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)

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

Vasoconstrictory and vasodilatory hormone systems may be important in the regulation of peripheral vascular resistance and renal hemodynamics in the early phase of heart failure. The activity of the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous activity, and, as possible counterregulating systems, the activity of prostacyclin and atrial natriuretic peptide (ANP) were studied in 6 conscious dogs during the first 4 days of congestive heart failure in relation to hemodynamic changes and renal plasma flow. Congestive heart failure was induced by rapid right ventricular pacing, which caused a considerable decrease of cardiac output (-38%; p less than 0.05), oxygen saturation of the mixed venous blood (-13%; p less than 0.05), and mean arterial pressure (-24 mm Hg; p less than 0.05) on the 4th day. Mean pulmonary arterial pressure and mean pulmonary capillary wedge pressure increased (+4 mm Hg; p less than 0.05 and +7 mm Hg, respectively; p less than 0.05). Renal plasma flow was slightly reduced (N.S.), renal vascular resistance did not change. Peripheral vascular resistance showed a significant increase only on the 1st day. Sympathetic nervous activity was stimulated (from 175 +/- 31 pg/ml to 391 +/- 100 pg/ml; p less than 0.05), while plasma renin concentration was significantly suppressed on the 4th day (from 3.3 +/- 0.4 ngAI/ml/h to 1.9 +/- 0.5 ngAI/ml/h; p less than 0.05), and plasma aldosterone levels were decreased (from 108 +/- 12 pg/ml to 76 +/- 12 pg/ml; p less than 0.05). ANP increased 3-fold (p less than 0.05) and 6-keto-prostaglandin F1 alpha increased in 4 out of 6 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic changes and renal plasma flow in early heart failure: implications for renin, aldosterone, norepinephrine, atrial natriuretic peptide and prostacyclin. 295 80

There is little, if any, good evidence in the literature to indicate a role for cardiovascular PG in congestive heart failure, either in its pathogenesis or as a consequence of and defense against its manifestations. Usually congestive heart failure is considered to develop as a vicious cycle in which impaired cardiac output, increased peripheral resistance, decreased renal blood flow, increased renin release and further increased peripheral resistance and decreased cardiac output are important constituents. Increased sympathetic activity may promote cardiovascular PG formation through the sympathetic neurotransmitter noradrenaline; such an action has, however, not been documented hitherto. Furthermore, increased plasma renin activity may promote PG formation via increased circulating levels of angiotensin; even such an action remains, however, to be demonstrated. If the heart failure leads to local tissue ischemia the hypoxia as such, or the subsequent increase in adenosine production, may also facilitate cardiovascular PG formation. All these mechanisms, if operative, would counteract the increased peripheral resistance, by promoting the formation of vasodilator PG. On the other hand PGI2 stimulates renal formation of renin, which would act to elevate the peripheral resistance. These contradictory effects of endogenously formed PG focus on the need for more careful studies on their involvement in the hemodynamic consequences of congestive heart failure: until more data are available it is impossible to know whether an activated synthesis of PG should be regarded as advantageous and worth therapeutical support, or negative and subject to inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular prostaglandins: some comments on their involvement in circulatory physiology and pathophysiology. 352 21

Mechanically and chemically sensitive receptors in the ventricle have been described histologically and electrophysiologically. Early experiments documented the hypotension and bradycardia that resulted from the intracoronary administration of one of the veratrum alkaloids (the Bezold-Jarisch reflex). Mechanical distension of the ventricles also results in a reflex decrease in heart rate and a reduction in peripheral resistance. Skeletal muscle and coronary vascular resistance appear to be most prominently affected by stimulation of ventricular receptors. Coronary ischemia has also been shown to evoke reflex effects which are attributable to stimulation of ventricular receptors. The resultant bradycardia can be especially ominous in acute myocardial infarction. Changes in myocardial inotropic state have been shown to alter ventricular receptor discharge in experimental animals. This stimulus may evoke reflex changes in peripheral hemodynamics. A variety of humoral substances can alter ventricular receptor discharge and evoke Bezold-Jarisch like responses. These include bradykinin and prostaglandins. PGI2, when given intracoronary in small doses or intravenously in larger doses will lower blood pressure while inhibiting the baroreflex induced tachycardia. It has also been shown in some experiments that PGI2 and arachidonic acid can evoke overt bradycardia and hypotension via a reflex mechanism. The role of prostaglandins in cardiovascular reflex control may be important in pathophysiologic states such as coronary ischemia and heart failure. Ventricular receptors can interact centrally with the arterial baroreceptors to attenuate the baroreflex control of both heart rate and peripheral resistance. Finally, the stimulation of ventricular receptors can alter a variety of humoral substances which are important regulators of cardiovascular and fluid volume homeostasis. These include vasopressin, renin and catecholamines. Those studies which have been done within the last 10 years or so, especially in unanesthetized animals, have demonstrated that the Bezold-Jarisch reflex is more important to cardiovascular control than previously thought. Future work will be necessary to determine the precise role ventricular receptors play in various pathological situations.
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PMID:Left ventricular receptors: physiological controllers or pathological curiosities? 354 77

