Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of dilated cardiomyopathy is primarily concerned with that of congestive heart failure. Digitalis is widely use in dilated cardiomyopathy but an improvement in the prognosis has not yet been demonstrated. Furthermore, the effects of digitalis in patients with sinus rhythm are debatable. If dilated cardiomyopathy induces atrial fibrillation and tachyarrhythmia, digitalis should be used. Diuretics are helpful in the treatment of congestive heart failure associated with dilated cardiomyopathy. By reducing hypervolemia and by venous dilatation, diuretics lower preload and afterload. This leads to relief of congestion and termination of the vicious cycle of congestive heart failure. Accordingly, the prognosis of dilated cardiomyopathy might be improved by diuretics. There are numerous diuretics acting differently on the renal tubules, the choice of which depends on the renal function and serum electrolyte concentrations. Reduction of preload and afterload improves congestive heart failure as has been demonstrated repeatedly. Many substances have therefore been used for arterial and venous dilation with differing results. At least for short-term periods, congestion is reduced and cardiac output increases. Especially inhibitors of angiotensin II converting enzyme are very effective since they act both in the arterial and venous systems. Additionally, inhibition of the action of angiotensin may be regarded as causal therapy since the renin-angiotensin system is the trigger for vasoconstriction and fluid retention in congestive heart failure. Unlike other substances, ACE inhibitors have been demonstrated to improve prognosis of patients with congestive heart failure. At present, combined diuretic therapy and angiotensin conversion enzyme inhibition would seem the most reasonable treatment for patients with dilated cardiomyopathy and sinus rhythm. If atrial fibrillation and tachyarrhythmia develop, additional digitalis therapy is effective.
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PMID:[Therapy of dilated cardiomyopathy with digitalis, diuretics and vasodilators]. 299 Oct 95

An infant of Arab extraction with the Type II form of Gaucher's disease is described. His clinical presentation was unusual because in addition to the extensive neurological involvement and marked hepatosplenomegaly a severe congestive cardiomyopathy and renal tubular dysfunction were present. In addition, marked hypergammaglobulinemia and raised serum angiotensin converting enzyme levels were found. It is suggested that these varied manifestations may be ascribed to the consequences of glucocerebroside deposition within the macrophages of the reticuloendothelial system.
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PMID:The varied clinical and laboratory manifestations of type II Gaucher's disease. 303 64

The authors have compared the short-term effect of two captopril (ACE inhibitor) preparations namely the Lopirin (SQUIBB) and Tensiomin (EGIS) and dihydralazine as well as placebo in 15 patients with severe heart failure (NYHA III-IV, class). In case of 8 patients with NYHA IV, functional class the short-term effect of the combined therapy of dihydralazine and Lopirin and dihydralazine and Tensiomin as well dihydralazine and placebo have been compared. The underlying disease was dilated cardiomyopathy (DCM) and ischaemic heart disease (IHD). At the end of the treatment with different drugs and placebo the clinical signs of heart failure (complaints and physical status) and the echo and mechanocardiographic parameters of left ventricular function were assessed. The parameters, apart from the clinical signs, have been evaluated in double blind fashion. Compared to placebo all the three drugs i.e. dihydralazine, Lopirin as well as Tensiomin have decreased significantly the NYHA classes, influenced favorably the non-invasive parameters of left ventricular function and decreased blood pressure. As to the dihydralazine, it improved the left ventricular ejection function and the clinical state of the patients with DCM in a higher degree than the two ACE inhibitors did. The effect of Tensiomin and Lopirin was the same in every respect. Both have influenced more favourable the complaints and physical state of patients with IHD than dihydralazine has. The left ventricular filling pressure, the double product (heart rate x wall tension) indicating the myocardial oxygen demand were more reduced in their effect than in that of dihydralazine. Unlike dihydralazine both decreased the heart rate. Administering one of the two ACE inhibitors to the dihydralazine beneficial additive effects have been experienced; the NYHA classes, the heart rate, the left ventricular wall tension and the double product diminished. The authors, on the bases of the results, consider Tensiomin and Lopirin as equivalent in their effect. In their opinion the administration of these drugs mean a new, efficient way of therapy, first of all in cases of heart failure caused by IHD. In the most severe cases they suggest a trial with the combined dihydralazine-ACE inhibitor therapy.
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PMID:Comparative study on the short-term effects of angiotensin converting enzyme inhibitors (Lopirin, SQUIBB and Tensiomin), and dihydralazine in chronic cardiac failure. 307 6

