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

Coronary artery occlusion results in the acute activation of the renin-angiotensin system and production of angiotensin II, a potent vasoconstrictor and positive inotropic agent. This has raised the possibility that angiotensin converting enzyme (ACE) inhibitors might be "cardioprotective" (that is, might attenuate myocardial injury, dysfunction and necrosis) in the setting of acute ischemia and infarction. Captopril, enalapril and ramipril have, in fact, been reported to acutely limit myocardial injury and necrosis in models of permanent coronary artery occlusion. The mechanisms responsible for this cardioprotection are complex, but include favorable alterations in myocardial oxygen supply/demand, and, in some instances, inhibition of bradykinin metabolism and/or increased prostaglandin synthesis. Other studies, however, have failed to document a reduction in infarct size with ACE inhibitor treatment. Results obtained in models of coronary occlusion/reperfusion have also been mixed. In models of brief transient ischemia not associated with necrosis, captopril and zofenopril have consistently been found to attenuate postischemic contractile dysfunction of the viable but "stunned" myocardium during the early hours following relief of ischemia. In contrast, there is no consensus on the effects of enalapril on the stunned myocardium: both positive and negative results have been obtained. Similar disparity has been reported in models of more prolonged ischemia/reperfusion resulting in subendocardial necrosis: some studies have reported myocardial salvage, while others have provided disturbing evidence of apparent exacerbation of myocardial necrosis with captopril and enalapril therapy. Thus, after a decade of investigative effort, the question of whether ACE inhibitors are "cardioprotective" in the setting of acute myocardial ischemia and infarction remains unresolved. Nonetheless, clinical protocols are in progress to assess the effects of early ACE inhibitor treatment in patients with acute myocardial infarction.
 ...
PMID:"Cardioprotection" by ACE-inhibitors in acute myocardial ischemia and infarction? 835 29

Disturbances of the fibrinolytic system have been associated with cardiovascular disease and its risk factors. In the present study the effects of an ACE-inhibitor (enalapril) and a placebo on the fibrinolytic system have been compared. Eighty one survivors of acute myocardial infarction were randomised to treatment with enalapril or placebo. The mass concentrations and activity of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in plasma were measured three months after the infarction. The enalapril group had a significantly lower level of tPA antigen compared to the placebo-treated group (9.2 and 10.6 respectively). There was no difference between the two groups in any of the other fibrinolytic variables. We conclude that survivors of myocardial infarction treated with enalapril have a significantly lower concentration of tPA antigen than those treated with placebo. This may have a prognostic implication, as lower plasma concentrations of tPA antigen have been associated with better prognosis in patients with established coronary heart disease.
 ...
PMID:Enalapril related changes in the fibrinolytic system in survivors of myocardial infarction. 835 88

Plasma neurohormones were sequentially analysed in 98 patients with acute myocardial infarction randomized to treatment with enalapril or placebo for 4-6 months. Plasma angiotensin converting enzyme activity was rapidly suppressed by enalapril, but unaffected by placebo (P = 0.0001). No significant differences were found in the plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide, noradrenaline, adrenaline or dopamine between the two treatment groups. Among patients with infarct size above median, plasma angiotensin II increased during head-up tilt at one month in the placebo group, but not in the enalapril group. Left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were evaluated by echocardiography in 28 patients (placebo 15, enalapril 13) and changes in left ventricular volumes between baseline and 4-6 months were calculated. Only in the placebo group was a positive correlation found between plasma levels of noradrenaline at day 5-7 and the subsequent increase in LVEDV (r = 0.78, P = 0.005) and LVESV (r = 0.75, P = 0.008). The same trend was found for angiotensin II, adrenaline and dopamine levels at days 5-7 and the subsequent increase in left ventricular volumes. In the placebo group a negative correlation was found between plasma aldosterone at days 5-7 and the subsequent increase in left ventricular ejection fraction (r = -0.77, P = 0.006) during the study period. Although circulating neurohormones were not significantly influenced by enalapril treatment, it is concluded that enalapril may influence the relationship found between sustained neurohormonal activation and left ventricular remodelling after acute myocardial infarction.
 ...
PMID:Neurohormonal effects of early treatment with enalapril after acute myocardial infarction and the impact on left ventricular remodelling. 840 42

