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)

Cyclooxygenase inhibitors may affect the hemodynamic status of patients with heart failure adversely and may also block the vasodilatory effects of angiotensin-converting enzyme (ACE) inhibitors in such patients. Relatively low doses of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) are now used routinely in ischemic heart disease, the most important cause of heart failure. Therefore, we investigated the hemodynamic interaction between ASA and captopril in heart failure. In a randomized, cross-over study, 13 patients with congestive heart failure (CHF) who were already receiving maintenance treatment with an ACE inhibitor received a single dose of 25 mg captopril combined with 236 mg ASA or placebo. Peripheral blood flow was studied noninvasively by venous occlusion plethysmography of the calves. Liver blood flow was estimated from indocyanine green (ICG) clearance. Administration of captopril alone significantly decreased blood pressure (BP), and ICG clearance. Calf blood flow remained unchanged. However, after arterial occlusion, hyperemic calf blood flow persisted for longer. Captopril alone did not significantly change the plasma levels of the vasodilating prostaglandins PGI2 and PGE2 or the vasoconstricting thromboxane A2 (TXA2). In contrast, captopril combined with ASA reduced the plasma levels of these vasoactive substances, with significant decreases in PGE2 and TXA2 as compared with captopril alone, yet the hemodynamic alterations after captopril plus ASA were similar to those observed after captopril alone. A single antithrombotic dose of ASA (236 mg) in 13 patients with CHF [New York Heart Association (NYHA) class II-IV] undergoing chronic treatment with ACE inhibitors had no discernible effect on hemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of acetylsalicylic acid on peripheral hemodynamics in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors. 751 53

Endothelins (ET) are a family of peptides with potent biological properties. Endothelial cells produce exclusively ET-1 while other tissues produce ET-2 and ET-3. The production of ET requires an increase in intracellular Ca2+. This increase can be induced by physical chemicals (i.e. hypoxia) or receptor-operated stimuli (i.e. thrombin, angiotensin II, arginine vasopressin, transforming growth factor beta 1, interleukin-1). Most of ET is released abluminally towards vascular smooth muscle and less luminally. The main vascular effect of ET are vasodilation (transient), profound and sustained vasoconstriction as well as proliferation of vascular smooth muscle. These biological effects are mediated by distinct receptors. Three ET receptors have been cloned, i.e. ETA-, ETB- and ETC-receptors. In vascular tissue ETA-receptors are expressed on vascular smooth muscle and responsible for vasoconstriction. ETB-receptors are expressed on endothelium and linked to nitric oxide and/or prostacyclin release. Activation of these receptors explains the transient vasodilation with intraluminal application of ET. Vascular smooth muscle cells can express ETB-receptors which contribute to ET-induced vasoconstriction particularly at lower concentrations. The role of the recently cloned ETC-receptor in the vasculature is still uncertain. ET production is increased (as judged from circulating plasma levels) in vascular disease and atherosclerosis in particular, in myocardial infarction and heart failure, pulmonary hypertension and renal disease. ET production is increased in arterial hypertension remains controversial. Non-peptidic ET antagonists have been developed which either block ETA- receptors or ETA- and ETB-receptors simultaneously. The advantage of ETA-receptors is that they leave the endothelium-dependent vasodilation to ET (via ETB-receptor) intact. However, ETB-mediated contraction remains unaffected by these antagonists. In contrast ETA-/ETB-antagonists fully prevent ET-induced vasoconstriction, however, they also inhibit the endothelial effects of the peptide. ET antagonists interfere with the effects of ET in isolated vascular tissue (including that obtained from humans) as well as in vivo. In humans, ETA as well as ETA-/ETB-antagonists inhibit endothelin-induced vasoconstriction. Hence in summary ET are a family of potent peptides with profound effects in the vasculature. Several studies suggest a role of ET in cardiovascular disease. The newly developed ET-antagonists are potent and selective tools to delineate the (patho-)physiological roles of ET and may become a new class of cardiovascular drugs.
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PMID:Endothelin and endothelin antagonists: pharmacology and clinical implications. 771 86

