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)

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

The effect of 4 mg Molsidomine iv. followed by a continuous infusion of 3 mg per hour for 3 hours on arterial blood pressure, pulmonary artery pressure, cardiac index, peripheral and pulmonary vascular resistance and heart rate was evaluated in eleven patients suffering from chronic heart failure caused by non-ischaemic dilatative cardiomyopathy (NYHA II-III). A significant decrease in systemic blood pressure, systolic and mean pulmonary artery pressure and pulmonary wedge pressure was observed and also a marked decrease in total peripheral and pulmonary vascular resistance. There was a slight, but not significant increase in cardiac index. The heart rate did not change significantly. Treatment had to be stopped in one patient because of side effects (hypotension, nausea).
 ...
PMID:[Effect of molsidomine on hemodynamics in patients with dilated cardiomyopathy]. 376 47

The effects of molsidomine were studied in seven patients with refractory congestive heart failure by means of two-dimensional echocardiography. Four milligrams of molsidomine or placebo was sublingually administered in a double-blind crossover manner. End-diastolic dimension, end-systolic dimension, and mean velocity of circumferential fiber shortening were measured just below the mitral valve before drug or placebo administration and 1 hour later. No significant changes were observed with placebo. Heart rate and mean arterial pressure were not significantly modified with Molsidomine (80 to 83 bpm and 100 to 97 mm Hg, respectively). The reduction in end-diastolic dimension (67 to 61 mm; 9%; P less than 0.01) was slightly greater than the decline in end-systolic dimension (59 to 54 mm; 8%; p less than 0.01). The mean velocity of circumferential fiber shortening increased from 0.4 to 0.5 sec-1 but did not achieve statistical significance. Thus sublingual administration of molsidomine in patients with chronic heart failure reduces end-diastolic more than end-systolic dimension without effect on blood pressure, suggesting a predominant action on cardiac preload.
 ...
PMID:Effects of molsidomine on left ventricular dimensions and cardiac function in patients with chronic heart failure. 383 5

In this report we present the results of hemodynamic monitoring with a Swan-Ganz balloon catheter in 14 patients with heart failure associated with acute myocardial infarction, before and during 8 hours after a single oral dose of molsidomine (6 mg). Molsidomine induced the following changes: heart rate was reduced between 1.6% and 4.7% (significant at 4 hours, p less than 0.05); systolic blood pressure decreased 8.4% at 1 hour (p less than 0.05); pulmonary capillary pressure decreased approximately 30% (significant and lasting until 8 hours after administration, p less than 0.002); cardiac index did not change significantly, although individual analysis showed an increase in 6 of 12 cases; stroke volume index increased by 6% (significant at 1 hour, p less than 0.025); and left ventricular stroke work index increased from 9.8% to 24.5% (significant at 1 and 4 hours, p less than 0.01 and 0.025). These findings show the beneficial hemodynamic effects of molsidomine in patients with heart failure complicating acute myocardial infarction.
 ...
PMID:Molsidomine in the treatment of acute heart failure. 383 9

We measured over a 2-h period the effects of molsidomine (0.5 mg/kg i.v.) on pulmonary artery and left ventricular (LV) end-diastolic pressures and internal heart dimension (preload), LV systolic and peripheral blood pressures and total peripheral resistance (afterload), and heart rate, LV dP/dt, stroke volume, and cardiac output (heart performance) of dogs anesthetized with pentobarbital. The hemodynamic effects of molsidomine were influenced by intravenous infusion of 0.10 or 0.20 micrograms/kg/min norepinephrine or 3 or 6 micrograms/kg/min dopamine. Molsidomine decreased preload, stroke volume, and cardiac output for over 2 h and ventricular and peripheral pressures for 45 min. Peripheral resistance, heart rate, and LV dP/dtmax were not altered. Low doses of norepinephrine and dopamine reversed the effect of molsidomine on afterload. However, neither catecholamine influenced the reduced end-diastolic filling pressure after molsidomine. The diminished stroke volume was elevated by either catecholamine so that cardiac output eventually increased. These results indicate that both norepinephrine and dopamine can reverse the certain effects of intravenously administered molsidomine, probably by increasing cardiac contractile force, cardiac output, and peripheral resistance. A combination of molsidomine's preload lowering effects with dopamine's effects on afterload may be useful for the treatment of patients with myocardial failure.
 ...
PMID:Effects of catecholamines on cardiovascular actions of molsidomine in anesthetized dogs. 619 Nov 51

