaxations to substance P, bradykinin, and the Ca2+ ionophore A23187 have been described in isolated human atherosclerotic arteries. Acetylcholine elicits variable responses in these preparations and even if the arteries are devoid of atherosclerotic lesions, it often fails to relax them. In addition to this endothelial dysfunction, severely atherosclerotic human coronary vessels exhibit a slightly decreased responsiveness to nitroglycerin and SIN-1 but not to forskolin. Another abnormality of the smooth muscle is a marked attenuated beta-adrenergic relaxation. Thus, atherosclerosis of human coronary vessels induces not only marked alterations in endothelium-dependent responses but also modifies the sensitivity to several endothelium-independent vasodilators.
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PMID:Atherosclerosis and responses of human isolated coronary arteries to endothelium-dependent and -independent vasodilators. 248 97

Heart failure may have repercussions on the different stages of pharmacokinetics. Following intramuscular or oral administration, drug absorption may be slowed down by the fall in cardiac output and by peripheral vasoconstriction. Tissue distribution is altered by changes in the plasma protein binding of drugs and by redistribution of cardiac output to the brain and heart, resulting in changes in the apparent volume of distribution. Excretion through the liver is influenced by the decrease of hepatic blood flow and metabolic capacities. Lowering of the renal blood flow alters the glomerular and tubular excretion processes. These hepatic and renal dysfunctions result in a reduction of total plasma clearance. The effects of heart failure on the pharmacokinetics of digitalis compounds seem to consist merely of a delay in digestive tract absorption. More studies have been devoted to the fate of antiarrhythmic agents. Blood concentrations of lidocaine are raised in patients with heart failure; this is accounted for by the redistribution of local blood flows, the increase in plasma protein binding observed after myocardial infarction and the reduced hepatic clearance. A fall in the volume of distribution and total clearance of quinidine has been described. Data concerning disopyramide are discordant, but reduction of the free drug fraction and variations in total clearance have been observed after myocardial infarction. Alterations in the total clearance of prazosin, nitroglycerin and theophylline have been reported by several authors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of cardiac insufficiency on pharmacokinetics]. 250 96

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

Nirmin, a novel dosage form of nitroglycerin, was used to treat heart failure in 47 patients on days 1-3 after acute myocardial infarction. The drug was intravenously injected at 12-400 micrograms/min for 3-24 hours. Central hemodynamic changes were evaluated from equilibrium radionuclide ventriculographic data and pulmonary diastolic and central venous pressures. Nirmin improved the clinical status in 89.3% of the patients. Hemodynamic effects of the agent were manifested by reduced myocardial preload and its improved contractility, followed by elevated left ventricular ejection fraction and decreased hypokinesia of the myocardial affected areas.
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PMID:[Effects of nirmin on central hemodynamics in patients with heart failure in the acute period of myocardial infarct]. 251 10

Fourteen patients suffering from severe heart failure with 18 mmHg or higher diastolic pulmonary arterial pressure were given a transdermal therapeutic system of nitroglycerin (TTS-NTG). They were evaluated for changes in the hemodynamic responses over 24 hours. Diastolic pulmonary arterial pressure decreased from 27.1 +/- 2.3 mmHg (mean +/- SE) to 22.4 +/- 1.7 mmHg after 1 hour (p less than 0.01), which was maintained throughout the trial. Cardiac index increased from 2.42 +/- 0.13 l/min/m2 to 2.64 +/- 0.16 l/min/m2 after 1 hour (p less than 0.01). The analysis of cardiac and vascular function curves in individual patients suggested that the improvement of hemodynamics was induced mainly in six patients with an increase of contractility and in four patients with a reduction of afterload. No changes were observed in three patients in either contractility or afterload, and a decrease in contractility was seen in one patient. These results suggest that TTS-NTG can be transcutaneously absorbed well enough to produce improved hemodynamic responses in patients with severe heart failure by several mechanisms and maintain these effects over 24 hours.
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PMID:Effects of transdermal therapeutic system-nitroglycerin in patients with heart failure. Influence on hemodynamic changes. 251 42


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