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)

Angiotensin converting enzyme inhibitors (ACE-I) are widely used in patients with severe heart failure on the basis of the significant improvement in mortality in the CONSENSUS-I trial in patients with Class IV heart failure. Recent data from the 5-year clinical trial Studies of Left Ventricular Dysfunction (SOLVD) suggest a role for ACE-I in patients with mild to moderate heart failure as well as in those with asymptomatic left ventricular dysfunction. The SOLVD treatment trial in patients with a left ventricular ejection fraction (LVEF) less than or equal to 35% and treated for heart failure with conventional therapy including digitalis, diuretics, or vasodilators demonstrated that the addition of enalapril resulted in a significant reduction in mortality from heart failure as well as in the combined end point of death plus hospitalization from heart failure. These data suggest that ACE-I should be the base of therapy for patients with mild to moderate heart failure, as well as for those with severe heart failure.
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PMID:Congestive heart failure: new therapeutic strategies. 139 11

The intrarenal renin-angiotensin system (RAS) may contribute to the pathophysiology of heart failure by the generation of angiotensin II at local sites within the kidneys. Angiotensin II may directly influence renal hemodynamics, glomerular contractility, and tubular sodium reabsorption, thereby promoting sodium and fluid retention in this syndrome. In the present study, we examined components of the circulating RAS as well as the intrarenal expressions of renin and angiotensinogen mRNA in rats with stable compensated heart failure (HF) 12 wk after experimental myocardial infarction. Renal angiotensinogen mRNA level in vehicle-treated HF rats increased 47%, as compared with sham control rats (P = 0.001). The increase in angiotensinogen mRNA levels was more pronounced in animals with medium (46%, P < 0.05) and large (66%, P < 0.05) infarcts than in those with small infarcts (31%, P = NS). There were no differences in liver angiotensinogen mRNA, circulating angiotensinogen, angiotensin II, plasma renin concentration (PRC), kidney renin content (KRC), and renal renin mRNA level between sham and HFv. In addition, in a separate group of rats with heart failure, we demonstrated that renal angiotensin II concentration increased twofold (P < 0.05) as compared with that of age-matched sham operated controls. A parallel group of heart failure rats (HFe, n = 11) was treated with enalapril (25 mg/kg per d) in drinking water for 6 wk before these measurements. Blood pressure decreased significantly during treatment (91 vs. 103 mm Hg, P < 0.05). Enalapril treatment in HF rats increased renin mRNA level (2.5-fold, P < 0.005), KRC (5.6-fold, P = 0.005), and PRC (15.5-fold, P < 0.005). The increase in renal angiotensinogen mRNA level observed in HFv rats was markedly attenuated in enalapril treated HF rats (P < 0.001), suggesting a positive feedback of angiotensin II on renal angiotensinogen synthesis. These findings demonstrate an activation of intrarenal RAS, but no changes in the circulating counterpart in this model of experimental heart failure, and they support the concept that the intrinsic renal RAS may contribute to the pathophysiology in this syndrome.
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PMID:Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure. 140 Oct 84

Angiotensin converting enzyme inhibitors (ACEI) are used increasingly to treat cardiovascular diseases, and so, therefore, the number of patients scheduled for surgery and treated preoperatively with these drugs. Haemodynamic instability has sometimes been observed during anaesthesia in these patients, leading some authors to discontinue ACEI administration before anaesthesia. However, recent physiological data concerning the renin angiotensin system (RAS) and ACEI pharmacological data may increase our understanding of the mechanisms of cardiovascular interaction between ACEI and anaesthesia. The RAS is involved in blood pressure regulation when extracellular fluid volume is decreased and in case of hypovolaemia, by inducing vasoconstriction and longterm volume regulation. Arterial vasoconstriction is the target for ACEI. However, venoconstriction may maintain venous return and cardiac output in spite of reduced blood volume. On the other hand, ACEI treatment impedes cardiac adaptation to acute changes in extracellular fluid volume. This effect may be increased by underlying pathology (especially in hypertension) as well as by anaesthesia. A combination of an increased sensitivity to acute changes in ventricular load due to treatment with ACEI and anaesthesia in hypertensive patients or in patients with cardiac failure may carry a high risk of hypotension. Specific studies on haemodynamic tolerance of anaesthesia in patients chronically treated with ACEI are required to assess the prevalence of this risk and how to manage it.
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PMID:[Anesthetic consequences of hemodynamic effects of angiotensin converting enzyme inhibitors]. 141 79