In the face of the recent introduction of beta-blockers and calcium inhibitors, the author examines the role of Amiodarone, Perhexiline and Molsidomine in the treatment of angina pectoris. Amiodarone, introduced in 1967, remains a very useful anti-anginal drug. The beta and alpha-sympathetic inhibition it produces, makes it effective in effort and resting angina. It is particularly useful in anginal patients with arrhythmias as it has a potent anti-arrhythmic effect at all levels. It can be used in patients with bronchial asthma, in elderly patients and in cardiac failure. However, it may give risk to hypo or hyperthyroidism and so, should not be used in patients with a history or thyroid disorders. Perhexiline has been used in France since 1973 and is a second-line drug to be used in cases of intolerance or contraindications to other anti-anginal drugs. It is effective but may cause severe, undesirable hepatic and neurological complications. These side effects are however rare at low doses. Molsidomine, a more recent molecule, has an action similar to that of the nitrate derivatives: it mainly reduces left ventricular preload. It has a slower onset of action than the classical nitrate derivatives but its duration of action seems to be longer; Molsidomine and betablockade can be a useful therapeutic association.
 ...
PMID:[The classic anti-anginal agents and molsidomine]. 640 52

Molsidomine, one of the sydnonimine group of drugs; the object of this study was to evaluate its efforts in refractory cardiac failure. In the first part of the study, the haemodynamic effects of a single oral dose of 2 or 4 mg of molsidomine were compared with placebo controls in 23 patients. This showed molsidomine to be an active venous vasodilator reducing pulmonary artery and right atrial pressures without changing cardiac index or systemic pressures. The peak effect was observed after 1 to 1,5 hours. In the second phase, molsidomine was used in 9 patients aged 32 to 71 years (mean 47 +/- 12 years) over an average period of 19 months (3,5 to 42 months). The maintenance dose varied from 8 to 24 mg/24 hours. These patients had refractory cardiac failure secondary to primary cardiomyopathy with dilatation (6 cases) or ischemic heart disease (3 cases). The 9 patients were in functional classes IV (5 cases) or III (4 cases). Four patients were theoretically good indications for transplantation. Haemodynamic control was performed 1,8 +/- 5 months after a washout period of 8 hours, and after initial right heart catheterisation, the measurements were repeated 1 hour after oral administration of a 4 mg dose of molsidomine. Two patients did not respond initially to molsidomine; one died, the other remained in functional Class III. Another patient who responded initially was improved for over two years but died in cardiac failure after 42 months' treatment. The other six patients have been significantly improved and were in functional Class II at their last control.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Long-term clinical and hemodynamic results of the treatment of refractory cardiac failure with molsidomine]. 642 98

The aim of the study was to estimate the influence of long-term treatment with molsidomine on structure, systolic function and neurohormonal parameters in patients with chronic heart failure (CHF). Investigations were carried out in 30 patients (mean age 63.0 +/- 10.9) in NYHA class III and IV. The cause of CHF was: coronary artery disease in 60% of patients, hypertension in 20% and dilated cardiomyopathy in 20% of patients. Molsidomine was administrated in dose of 2 mg tid for 3 months. During the study the previous treatment with ACEI, diuretics and digitalis was maintained. Using echocardiographic method left atrial dimension (LA), left ventricular end diastolic (LVEDD) and end systolic diameter (LVESD), interventricular septum (IVSDD) and posterior wall end diastolic diameter (LVPWDD), ejection fraction (LVEF) and fraction of shortening (LVFS) were measured. Plasma level of atrial natriuretic peptide, endotelin, neuropeptide Y and aldosterone and plasma renin activity were estimated radioimmunologically. All echocardiographic and neurohormonal measures were performed 4 times: before therapy, after 3 days, 2 weeks and 3 months of treatment with molsidomine. We observed significant increase in LVEF, which at baseline was 33.8% and after 3 months 44.8% (p < 0.05). None of the other echocardiographic parameters nor any of neurohormonal factors changed significantly during the 3-months treatment with molsidomine.
 ...
PMID:[The influence of 3-month treatment with molsidomine on structure, function and some neurohormonal parameters in patients with chronic heart failure treated with digoxin, diuretic and angiotensin converting enzyme inhibitors]. 977 Oct 14

