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)

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

Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide which also has important growth promoting effects on other cellular elements of the vascular wall. Increased local expression and release of endothelin-1 may therefore contribute to abnormal vascular tone and structure in paracrine fashion. Evidence of increased pulmonary production of endothelin-1 by the lung in patients with primary pulmonary hypertension is reviewed, including increased release across the pulmonary circulation and increased vascular expression of the peptide and its mRNA. However, circulating endothelin-1 might also have a humoral action on distant vascular beds. Changes in plasma endothelin-1 in response to postural change and chronic heart failure support a role for this potent vasoconstrictor factor in the neurohumoral response to haemodynamic stress. Thus, like other vascular regulatory mechanisms, the endothelin system might play a dual role in the control of vascular function with both local tissue and circulatory components.
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PMID:Endothelin in cardiopulmonary disease: factor paracrine vs neurohumoral. 790 41

The authors describe a case of primary pulmonary hypertension from the onset of subjective complaints to terminal dextrolateral cardiac failure. They give an account of an unsuccessful attempt to influence the haemodynamics in this female patient by calcium channel blockers. In the discussion they deal briefly with contemporary knowledge and treatment of primary pulmonary hypertension.
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PMID:[Primary pulmonary hypertension]. 821 16

Recent studies have shown that intracellular Ca2+ handling is abnormal in the myocardium of patients with end-stage heart failure. Muscles from the failing hearts showed a prolonged Ca2+ transient and a diminished capacity to restore a low resting Ca2+ level during diastole. Accordingly, we examined whether this defect in Ca2+ transport function is due to alterations in sarcoplasmic reticulum gene expression. We determined the messenger RNA (mRNA) levels of sarcoplasmic reticulum Ca2+ transport proteins in failing human hearts from 17 cardiac transplant recipients with a diagnosis of dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The expression levels of each mRNA were compared with each other and then correlated with that of atrial natriuretic factor (ANF) mRNA in the failing ventricle. The mRNA levels for the calcium release channel (ryanodine receptor, RYR2), Ca2+ uptake pump (Ca(2+)-ATPase, SERCA2 isoform), and phospholamban differed significantly between heart samples but showed an inverse relation with that of ventricular ANF mRNA. In contrast, calsequestrin mRNA levels remained unchanged in these failing hearts. In addition, beta-myosin and alpha-cardiac actin mRNA levels also showed an inverse relation with ANF mRNA levels. These changes were observed in both right and left ventricles of hearts with congestive heart failure due to dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The results are consistent with the hypothesis that abnormal calcium handling in the sarcoplasmic reticulum of failing hearts is due to the altered expression of the genes encoding sarcoplasmic reticulum proteins.
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PMID:Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. 841 95

Nocturnal hypoxemia in daytime normoxemic patients with COPD may lead to an increased right ventricular afterload due to pulmonary hypertension. We investigated the frequency of clinical, electrocardiographical, and radiological signs of right cardiac insufficiency (SRCI) in 178 consecutive COPD-patients [71 bronchitis, 25 emphysema, 82 bronchitis plus emphysema; PaO2 = 60 mm Hg]. Patients with asthma, left ventricular impairment, obstructive sleep apnea syndrome, primary pulmonary hypertension, and neuromuscular diseases were excluded. Polysomnography was performed in all patients. They were divided into 3 groups concerning SRCI: missing, doubtful, and secure SRCI. Parameters of nocturnal pulse oximetry were analyzed within the three groups (Student's t-Test. Chi2-Test. p < 0.05). 25.8% of the patients had secure SRCI without a significant frequency difference between patients with bronchitis and/or emphysema. Patients with secure SRCI had a significant lower mean nocturnal SaO2 than those with missing SRCI (92.7 +/- 2.5 vs. 90.3 +/- 3.5%). With regard to the high prevalence of SRCI in association with nocturnal hypoxemia routine control of nocturnal oxygenation is recommended in daytime normoxemic COPD-patients for the early decision for nocturnal oxygen therapy.
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PMID:[Signs of right heart stress in diurnal normoxemic patients with chronic obstructive lung disease and nocturnal hypoxemia]. 901 80

Endothelins are ubiquitously produced 21-amino-acid peptides that were discovered as an endothelial product and may play important roles in cardiovescular physiology and pathophysiology. The main endothelin produced by the endothelium is endothelin-1. The vasoconstrictor role of endothelins may participate in blood pressure elevation and vascular hypertrophy in salt-dependent models of hypertension (deoxycorticosterone acetate-salt hypertensive rats, spontaneously hypertensive rats treated with deoxycorticosterone, acetate and salt, and Dehl salt-sensitive rats), and in stroke-prone spontaneously hypertensive rats. In humans, endothelins may play important roles in moderate to severe essential hypertension, and in the hypertension of African-Americans. Endothelins may be involved in cardiac hypertrophy, and there is increasing evidence of their participation in heart failure, in which acute endothelin antagonism in humans exerts beneficial effects. Endothelin expression is enhanced in smooth muscle cells migrating into the intima of arteries in atherosclerosis, suggesting a role in atherogenesis. Endothelin may participate as a vasoconstrictor in coronary artery disease, and as a contributor to intimal proliferation in restenosis after coronary angioplasty. In patients with myocardial infarction, cardiac production of endothelin is increased, particularly in those with cardiogenic shock. There is a potential for participation of endothelins in vasospasm accompanying stroke or subarachnoid hemorrhage: in the latter, endothelin antagonism has shown beneficial effects in experimental models. In neonatal and in primary pulmonary hypertension, endothelin expression is enhanced, and in experimental models endothelin antagonism resulted in favorable responses. Systemic sclerosis is another, peripheral, form of vascular disease in which endothelin may play a role and in which endothelin antagonism may be an interesting therapeutic alternative. The pathophysiologic role of endothelins is becoming increasingly apparent in cardiovascular disease, generating interesting potential therapeutic targets for the use of endothelin antagonists or endothelin-converting enzyme inhibitors.
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PMID:Clinical significance of endothelin in cardiovascular disease. 926 47