Angiotensin converting enzyme inhibitors have greatly improved the treatment of patients with chronic heart failure but they are not effective in all patients, and their use may be limited by side effects. There is, therefore, a need to investigate new drugs and to compare their efficacy with angiotensin converting enzyme inhibitors. Flosequinan is a new direct-acting vasodilator that has been shown to be effective in placebo-controlled studies. Patients with chronic heart failure in NYHA classes II or III who remained symptomatic despite at least 80 mg of frusemide daily were recruited from two centers. Following a single-blind placebo run-in period, the patients were randomized double blind to either the addition of captopril or flosequinan for 6 weeks. Following a further 2-week placebo washout period, they were then given the alternative treatment. Symptom-limited treadmill exercise times, scores of perceived exertion, and corridor walk tests were measured at two weekly intervals during the study. Twenty-five patients entered the study, 16 of whom completed without a change in diuretic dose. Five patients were withdrawn while taking captopril and two while taking flosequinan; two were withdrawn during the placebo washout period. For those patients who completed the study, flosequinan increased treadmill exercise tolerance from a mean (SEM) placebo time of 11.5 (1.0) minutes by 2.4 (0.6) (p = 0.0002) and captopril from 12.0 (0.8) minutes by 1.2 (0.6) minutes (p = 0.08). Comparison of the other measures of efficacy revealed no difference between the groups. In this short-term study flosequinan appeared to be equal in efficacy to captopril.
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PMID:A comparison of the effects of captopril and flosequinan in patients with severe heart failure. 145 90

The prognosis for patients with congestive heart failure (CHF) is poor, with a mortality exceeding 50% within 5 years from diagnosis. This poor prognosis remains despite improved pharmacological therapy. Because the prevalence of sudden death among these patients is high, reported to exceed 40%, the prognostic importance of ventricular tachyarrhythmias has attracted much interest. Long-term electrocardiographic monitoring of patients with CHF reveals a high prevalence of ventricular premature beats, which in many patients occur frequently or are complex according to Lown criteria. Ventricular tachycardia (three or more consecutive beats) has been recorded in 40% or more of the patient population. Whether the occurrence and/or severity of ventricular tachyarrhythmia detected on Holter electrocardiograms relates to the subsequent prognosis is, however, debated. The occurrence of ventricular tachyarrhythmia may just be an expression of severely compromised left ventricular function, which, in turn, decides the subsequent outcome of the disease. Besides myocardial injury, patients with CHF have many factors that may contribute to the high prevalence of ventricular arrhythmias. Among these are elevated levels of plasma norepinephrine. Angiotensin II may increase the sensitivity to sympathetic nervous system arousal but also promotes renal loss of potassium and magnesium. Treatment with digitalis and diuretic drugs may provoke arrhythmias as well. Heart failure therapy may, however, also improve ventricular arrhythmias. Accordingly, it has been demonstrated that captopril therapy significantly reduces ventricular prematurity, compared with digitalis. In contrast, however, enalapril improvement of mortality was due to a reduction of progressive heart failure, with no difference seen in the incidence of sudden cardiac death (the CONSENSUS study).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of congestive heart failure treatment on incidence and prognosis of ventricular tachyarrhythmias. 172 20

The effects of the angiotensin converting enzyme inhibitor captopril, after treatment for 5-6 weeks with 25 mg t.i.d., were studied in 12 patients with stable moderate heart failure. Five patients received placebo treatment, and the two groups were comparable at baseline. Angiotensin II levels decreased in response to captopril therapy. Skeletal muscle potassium, magnesium and chloride levels did not differ from reference values. Calcium was subnormal (P less than 0.0001), but increased to the reference range during captopril treatment. Phosphofructokinase, a rate-limiting glycolytic enzyme, was in the lower reference range and increased (P less than 0.04) in response to captopril therapy. In conclusion, stable moderate heart failure is associated with low levels of skeletal muscle calcium and phosphofructokinase activity, these metabolic changes tending to return to normal levels with captopril treatment.
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PMID:Skeletal muscle depressed calcium and phosphofructokinase in chronic heart failure are upregulated by captopril--a double-blind, placebo-controlled study. 182 3