The concept of "cardioprotection" with ACE inhibitors has evolved over the last decade. In the 1980s, protective benefits of ACE inhibitors in hypertension were established, regression of left ventricular hypertrophy was demonstrated, and improved ventricular function and survival in mild-to-moderate and severe congestive heart failure was documented. A further "protective" role of ACE inhibitors in coronary artery disease is emerging as more attention is focused on the concept of local tissue renin-angiotensin systems. Recent contributions to the literature describe significant benefits of ACE-inhibitor therapy in acute myocardial infarction, including suppression of ventricular arrhythmias and reduction of both early and late ventricular dilation, preservation of left ventricular function, and improved survival. All of the above effects can be considered "cardioprotective." However, as new benefits are reported in the 1990s, a broadened view of "cardiovascular protection" emerges from investigative studies in the literature. ACE inhibitors may reduce tolerance to nitrates, reduce angina in some but not all studies, and limit smooth muscle cell proliferation (and perhaps restenosis) induced by experimental balloon angioplasty. Local vascular effects may attenuate atherosclerotic changes in the arterial wall in experimental animals and may decrease the incidence of aneurysm formation in hypertensive animals. The effectiveness of ACE inhibitors in acute myocarditis, suggested by reports that captopril may reduce lesions of murine myocarditis when administered early after infection with coxsackievirus B3, requires clinical confirmation. Despite these apparently diverse "cardiovascular protective" consequences of ACE inhibitor therapy, the mechanism(s) of action of these agents remain to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardioprotection with angiotensin-converting enzyme inhibitors: redefined for the 1990s. 843 34

Ischemic heart disease is the major etiology for the development of congestive heart failure. Patients with acute myocardial infarction have a greatly increased risk for mortality and for manifesting symptomatic heart failure. This risk is not a uniform one but is greatly augmented in patients with a more extensive infarction and, consequently, a more depressed global ventricular function. An important concept that was derived from studies in rats with myocardial infarction and has been confirmed in patients is that ventricular enlargement, which has been shown to be a marker for an adverse outcome, can be a progressive process that leads to further deterioration of ventricular performance. Both experimental and early clinical studies have indicated that chronic therapy with an angiotensin converting enzyme inhibitor may attenuate this progressive ventricular enlargement. More definitive clinical trials are currently under way to determine whether this form of therapy, which may diminish the extent of ventricular enlargement over time, will result in an improvement in survival and in the prevention of the development of congestive heart failure. The addition of this pharmacological therapy to that of the primary prevention of atherosclerosis and that of the limitation of infarct size should make a substantial impact on the reduction of the incidence of congestive heart failure.
 ...
PMID:Development and prevention of congestive heart failure following myocardial infarction. 848 27

Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58,000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50 mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50 mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Captopril. A review of its pharmacology and therapeutic efficacy after myocardial infarction and in ischaemic heart disease. 853 52

The current treatment of survivors of acute myocardial infarction is now largely based on sound scientific principles, supported by the results of large and well-designed clinical trials. These have demonstrated that aspirin, anticoagulants, beta-blockers, angiotensin converting enzyme inhibitors, and lipid-lowering agents reduce mortality and reinfarction in selected groups of patients. It remains uncertain whether these different treatments are additive and whether there are beneficial or undesirable interactions. In addition to informing us about the effectiveness or otherwise of these and other drugs, we have learned much about the conduct, analysis, and limitations of clinical trials in this context. The selection of patients for the various treatments is a matter of opinion because the results of the trials are open to a variety of interpretations. In assessing trials, one must be sure that they have been conducted on the intention to treat principle and that surrogate and composite end points have not been inappropriately used. In applying the results of trials to one's own practice, one must take into account the problems of extrapolation and subgroup analysis.
 ...
PMID:Treatment for survivors of acute myocardial infarction: what have we learned from large intervention trials? 856 66