This multicenter, open-label study provides the first assessment of the safety and acute hemodynamic effects of a short-term infusion of 15AU81, a chemically stable analog of prostacyclin, in patients with New York Heart Association class III or IV heart failure. Twelve patients underwent sequential dose escalation by increasing the rate of the infusion at 15-minute intervals until the drug was no longer tolerated. Patients then received a 90-minute infusion at their maximum tolerated dose. The infusion was then discontinued and the subjects were observed during a 90-minute washout segment. Serial hemodynamic measurements were made throughout the dose-ranging, maintenance, and washout segments. A significant decrease in systemic vascular resistance (1,935 +/- 774 vs 1,243 +/- 351 dynes.s.cm-5; p < 0.001) and pulmonary vascular resistance (395 +/- 335 vs 223 +/- 198 dynes.s.cm-5; p = 0.008) occurred from the infusion of vehicle to the maximum tolerated dose. During dose titration, there was a a significant increase in cardiac index (1.9 +/- 0.7 vs 2.6 +/- 0.6 liters/min/m2; p < 0.001) and a tendency for a mild reduction in pulmonary artery wedge pressure (18 +/- 7 vs 17 +/- 6; p = 0.055) for the 8 patients with values on vehicle and maximum tolerated dose. These hemodynamic changes persisted during the maintenance infusion and disappeared rapidly during the washout segment. The most common adverse event to limit dose-ranging was headache, which occurred at a mean maximum tolerated dose of 36 +/- 15 ng/kg/min. Administration of 15AU81 was associated with significant acute hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute hemodynamic effects of the prostacyclin analog 15AU81 in severe congestive heart failure. 784 51

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.
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PMID:Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group. 784 53

Prostacyclin (PGI2, epoprostenol), a pulmonary and systemic vasodilating agent, has recently undergone long-term intravenous administration trials in patients with severe congestive heart failure. As in many other agents that have beneficial acute hemodynamic profiles, its effects on mortality have been disappointing. However, the drug continues to have a role in the short-term management of patients with decompensated heart failure because of its short half-life, lack of medium-term toxicity compared to sodium nitroprusside, and lesser tendency toward development of tolerance than intravenous nitrates. There may also be therapeutic effects other than its influence on central hemodynamics; in particular, inhibition of platelet aggregation and thrombus formation in small vessels may be of value in the long-term management of patients with primary pulmonary hypertension. It is possible that, like other agents such as vesnarinone (OPC-8212), achieving beneficial long-term effects may require identification of an ideal dose range. The most effective therapeutic doses in long-term administration may not correlate with the most effective doses during short-term hemodynamic studies.
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PMID:Is there a role for epoprostenol in the management of heart failure? 784 54

The patient was a 71-year-old man with dyspnea and bilateral leg edema. He was admitted to our hospital with worsening of dyspnea and had received therapy for chronic heart failure in another hospital. On admission, chest X-ray film revealed dilatation of the cardiac silhouette (CTR: 58%). Electrocardiogram showed atrial fibrillation and negative T wave in II, III, and aVF. Cardiac arteriogram showed no organic lesions, but pulmonary hypertension, pulmonary artery pressure of 60/21/34 mmHg, right ventricular pressure of 40/9/20 mmHg were recognized in pulmonary hemodynamics. The diagnosis of chronic pulmonary thromboembolism was made on the basis of pulmonary arteriogram findings and multiple defects of lung perfusion scintigram. After administration of oral PGI2 analogue for one month, lung perfusion scintigram and right cardiac pressure were markedly improved.
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PMID:[A case of pulmonary thromboembolism with pulmonary hypertension with marked improvement by oral PGI2 analogue]. 796 41

After the discovery by Furchgott and colleagues in 1980 that the endothelium plays an obligatory role in acetylcholine-induced vasodilation many investigators have elucidated the role of the endothelium in the regulation of vascular tone. While the sympathetic nervous system serves the organism as a whole, the endothelium appears to act as a local regulator adapting blood flow to local metabolic needs. A variety of endothelium-derived relaxing and contracting factors such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, endothelin and thromboxane A2 play a role in the endothelium-dependent control of vascular tone. Furthermore, nitric oxide inhibits thrombocyte aggregation and adhesion. Many diseases have been reported to be associated with an impaired endothelium-dependent vasodilation which may contribute to an increased susceptibility to vasospasm, decreased inhibition of thrombus formation and an impaired ability to reduce vascular resistance in ischaemic conditions. In hypertension, hypercholesterolaemia and diabetes mellitus this impairment may be interpreted as an early marker of a process that ultimately will lead to atherosclerosis. The impaired endothelium-dependent vasodilation probably contributes to the increased peripheral vascular resistance in hypertension and heart failure. The role of the endothelium does not seem to be restricted to cardiovascular diseases. Several mediators of inflammation stimulate the endothelium to release nitric oxide, suggesting an important role of the endothelium in the haemodynamic sequelae of sepsis.
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PMID:Endothelium and the regulation of vascular tone with emphasis on the role of nitric oxide. Physiology, pathophysiology and clinical implications. 820 3