This 3-part discussion of captopril, the first oral angiotensin converting enzyme (ACE) inhibitor, focuses on the clinical use and superiority of this agent to standard treatments and the new observations that use can improve the overall poor survival associated with heart failure. Today, as in the past, treatment of CHF includes digoxin and diuretics. Vasodilators have been relegated by some to the role of supplementing therapeutic regimens when patients remain symptomatic. Recently, controlled studies have shown that the introduction and supplementation of therapeutic regimens with ACE inhibitions and specifically captopril is associated with substantial clinical benefits: Symptoms are reduced as hemodynamics and exercise capacity improve, metabolic derangements (including fluid retention, potassium and magnesium loss and sympathetic nervous activation) are reduced with resultant favourable effects on arrhythmia frequency and finally the newest and most dramatic observation of improved survival. This review will briefly summarize these developments and assist in the clinically important aspects of this therapy for practicing physicians. Guidelines for the clinical use of captopril: In patients with confirmed dilated cardiomyopathy, captopril improves stroke volume in response to afterload reduction, but in volume-contracted patients vasodilation may be associated with hypotension. Therefore, prior to initiating captopril, the diuretic dosage should be reduced, particularly in low serum sodium concentration states if intravascular volume is depleted. Potassium supplements should be stopped due to the expected decrease of aldosterone production and improved potassium retention. Initial therapy should be started with a low captopril dosage (2 to 3 times 6.25 mg/day), maintenance dosages are 25 or 50 mg b.i.d. or t.i.d. Superiority to other vasodilator drugs and use in mild cases: In studies of acute and chronic CHF, captopril improves hemodynamics, exercise tolerance, and reduces symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Captopril in the treatment of congestive heart failure. 332 93

Acute hemodynamic effects of oral 25 mg of the angiotensin converting enzyme inhibitor captopril were studied in 8 patients suffering from left ventricular failure and severe chronic obstructive lung disease (COLD) with pulmonary hypertension. In all the patients left ventricular failure resulted from a dilated cardiomyopathy. No significant change in right or left ventricular function and a decrease of 10% in arterial blood pressure and total systemic resistances were observed after administration of captopril. It is suggested that patients suffering from left ventricular failure and severe chronic obstructive lung disease will not benefit from administration of captopril.
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PMID:[Effect of captopril on pulmonary arterial hypertension in congestive heart failure associated with chronic obstructive bronchopneumopathy]. 639 82

In chronic heart failure, the inter-relationship of the renin-angiotensin-aldosterone system (RAAS) and cardiac growth is of primary clinical interest. In the pressure or volume overloaded heart, hypertrophic growth of the myocardium includes the enlargement of cardiac myocytes--an adaptation governed by ventricular loading. Nonmyocyte cell growth involving cardiac fibroblast may also occur but not primarily regulated by the hemodynamic load. Cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium and adventitia of intramyocardial coronary arteries. In addition to relaxation abnormalities due to impairment of sarcoplasmic Ca(2+)-ATPase activity, this remodeling of the cardiac interstitium represents a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness, leading to ventricular diastolic and systolic dysfunction and ultimately the appearance of symptomatic heart failure. In vivo and in vitro studies suggest that the effector hormones, angiotensin II and aldosterone, of the RAAS are primarily involved in regulating the structural remodeling of the myocardial collagen matrix. In cultured adult cardiac fibroblasts, angiotensin II and aldosterone have been shown to stimulate collagen synthesis while angiotensin II additionally inhibits matrix metalloproteinase 1 activity, which is the key enzyme for interstitial collagen degradation in the myocardium. These observations may serve as rationale why angiotensin converting enzyme inhibition or blockade of the RAAS represents such remedial therapy in congestive heart failure in patients with hypertensive heart disease, post-myocardial infarction or with dilated cardiomyopathy.
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PMID:Myocardial collagen matrix remodeling and congestive heart failure. 763 1

