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

Transdermal nitroglycerin becomes more and more common mode of pharmacotherapy as this form of nitroglycerin ensures permanent therapeutic level of the drug in the blood serum for a long time. The largest clinical experience with transdermal nitroglycerin has been gathered in effort angina although it is used in all forms of ischemic heart disease. It has been documented that transdermal nitroglycerin improves exercise tolerance, increases pain threshold, delays the onset of ST segment depression in the ECG and decreases the incidence of anginal attacks. Beneficial effects of transdermal nitroglycerin on hemodynamic parameters have been shown also in patients with myocardial infarction, especially complicated by heart failure. First results obtained in the treatment of silent myocardial ischemia are very promising. The development of tolerance requires 12-hour intervals in the use of nitroglycerin patches.
 ...
PMID:[Transdermal use of nitroglycerin]. 251 62

We measured increments of peripheral venous pressure induced by dynamic leg exercise (delta VP) in 10 healthy subjects (Group C) and 70 patients with heart diseases which primarily affect the left-side of the heart. None of the subjects showed apparent symptoms of left- or right-sided heart failure. The patients were divided into 2 groups on the basis of delta VP, namely, Group N (delta VP less than 35 mmH2O, n = 30, normal reaction) and Group H (delta VP greater than or equal to 35 mmH2O, n = 40, abnormal reaction). We measured the increments of plasma concentrations of noradrenaline (delta NAPH) and adrenaline (delta APH) with infusion of phentolamine (PH). Parallel studies with nitroglycerin and prazosin supplied strong evidence that delta NAPH was brought about mainly by the blockade of alpha 2-receptors at the sympathetic nerve terminals. Thus, we estimated the degree of sympathetic nerve activity from the central nervous system by opening using PH the negative feed-back loop for noradrenaline (NA) release at the sympathetic nerve terminals, and this degree of sympathetic nerve activity was compared with the degree of delta VP. The results obtained were 1) there was a rough overall correlation between delta VP and delta NAPH in the subjects of Groups C, N and H, and 2) delta NAPH was significantly higher in Group H than in Groups C and N. These results suggest that much reliance can be placed on the measured increment of plasma NA concentration in response to the administration of PH in assessing the degree of enhanced sympathetic nerve activity in the patients with "latent" left-sided heart failure.
 ...
PMID:Increase in plasma noradrenaline concentration after the administration of phentolamine in the patients with "latent" left-sided heart failure. 256 Nov 61

The effects of i.v. nitroglycerin were studied by ECG and enzymatically in 16 patients (mean age 57.9 +/- 1.4 years) (NTG) in comparison with a control lot (c) of 17 patients (mean age 62.7 +/- 2.1 years) treated with dipyridamole and/or nifedipine (N), admitted in the first 4-10 hours after the onset of the first symptoms. The patients with heart failure and those with Q waves and CPK or LDH values greater than 2 x n were not admitted. NTG was administered in doses of 20 micrograms--60 microgram/hour for 24-96 hours and systolic AT (s) was kept under 10% of the basic values but not under 100 mmHg. Myocardial infarction appeared in 9 N-treated patients (54.86%) and 11 controls (58.25%) (p = 0.07). The size of myocardial necrosis was reduced in the N-treated patients. Peak serum CPK levels had considerably less increases in N (from 72.9 U to 73.4 U) (p greater than 00.5) versus C from 34.2 U to 364.5 U) (p less than 0.001). The sum of segmentary depression failed from 9.13 mm to 3.19 mm (p less than 0.05) in N, whereas in C the decrease was not significant (6.12 mm as against 9.38 mm; p greater than 0.05). The evolution was severe in C, as the angina crises (14 cases versus 2 cases, p less than 0.01) and the extension of the infarction (8 cases versus, 0; p 0.05) less than 0.05) appeared more frequently than in N. Only two patients in C died (p less than 0.05). Therefore, i.v. NTG administration in small doses in acute myocardial infarction leads to immediate disappearance of the anginal pain, lowers the extent of the myocardial necrosis and improves the clinical evolution.
 ...
PMID:[The effects of nitroglycerin administered intravenously in acute myocardial ischemia]. 257 23

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.
 ...
PMID:[The development and use of nitrate therapy]. 262 Mar 35

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.
 ...
PMID:The clinical significance of nitrate tolerance in patients with chronic heart failure. 266 3