Cardiac and arterial baroreflex control of the circulation is abnormal in both human and experimental heart failure. Ventricular vagal afferents mediate mechanical and chemical reflexes, which result in bradycardia and hypotension. The aim of the present study was to evaluate the changes that occur in ventricular mechanoreflexes and chemoreflexes in a conscious canine model of chronic heart failure. Dogs were instrumented for the measurement of left ventricular pressure, left atrial pressure, arterial pressure, and heart rate. Vascular occluders were placed on the ascending thoracic aorta, on the descending thoracic aorta, and on the thoracic inferior vena cava. A chronic left circumflex coronary artery catheter was also implanted. Finally, a pacing lead was secured to the left ventricular free wall. After recovery from surgery (10 to 14 days), the dogs were subjected to complete arterial baroreceptor denervation. The responses to vascular occlusions and intracoronary administration of prostacyclin (PGI2) were carried out before and after heart failure was induced by chronic cardiac pacing at 250 beats per minute. PGI2 was used as a chemical stimulus for ventricular afferents; ascending aortic occlusion was used as a mechanical stimulus. Before chronic pacing, ascending aortic occlusion resulted in a decrease in heart rate of 36.1 +/- 12.3 beats per minute (mean +/- SD, P < .001). After heart failure was induced, the heart rate response to ascending aortic occlusion was almost completely abolished. The slope of the linear relation between pulse interval and left ventricular end-diastolic pressure was reduced by 90.5% from a control value of 11.3 +/- 6.9 ms/mm Hg after heart failure had been induced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventricular mechanoreflex and chemoreflex alterations in chronic heart failure. 829 65

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and calcium antagonists are complementary. While ACE inhibitors inhibit the renin-angiotensin system and reduce sympathetic outflow, calcium antagonists dilate large conduit and resistance arteries. Certain calcium antagonists, such as verapamil, lower heart rate. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are also complementary. While ACE inhibitors inhibit activation of angiotensin I into angiotensin II and prevent the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin formation), calcium antagonists inhibit the effects of vasoconstrictor hormones such as angiotensin II at the level of vascular smooth muscle by reducing calcium inflow and facilitating the vasodilator effects of nitric oxide. Calcium antagonists reduce smooth muscle cell proliferation and atherosclerosis. In hypertensive animals, verapamil and trandolapril normalize endothelial dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the development of new atherosclerotic plaques. After myocardial infarction, verapamil reduces mortality and cardiac events in patients without heart failure. In contrast, ACE inhibitors are effective after myocardial infarction in patients with impaired left ventricular function. Urinary albumin excretion rate decreases during ACE inhibitor therapy or with a calcium antagonist such as verapamil; combination of the two drugs has an additive effect. In resistance arteries, hypertension is associated with an increased media/lumen ratio. ACE inhibitors, but not beta-blockers, markedly improve these structural changes. In summary, ACE inhibitors and calcium antagonists have a complementary profile, both in their hemodynamic and local vascular action. Hence, combination therapy with these two classes of drugs appears particularly useful in patients with hypertension, not only to lower blood pressure, but hopefully to achieve improved cardiovascular protection.
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PMID:Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases. 856 68

Endothelin-1 is a recently discovered peptide mainly released from endothelial cells. Hypoxia and ischemia as well as numerous factors such as angiotensin 11, thrombin and transforming growth factor beta 1 stimulate the formation of the peptide. On the other hand the synthesis of endothelin is inhibited by nitric oxide and atrial natriuretic peptide via the formation of cyclic guanosine monophosphate. Released from endothelial cells endothelin-1 mediates transient vasodilation followed by a profound and longlasting vasoconstriction. Endothelin is also a mitogen for smooth muscle proliferation. Endothelins exert their biological effects via activation of specific receptors. Two different receptors have been cloned from mammalian tissues (ET(A) and ET(B) receptors). On vascular smooth muscle cells both receptors mediate contractions. Endothelial cells only express ET(B) receptors linked to the formation of nitric oxide and/or prostacyclin formation. Increased plasma concentrations of endothelin-1 have been described in a variety of diseases such as pulmonary hypertension, arteriosclerosis, renal failure, acute coronary syndromes, heart failure, migraine and vascular diseases. Recently an increasing number of endothelin receptor antagonists have been synthetized, which have been shown to inhibit endothelin-mediated vasoconstriction. Clinical studies are now ongoing to elucidate the pathophysiologic role of endothelin and the potential benefit of the blockade of the system in different disease states.
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PMID:Endothelin and endothelin antagonists: potential role in cardiovascular and renal disease. 873 56


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