Angiotensin converting enzyme (ACE) inhibitors are well established in the treatment of hypertension and cardiac failure. Experimental studies in rats have suggested that these agents may protect renal function in chronic nephropathy by a mechanism other than simply lowering the systemic blood pressure. In human studies of incipient diabetic nephropathy, worsening of microalbuminuria was prevented during 3 years of ACE inhibition. ACE inhibitors reduce arterial blood pressure in chronic nephropathy, and may cause a fall in glomerular filtration rate. In diabetic nephropathy, proteinuria was reduced by 2 months' treatment with enalapril to less than half of the values obtained in a control group treated with metoprolol. Nonrandomised trials have suggested that ACE inhibitors may slow the deterioration of renal function, but no comparisons with other antihypertensive agents in prospective studies have been published to date. In chronic renal failure, ACE inhibitors may worsen anaemia and hyperkalaemia. Renovascular hypertension can be treated with ACE inhibitors, but the treatment may lead to a compromised renal function. The dosage of these drugs should be reduced in renal failure and therapy should be started cautiously in this setting, with close monitoring of blood pressure, renal function and plasma potassium.
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PMID:Angiotensin converting enzyme (ACE) inhibitors and renal function. A review of the current status. 193 Jul 42

Angiotensin converting enzyme inhibitor therapy decreases the production of the vasoconstrictive angiotensin II and reduces the degradation of certain kinines of vasodilatator action. Of captopril, enalapril, and lysinopril marketed abroad, only captopril of shorter action is available in Hungary. Angiotensin converting enzyme inhibitors are new means for the therapy of hypertension and congestive heart failure. Captopril seems to be effective at an early stage of heart failure. It slows down or even inhibits the progression of heart failure. New aspects of therapy have been revealed. It may be successfully used in angina pectoris, for the prevention of reperfusion arrhythmias accompanying myocardial infarction, for the treatment of renoparenchimal renal diseases, diabetic nephropathy. The side-effects, interactions, and dosage of angiotensin converting enzyme inhibitors have also been discussed.
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PMID:Angiotensin converting enzyme inhibitor therapy. 194 79

There is activation of the renin angiotensin system after both complicated and uncomplicated myocardial infarction. Angiotensin II increases myocardial oxygen consumption whilst reducing coronary flow and is also directly toxic to the myocardium. Angiotensin converting enzyme inhibitors produce beneficial haemodynamic and neuroendocrine changes in patients with acute left ventricular failure, and may have a role in selected patients with cardiogenic shock. There is evidence to suggest that they might prevent the development of late cardiac failure by limiting the extent of post infarction ventricular dilation. Further research is necessary to define their role in the treatment of acute myocardial infarction.
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PMID:Importance of RAA system and the treatment of patients with ACE inhibition after myocardial infarction. 201 17

Several changes in neuroendocrine activity follow failure of cardiac function to satisfy peripheral requirements and contribute to the clinical syndromes of heart failure. Afferent pathways are poorly understood and triggers are both central and peripheral, involving attenuation of atrial and arterial baroreceptor activity. Efferent sympathetic activity is generally increased with resulting vasoconstriction, but responses are organ-specific and differ among heart, kidney, lung and skeletal muscle. Changes in cardiac sympathetic activity are inadequately understood. Enhanced cardiac norepinephrine spillover contrasts with reduced tissue concentration and impaired activity of synthetic enzymes and neuronal catecholamine uptake. Beta-receptor down-regulation further complicates overall adrenergic responsiveness and the balance between enhancement of contractile function and reduction in arrhythmia threshold. Activation of the renin-angiotensin system is potentiated by the sympathetic nervous system and may contribute to vasoconstrictor hyporesponsiveness. Angiotensin II may in turn facilitate the central and peripheral effects of sympathetic activation and the release of vasopressin from the pituitary. Our understanding of the role of vasodilator peptides in heart failure remains rudimentary. It is likely that vasoconstrictor neuroendocrine response adversely influences optimal cardiac function in heart failure and may promote arrhythmogenesis. The neuroendocrine response in individual organs, however, requires intensive study.
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PMID:Neuroendocrine activation in congestive heart failure. 202 Nov 17


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