Acute myocardial infarction occurs with increasing frequency with advancing age, and older patients with acute MI are at increased risk of a variety of complications including congestive heart failure, arrhythmias and conduction disturbances, myocardial rupture, cardiogenic shock, and death. Older patients thus comprise a high-risk subgroup of the MI population who consequently may derive substantial benefit from appropriately selected therapeutic interventions. At the same time, many interventions are associated with increased risks in the elderly, so that individualization of treatment is essential in all patients. Optimal therapy is thus based on a careful risk-benefit assessment of the available treatment options in conjunction with information on patient preferences and other relevant factors. Though many therapeutic trials of patients with acute MI have either excluded elderly patients or enrolled too few older subjects to permit definitive conclusions, sufficient data are available to make specific recommendations in several areas. As shown in Table 6, therapies of proven value in the acute-phase treatment of elderly patients with MI include aspirin and thrombolysis. Intravenous beta blockers are likely to be of benefit as well, and long-term oral beta blockade after MI is clearly beneficial. ACE inhibitors are of proven value in the long-term management of patients with left ventricular dysfunction (ejection fraction less than 40%), but initiation of an ACE inhibitor should probably be delayed for 48 to 72 hours in most cases. The role of other agents including nitrates, magnesium, diltiazem, and verapamil requires further clarification, but anti-arrhythmic drugs and dihydropyridine calcium antagonists should generally be avoided in the absence of specific indications for their use. Finally, though the role of catheterization and revascularization in elderly patients with acute MI requires additional study, current data indicate that age alone should not be considered a contraindication to these procedures. As the age of the population continues to rise, the number of older patients at risk of acute MI also increases. Though progressively more sophisticated interventions may ultimately result in sizable reductions in post-MI morbidity and mortality, given the high risk of adverse outcomes in this population the best treatment is prevention. Thus, the greatest potential for the future, as well as the greatest challenge, is to develop more effective strategies for preventing atherosclerosis and for conquering the epidemic of coronary heart disease.
 ...
PMID:Therapy for acute myocardial infarction. 865 55

Data on all patients with acute myocardial infarction who were treated in the ten hospitals in Health region 1 in Norway were extensively analysed over a two month period. Of all the 487 patients 32% received thrombolytic treatment; i.e 36% of those with definite or suspected myocardial infarction on admission. Thrombolytics were withheld, mainly because only 58% of the patients showed ST elevation or bundle branch block on their ECG, and because of a long delay from onset of symptoms to admission to hospital. With increasing age use of thrombolytics decreased, and high age seemed to some degree to act as a contraindication. Relative contraindications such as history of stroke or peptic ulcer contributed modestly to the limited use of thrombolytics. Aspirin was used by 72% of the patients, and either aspirin or anticoagulants in 87%. At six month follow-up 50% used aspirin and 32% warfarin. Betablockers were given to 57% of the patients in hospital, but were not used to any extent in the acute phase of the disease; at six months the proportion of patients on betablockers was about the same. Oral nitrates were used more extensively than betablockers and there is a clear indication that angiotensin converting enzyme inhibitors are used increasingly for secondary prevention.
 ...
PMID:[Use of thrombolytic agents and other drugs in acute myocardial infarction]. 865 33

In this double-blind placebo-controlled study with enalapril, 74 patients with acute myocardial infarction were followed at 0, 7, 30, 60 and 180 days after the event. Platelets and leukocytes were activated during the first 7 days. During the 6-month period fibrinogen, leukocytes, elastase, and B beta 30-43 remained elevated in 50, 15, 30 and 80% of the patients, respectively, but there was no detectable angiotensin converting enzyme activity in platelets. Enalapril did not modulate fibrinogen, leukocyte count or elastase, while B beta 30-43 peptide showed decreased levels, although the proportion of patients with values above the reference limit did not differ from placebo. In conclusion, in the 6-month post acute myocardial infarction period, while platelet function is activated only during the first week after acute myocardial infarction, fibrinogen and leukocyte function continue to be activated throughout the 6 months in a considerable proportion of patients. These signs may indicate an ongoing atherosclerotic process. Enalapril has no major influence on these reactivities.
 ...
PMID:Platelet and leukocyte activation after myocardial infarction. Influence of enalapril. 868 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>