Vascular responses to many physiological stresses are abnormal in heart failure. Increased peripheral resistance and a reduction in the vasodilator response to exercise and ischemia are examples of this abnormal vascular control. Such abnormal vascular control in heart failure is a result of interplay between neural, hormonal, and local vascular factors. This study was designed to test the hypothesis that a specific local mechanism, endothelium-dependent relaxation to acetylcholine (ACh), is depressed in experimental heart failure. Experiments were performed on 11 purebred beagles. Experimental heart failure was induced by rapid ventricular pacing for approximately 30 days. Femoral artery diameter was measured by sonomicrometry, and dose-response relationships to ACh, norepinephrine (NE), and nitroglycerin (NTG) were done before and after inhibition of cyclooxygenase by indomethacin. Heart failure resulted in a significant depression of ACh relaxation at all concentrations. In dogs with heart failure, indomethacin enhanced the dilation response to low concentrations of ACh. Constriction to NE and dilation to NTG were unchanged by heart failure. These data demonstrate that in the canine femoral artery endothelium-dependent dilation to ACh is depressed in experimental heart failure. Depression of endothelium-dependent vasodilation represents one local mechanism for abnormal control of the vasculature in congestive heart failure.
 ...
PMID:Heart failure depresses endothelium-dependent responses in canine femoral artery. 270 66

Prolonged administration of nitroglycerin and its derivatives results in pharmacodynamic tolerance: although the dosage of these drugs is kept at the same level, their therapeutic effects decrease in amplitude. Experimental and clinical studies have shown that this escape phenomenon is due to depletion of cysteine in the vascular wall. This amino acid, which gives off SH radicals, is indispensable to the ultimate transformation of nitroglycerin enabling in to exert its vasodilator action. Molsidomine does not require any transformation to act on the vascular smooth muscle and should therefore remain insensitive to tolerance. The experimental and clinical data available at present seem to confirm that the effects of molsidomine administered for long periods in the treatment of coronary disease and heart failure are sustained. However, for the long-term effectiveness of molsidomine and nitrites to be compared objectively a prospective double-blind randomized trial would be needed, with both treatments being in optimal doses and intervals of administration.
 ...
PMID:[Comparative course of maintenance of the effects of nitrite derivatives and molsidomine after prolonged administration]. 296 4

We have reported early attenuation of hemodynamic effects of transdermal nitroglycerin in patients with heart failure. We now report nitroglycerin plasma levels in those same patients. We administered transdermal nitroglycerin, 60 mg/24 h, to eight patients or placebo to seven patients in a double-blind fashion, and monitored pulmonary wedge pressure and nitroglycerin plasma levels for 24 hours. After placebo administration, nitroglycerin plasma levels and pulmonary wedge pressure remained unchanged. During transdermal nitroglycerin administration, the plasma nitroglycerin level rose from 0.04 +/- 0.12 ng/mL at baseline to near peak levels at 2 hours (7.43 +/- 7.21 ng/mL). Between 2 and 24 hours, levels fluctuated at a steady state. Pulmonary wedge pressure fell from 22 +/- 7 mm Hg at control to a nadir of 14 +/- 5 mm Hg at 4 hours (p less than 0.01). Despite persistently high plasma nitroglycerin levels, by 18 hours pulmonary wedge pressure was no longer significantly reduced (20 +/- 9 mm Hg). These results indicate that rapid development of tolerance is the cause of attenuated hemodynamic efficacy of transdermal nitroglycerin.
 ...
PMID:Rapidly developing tolerance to transdermal nitroglycerin in congestive heart failure. 308 Sep 35

The hemodynamic effects following an oral dose of 19.5 mg of nitroglycerin microencapsulated to give prolonged release have been studied in 10 patients during the 48 hours which followed the establishment of a myocardial infarct complicated by moderate left cardiac insufficiency. The right auricular pressure and the pulmonary capillary pressure diminished significantly 20 minutes after the dose; 4 hours later the persistence of these effects is significant. A transient diminution of the systolic arterial pressure was observed initially (p less than 0.05). We observed that the cardiac index tends to increase although the increase did not attain the threshold of significance. No difference was observed in cardiac frequency, diastolic and mean arterial pressure and in the systemic vascular resistance. We conclude that in the patient presenting an acute myocardial infarct, 19.5 mg of NTG, microencapsulated to give prolonged release, essentially produce a reduction of the preload, with an early onset of action and a hemodynamic efficacy lasting at least 4 hours.
 ...
PMID:[Hemodynamic effects of microencapsulated delayed-release nitroglycerin in acute myocardial infarction]. 308 72

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.
 ...
PMID:The role of transdermal nitroglycerin in the treatment of coronary heart disease. 308 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>