The cardiac interstitium is composed of nonmyocyte cells and a structural protein network which plays a dominant role in governing the structure, architecture, and mechanical behavior of the myocardium. The heterogeneity in myocardial structure, created by the altered behavior of nonmyocyte cells, particularly cardiac fibroblasts which are responsible for myocardial collagen metabolism and fibrous tissue accumulation, may largely explain the appearance of diastolic and/or systolic myocardial failure. Regulatory mechanisms that are related to the fibrous tissue response in various cardiovascular diseases, e.g., hypertensive heart disease, dilated cardiomyopathy or post myocardial infarction, are of primary clinical interest. A better understanding of the hitherto neglected role of cardiac fibroblasts in mediating an adverse structural remodeling of the myocardium will lead to specific pharmacologic agents that interfere with the fibrous tissue response. Several lines of evidence based on in vivo and in vitro studies suggest that circulating and tissue renin-angiotensin-aldosterone systems (RAAS) are involved in the structural remodeling of the nonmyocyte compartment, including the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition or aldosterone receptor antagonism that was found to prevent myocardial fibrosis in the rat with renovascular or genetic hypertension. In cultured adult cardiac fibroblasts, an angiotensin (Ang)II- or aldosterone-mediated dose-dependent increase in collagen synthesis could be completely abolished by the use of AngII type 1 or mineralocorticoid receptor antagonists, respectively. Likewise, the AngII-mediated decrease in the activity of matrix metalloproteinase 1, the key enzyme for interstitial collagen degradation, could be antagonized by AngII receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological modulation of cardiac fibroblast function. 777 64

The analysis of currently used therapeutic targets provides considerable input in the choice of current and future therapies for dilated cardiomyopathy and congestive heart failure. Of the ion flux agents, a definitive answer concerning digoxin will soon be available. Currently, digoxin is likely of benefit to patients with persistent heart failure and significantly enlarged hearts despite therapy with preload and afterload reducing agents. Most currently available calcium channel blocking agents do not appear to be effective, although newer agents such as amlodipine and felodipine have yet to be adequately tested. Vesnarinone, which operates through the sodium and potassium rectifying channels and has limited phosphodiesterase inhibition, appears to provide a significant improvement in mortality and in symptoms. Part of the latter effect may be due to its anticytokine properties, which are currently being investigated. Analysis of vascular endothelial agents indicate that not all of the vasoactive agents improve survival, as demonstrated with prazosin and flosequinan. The dose of agents may be important, again demonstrating that less is better. Finally, those with additional effects, such as inositol triphosphate stimulation, may offer additional unique properties that may, in the future, provide benefit. Phosphodiesterase inhibitors are potentially beneficial in the short term but clearly should be avoided for long-term use. Lower doses of these agents are now being investigated, but the weight of evidence is against agents that operate primarily through phosphodiesterase inhibition. Renin angiotensin agents are the most efficacious of therapies available at this time. New angiotensin converting enzyme inhibitors are likely to add little to what is already known.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New medical therapies for advanced left ventricular dysfunction. 779 29

Chronic systolic heart failure after coronary heart disease or dilated cardiomyopathy is characterized by an increasing dilatation of the left ventricle and raised intracardial pressures. The higher the NYHA class, the higher are usually preload and afterload of the left ventricle. Concomitantly, the renin-angiotensin-aldosterone-system is stimulated, leading to neurohormonal activation of vasoconstrictive hormones. This will reduce the already depressed myocardial function even more. The addition of ACE-inhibitors to diuretics and digitalis has improved the prognosis of patients with severe and moderate heart failure. Thus, there is no question today that ACE-inhibitors are needed in chronic heart failure, irrespective of the origin. New investigations indicate that diuretics and digitalis are also needed in severe or moderate heart failure. They certainly lead to a decrease of symptoms. The significance of the local ACE-system seems to be greater than that of the circulating ACE-system, when chronic heart failure after myocardial infarction has to be treated. The prophylactic use of ACE-inhibitors after myocardial infarction with decreased ejection fraction will reduce the necessity of admittance to hospital and will also improve the prognosis.
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PMID:[Indications for ACE inhibitors in chronic heart failure]. 785 85

The therapeutic approach to dilated cardiomyopathy (DCM) still remains nonspecific and symptomatic, since no specific etiology is identified. Nevertheless, the recent introduction of angiotensin converting enzyme (ACE) inhibitors and beta-blockers greatly improved the treatment of DCM. The poor prognosis of patients with DCM encourages maximal aggressive attempts to prevent progression of ventricular dysfunction rather than to wait for treatable symptoms. To achieve this goal, vasodilators, particularly ACE inhibitors, now appear to be essential for the treatment of DCM. Digitalis is added unless contraindicated by adverse effects. Diuretics should be used only to relieve congestive symptoms. In the presence of sinus tachycardia or ventricular arrhythmias, beta-blockers are the next choice in our practice. When congestive symptoms or low output state are not controlled with vasodilators, diuretics, and digitalis, inotropic agents are indicated, with or without mechanical assist devices. For severely ill patients unresponsive to maximal medical management, heart transplantation is needed.
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PMID:Therapeutic management of dilated cardiomyopathy. 791 2


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