Blade atrial septostomy (BAS) for pulmonary hypertension has increased long-term survival and is an effective and palliative preliminary to heart and/or lung transplantation. We treated an 18-year-old woman with severe pulmonary primary hypertension whose symptoms had worsened as a resulted low cardiac output. The patient's right ventricular pressure was 150/23 mmHg, cardiac index (CI) 1.0 L/min per m2, and she showed signs and symptoms of severe primary pulmonary hypertension. We performed BAS successfully, paying particular attention to the following points. To maintain pulmonary blood flow after creating an atrial right-to-left shunt, the patient was infused intravenously with packed red blood cells and volume expander. Oxygen delivery was also increased by the transfusion of packed red blood cells. To avoid unacceptable hypoxemia immediately after the procedure, the atrial septum was initially incised with a very small-blade catheter. Nine months after the BAS, catheterization revealed a decrease in mean pulmonary arterial pressure to 73 mmHg and an increase in CI to 2.5 L/min per m2. Thirteen months after the BAS, the patient died as a result of progressive worsening of right-sided heart failure. We concluded that BAS could be successful in patients with severe pulmonary hypertension providing attention is paid to the patient's condition and that BAS is an effective therapy for prolonging survival.
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PMID:Successful blade atrial septostomy in a patient with severe primary pulmonary hypertension--a case report. 938 71

Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction.
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PMID:Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium. 941 Sep 10

We have reviewed the cardiovascular actions of calcioantagonists. These drugs act through L and T channels, inhibiting calcium ions entry at the alpha 1 subunit. The union sites for dihydropiridines (DHPs) are surfacely located (N site) compared to those of diltiazem and verapamil (D and V sites). The administration of calcioantagonists induces peripheral vasodilation with decrease of blood pressure and peripheral resistance; they also act on myocardium inhibiting AV conduction and cardiac contractility. DHPs act more specifically on vascular smooth muscle than myocardium; however, no DHPs (diltiazem and verapamil) act more specifically on myocardium than peripheral vessels. Among drugs of first generation we can mention: nifedipine, diltiazem and verapamil. Among drugs of second generation we have: lacidipine and amlodipine with better tissue selectivity and longer biological half-lives. A recently introduced compound, mibefradil, acts selectively on T channels. The use of calcioantagonists is wide: coronary disease, hypertension, cardiac arrhythmias, ischemic cerebrovascular disease, cardiac failure, primary pulmonary hypertension. World Health Organization has recommended calcium antagonists as first line drugs in hypertension as done with other compounds: diuretics, betablockers, and converting enzyme inhibitors. Recent controversial studies on calcioantogonists should be assessed adequately in order to take a definitive decision.
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PMID:[Role of calcium antagonists in the treatment of arterial hypertension]. 947 Dec 33

Long-term administration of prostacyclin (PGI2) improves the hemodynamic state, symptoms, and survival in patients with primary pulmonary hypertension, but it increases mortality in patients with heart failure despite obvious hemodynamic benefits when it is given acutely. We evaluated the mechanisms of action of PGI2 in patients with heart failure and secondary pulmonary hypertension. Nineteen patients with end-stage heart failure and pulmonary hypertension, all candidates for heart transplantation, underwent right- and left sided cardiac catheterization with micromanometer-tipped catheters and were tested for PGI2 at incremental doses. PGI2 infusion significantly improved pulmonary hemodynamics with a 47% reduction in pulmonary vascular resistance (p=0.0003) and a doubling of pulmonary artery compliance (p <0.0001), reflecting improvement in pulmonary vascular tone. The dose of PGI2 necessary to reach this hemodynamic effect correlated significantly to the baseline severity of pulmonary artery compliance (r=0.54, p=0.01). Furthermore, PGI2 produced a significant positive inotropic effect (contractile element maximum velocity increased from 1.10+/-0.09 to 1.33+/-0.13 circ/s, p <0.009). The hemodynamic effects of PGI2 infusion were independent of the plasma and urinary levels of endogen prostaglandins. Thus, PGI2 at therapeutic doses exerts a positive inotropic effect in patients with heart failure, which may explain the increased mortality rate observed with the long-term use of PGI2 in this type of patient. The spectacular acute benefits on right ventricular afterload, however, may be useful in unstable patients with heart failure and secondary pulmonary hypertension or in transplanted patients with acute right ventricular failure of the donor heart.
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PMID:Effects of prostacyclin on the pulmonary vascular tone and cardiac contractility of patients with pulmonary hypertension secondary to end-stage heart failure. 976 Oct 85


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