Vasodilators have been widely used in recent years for the treatment of severe left ventricular failure (LVF). However, amongst these drugs, not all have the same therapeutic effects, but they differ from one another in molecular structures, cellular mechanisms, haemodynamic actions and modes of administration. A three tier classification is proposed with the single objective of facilitating the therapeutic choice: mechanism of action: this property distinguishes the alpha-blockers from the beta-2 sympathomimetics, calcium antagonists, angiotensin converting enzyme inhibitors and prostacyclin biosynthesis inducers. Some molecules such as hydralazine, whose mechanism of action remains unclear, cannot be classified in this way; haemodynamic effects: these effects can be used to distinguish vasodilators which act mainly on the venous sector from arterial and mixed vasodilators. The knowledge of the preferential site ol action of these molecules helps to adapt the choice of treatment to the initial haemodynamic profile of each patient; pharmacokinetics: these properties distinguish molecules active only by intravenous administration, better adapted for the treatment of acute LVF in the intensive care unit, from those active orally which can be used for long-term ambulatory therapy of chronic cardiac failure. Trinitrin and its derivatives occupy an intermediate position because of their relatively low bioavailability after oral administration: long-term administration is not always easy and may require special modes of administration (i.e. percutaneous). Vasodilators have been widely used in cardiac failure for about 5 years; the results of some medium term controlled therapeutic trials are now available and confirm the efficacy of these drugs but also define their limitations: variable therapeutic efficacy: the number of responders ranges from 30 to 60 p. 100 according to the molecule used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Classification and principles of the use of vasodilators in the treatment of left ventricular insufficiency]. 392 8

Hemodynamic effects of vasodilator agents (molsidomine, nitroglycerin, isosorbide dinitrate or prostaglandin I2) were studied in 53 patients with acute myocardial infarction. In 20 of these patients, effect on cardiac metabolism were also studied. Patients were divided into four groups according to the Forrester subset and hemodynamic effects of these agents were evaluated by the cardiac index (CI)-preload (PAEDP) relationship. In patients of Forrester subset II and IV, vasodilators were capable of producing a considerable reduction in preload without a significant decrease in cardiac output. However, in patients of Forrester subset IV, five of six patients had only a minimal improvement in cardiac performance with vasodilator therapy because of a severe pump failure. In these patients, a combination therapy with dopamine was necessary to maintain the cardiac output. In patients with Forrester subset III, vasodilator therapy decreased cardiac index and preload was also reduced. Thus, for these patients vasodilators could not be indicated but volume infusion may be indicated. In patients with Forrester subset I, although vasodilator therapy decreased cardiac output, coronary sinus flow and myocardial oxygen consumption were also decreased, indicating that the vasodilator therapy is also beneficial for patients even without heart failure because of the protective effect of unloading on ischemic myocardium. Three nitrate agents, i.e., molsidomine, nitroglycerin and isosorbide dinitrate, demonstrated the similar effect on hemodynamics; mean blood pressure and PAEDP decreased by 7-10% and 20-29%, respectively, while systemic vascular resistance was not significantly decreased. In contrast to nitrates, PGI2 decreased mean blood pressure and systemic vascular resistance significantly, whereas a decrease in PAEDP was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic and metabolic effects of vasodilator therapy for heart failure in acute myocardial infarction. 642 27