Molsidomine, coronary drug which acts similar to organic nitrates, belongs to the drug class of sydnones . SIN-1A metabolite of Molsidomine has pharmacologically active group of NO, which by increasing levels of cGMP, decreases levels of intracellular calcium ions in smooth muscle cells. This effect leads to relaxation of smooth muscle vasculature, inhibits platelets aggregation and has indirect antiproliferative effect. In clinical observations no effect of tolerance to the drug was observed. Experimental data show additional mechanism of action of the drug: SIN-1C metabolites protects the reoxygenated cardiomyocyte from post-reperfusion damage. Indications for use of Molsidomine are: ischaemic heart disease, chronic heart failure and pulmonary hypertension. Effects of Molsidomine use in acute myocardial infarction and unstable angina were compared in clinical trials to effects of nitroglycerin use. Both drugs were found equally potent, but authors underline the fact of better Molsidomine tolerability comparing NTG, but longer serum half-time of Molsidomin effects that control of the treatment is worse. In clinical trials it was suggested that intravenous use of Molsidomine metabolite SIN-1 during PTCA procedures is more effective than use of isosorbide dinitrate in the same procedures. In other clinical trials molsidomin was found to produce beneficial effects in patients with heart failure due to ischaemic cardiomyopathy, dilatative cardiomyopathy, in essential hypertension, pulmonary artery hypertension in COPD patients and in congestive heart failure.
 ...
PMID:[Molsidomine: importance in treatment of circulation disorders]. 1022 68

Chronic anthracycline (ANT) cardiotoxicity is a serious complication of cancer chemotherapy. Molsidomine, a NO-releasing drug, has been found cardioprotective in different models of I/R injury and recently in acute high-dose ANT cardiotoxicity. Hence, we examined whether its cardioprotective effects are translatable to chronic ANT cardiotoxicity settings without induction of nitrosative stress and interference with antiproliferative action of ANTs. The effects of molsidomine (0.025 and 0.5mg/kg, i.v.) were studied on the well-established model of chronic ANT cardiotoxicity in rabbits (daunorubicin/DAU/3mg/kg/week for 10 weeks). Molsidomine was unable to significantly attenuate mortality, development of heart failure and morphological damage induced by DAU. Molsidomine did not alter DAU-induced myocardial lipoperoxidation, MnSOD down-regulation, up-regulation of HO-1, IL-6, and molecular markers of cardiac remodeling. Although molsidomine increased 3-nitrotyrosine in the myocardium, this event had no impact on cardiotoxicity development. Using H9c2 myoblasts and isolated cardiomyocytes, it was found that SIN-1 (an active metabolite of molsidomine) induces significant protection against ANT toxicity, but only at high concentrations. In leukemic HL-60 cells, SIN-1 initially augmented ANT cytotoxicity (in low and clinically achievable concentrations), but it protected these cells against ANT in the high concentrations. UHPLC-MS/MS investigation demonstrated that the loss of ANT cytotoxicity after co-incubation of the cells in vitro with high concentrations of SIN-1 is caused by unexpected chemical depletion of DAU molecule. The present study demonstrates that cardioprotective effects of molsidomine are not translatable to clinically relevant chronic form of ANT cardiotoxicity. The augmentation of antineoplastic effects of ANT in low (nM) concentrations may deserve further study.
 ...
PMID:Are cardioprotective effects of NO-releasing drug molsidomine translatable to chronic anthracycline cardiotoxicity settings? 2781 93


1