Intraarterial or intravenous infusion of prostacyclin at doses 2, 5, and 10 ng/kg/min into 5 subjects without evidence of coronary heart disease or cardiac failure led to marked fall in peripheral, total pulmonary, and capillary wedge resistances. This was accompanied by a moderate drop in intraarterial blood pressure and the acceleration of heart rate leading to compensatory increase in cardiac output. Both stroke volume and mean right atrial pressure remained unchanged. No side effects occurred. Prostacyclin appears to act predominantly on resistance vessels. The hemodynamic effects produced by prostacyclin in man might be of clinical interest in treatment of conditions associated with significant rise in vascular resistance, heart failure, and in limitation of infarct zone during the early stage of acute myocardial necrosis.
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PMID:Hemodynamic effects of prostacyclin in man. 698 3

Intra-arterial or intravenous infusion of prostacyclin at three dose levels (2, 5, and 10 ng/kg per min) in 10 subjects without evidence of coronary heart disease or cardiac failure, led to a distinct fall in peripheral and total pulmonary vascular resistances. This was accompanied by a drop in intra-arterial blood pressure, and the acceleration of heart rate. Stroke volume, cardiac output, mean right atrial pressure, and left ventricular end-diastolic pressure showed no significant changes. Except for sporadic headache no side effects occurred. Prostacyclin appears to act predominantly on resistance vessels. The haemodynamic effects produced by prostacyclin in man might be of clinical interest in the treatment of conditions associated with a significant rise in vascular resistance.
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PMID:Haemodynamic changes induced by prostacyclin in man. 700 Jan 1

Renal prostaglandins play a role in the control of renin release during chronic sodium depletion, during the acute phase of renovascular hypertension and in experimental low output heart failure in conscious dogs. However, with marked inhibition of the renin-angiotensin system, the adrenergic nervous system and the renal prostaglandins, PRA was still 17 times normal during chronic sodium depletion. After blockade of the adrenergic nervous system and the renal prostaglandins, PRA was 10 times normal during the acute phase of one-kidney renovascular hypertension. These findings demonstrate that other important mechanisms, possibly both the renal vascular receptor (so-called baroreceptor) and the macula densa, were involved. Both PGI2 and PGD2 given intrarenally increased renin release in both filtering and nonfiltering kidneys, but PGI2 was more potent than PGD2. Available evidence favors a role of PGI2 and it seems likely that the site of action is on the JG cells. Indomethacin produced a profound drop in CCr and CPAH during sodium depletion and in experimental heart failure which demonstrates an important role for the renal prostaglandins in the control of renal arteriolar tone. An important incidental finding is that renal denervation combined with propranolol administration decreased PRA from very high levels to normal in 50% of the dogs with experimental low output heart failure and a concurrent striking natriuresis occurred.
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PMID:Renal prostaglandins, renin release, and renal hemodynamic function in high renin states. 700 Apr 61

Mild (not harmful) stress may initiate an adaptive mechanism, protecting the heart from harmful consequences of a more severe stress. There are at least three known types of cardiac adaptation to stress, such as: a) the gradually developing, long lasting adaptation to chronic mechanical overload, leading to cardiac hypertrophy, later to cardiomyopathy and heart failure, b) the rapidly developing adaptation to moderate stress initiated by 'preconditioning' brief coronary occlusion(s) or brief periods of rapid cardiac pacing, protecting for less than 1 h against consequences of a subsequent, severe stress, c) the later appearing, more prolonged cardio-protective adaptation, described by us in 1983, induced by various forms of more severe but not injurious stimuli, such as an optimal dose of prostacyclin or its stable analogues; or a series of brief periods of rapid pacings. This form of cardiac adaptation to stress protects for 24-48 h against consequences of a more severe stress such as: 1. myocardial ischaemia; 2. early and late postocclusion and reperfusion arrhythmias; 3. early morphologic changes secondary to ischaemia and reperfusion; 4. ischaemia induced myocardial loss of K+ and accumulation of Na+ and Ca++; 5. it may increase the tolerance to the toxic effects of cardiac glycosides. A reduced response to beta-adrenergic stimuli and a concomitant increase in activity and amount of PDE I and IV was shown by us earlier.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:On the mechanism and possible therapeutic application of delayed adaptation of the heart to stress situations. 749 39


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