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 antiarrhythmic effects of captopril, an angiotensin converting enzyme (ACE) inhibitor, were investigated in an in vivo rat model of coronary artery ligation. Captopril (0.3-3 mg kg-1) or saline were administered by intravenously 10 min before coronary ischaemia. The left main coronary artery was then occluded for 7 min, followed by 7 min of reperfusion. Captopril caused a marked decrease in mean arterial blood pressure which was transient at 0.3 and 1 mg kg-1, and at doses of 1 and 3 mg kg-1, it produced marked bradycardia. The incidence of ventricular tachycardia (VT) on ischaemia was significantly reduced the captopril at a dose of 3 mg kg-1 only and on reperfusion at doses of 1 and 3 mg kg-1. At the same doses, captopril significantly reduced the mean duration of ventricular fibrillation (VF) on reperfusion. The incidence of mortality resulting from reperfusion-induced irreversible VF in the control group decreased from 42.9% to 14.3% (NS), 21.4% (NS) and 7.7% (P < 0.05) in captopril at 0.3, 1 and 3 mg kg-1, respectively. Our results indicate that captopril appears to limit the arrhythmias following reperfusion and this may be due in part to the antiischemic effect associated with bradycardia and vasodepression.
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PMID:Effects of captopril on ischaemia-reperfusion-induced arrhythmias in an in vivo rat model. 866 45

The antiarrhythmic effects of captopril, a sulphydryl-containing angiotensin converting enzyme (ACE) inhibitor, were compared with those of the nonsulphydryl-containing ACE inhibitor lisinopril and the sulphydryl-containing agent glutathione in an in vivo rat model of coronary artery ligation. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Captopril (3 mg kg-1) and lisinopril (0.1, 0.3 or 1 mg kg-1) caused marked decreases in mean arterial blood pressure (BP) and heart rate, whereas glutathione (5 mg kg-1) had no effect on them. The incidence of ventricular tachycardia (VT) on ischemia and reperfusion was significantly reduced by captopril and lisinopril. Captopril and 1 mg kg-1 lisinopril also significantly decreased the number of VEB during occlusion and the duration of VT on reperfusion, respectively. These drugs also attenuated the incidence of reversible ventricular fibrillation (VF) and the number of ventricular ectopic beats (VEB) during reperfusion. However, glutathione only reduced the incidence of VT on reperfusion, significantly. These results suggest that, in this experimental model, ACE inhibitors limit the arrhythmias following ischemia-reperfusion and free radical scavenging action of these drugs does not have a major contributory role in their protective effect.
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PMID:Protective effect of ACE inhibitors on ischemia-reperfusion-induced arrhythmias in rats: is this effect related to the free radical scavenging action of these drugs? 941 67

Attenuation of ischaemia-reperfusion induced arrhythmias by several angiotensin converting enzyme (ACE) inhibitors, such as captopril, has been demonstrated. The role of prostaglandin synthesis stimulation in this protective effect of ACE inhibition was evaluated in an in vivo rat model. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Captopril (3 mg kg-1) and a prostaglandin synthesis inhibitor, indomethacin (2 mg kg-1) alone or together were administered by intravenous (i.v.) injection 10 min before occlusion. Captopril reduced the incidence of ventricular tachycardia (VT) and the number of ventricular ectopic beats (VEB) on ischaemia and reperfusion as well as the incidence of reversible ventricular fibrillation (VF) on reperfusion. These protective effects of captopril against ischaemia-reperfusion-induced arrhythmias were prevented by indomethacin. Captopril also caused a sustained decrease of preocclusion values in the arterial blood pressure (BP) and heart rate (HR), whereas in the presence of indomethacin, captopril had no significant effect on either HR or arterial BP values except the heart rate value just before occlusion. Indomethacin alone did not affect either the severity of arrhythmias or the haemodynamic parameters. These results suggest that, in this experimental model, the protective effects of ACE inhibitors on the arrhythmias following ischaemia-reperfusion are mediated by the stimulation of prostaglandin synthesis and the haemodynamic effects of these drugs may have a contributory role in their protective effect.
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PMID:The role of prostaglandin synthesis stimulation in the protective effect of captopril on ischaemia-reperfusion arrhythmias in rats in vivo. 942 19

Reperfusion arrhythmias originate as a consequence of the complex of cellular and humoral reactions accompanying the opening of coronary artery. As the primary cause of their generation are considered the chemically defined substances that are produced and accumulated in myocardium during reperfusion. The key role id ascribed to free oxygen radicals but of importance are also other substances such as calcium, thrombin, platelet activating factor, inositol triphosphate, angiotensin II and others. These chemical mediators of reperfusion arrhythmias operate as modulators of cellular electrophysiology causing the complex changes at the level of ion channels. It is supposed that in the genesis of reperfusion arrhythmias unlike ischemic arrhythmias operate nonreentrant mechanisms such as abnormal or enhanced automacy and triggered activity due to afterdepolarizations. As a typical reperfusion arrhythmia is considered an early (within 6 hours after start of thrombolysis), frequent (> 30 episodes/hour) and repetitive (occurring during > 3 consecutive hours) accelerated idioventricular rhythm (AIVR). AIVR with such characteristics has a high specificity and positive predictive accuracy but relative low sensitivity as a predictor of reperfusion. Thus, in occurrence of AIVR, recanalization of infarction-related coronary artery is very probable, but in absence of AIVR, reperfusion is still not excluded. The following arrhythmias are regarded also as markers of reperfusion: frequent premature ventricular complexes (> twofold increase in frequency within 90 minutes after the start of thrombolysis), a significant increase of episodes in nonsustained ventricular tachycardia, sinus bradycardia and probably also high degree atrioventricular blocks. At present, there is no definite evidence, as to whether sustained ventricular tachycardia and especially ventricular fibrillation can be caused by reperfusion. Reperfusion arrhythmias are an important noninvasive marker of successful recanalization of infarction-related coronary artery. However, they are also a sign of reperfusion injury and a finding which may limit the favourable effect of reperfusion. In account of that, there is a very intensive search for pharmacologic interventions which could protect or attenuate the reperfusion injury and thereby also the genesis of reperfusion arrhythmias. Although promising results were obtained with many substances antagonizing the effects of mediators of reperfusion injury, there is no definite recomendation for their use under clinical conditions. However, the results from the latest clinical trials with ACE inhibitors are very promising. These trials render relative conclusive evidence, that ACE inhibitors could have a protective effect against reperfusion arrhythmias. (Ref. 89, Tab. 1.)
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PMID:[In Process Citation] 966 38

Sudden death accounts for about 35% of the mortality of cardiac failure and its incidence does not decrease with the use of angiotensin converting enzyme inhibitors. Non-sustained ventricular tachycardia on Holter monitoring, late ventricular potentials and tachycardia induced by programmed ventricular stimulation have no formal predictive value of sudden death, underlining the varied character of the mechanisms underlying sudden death during cardiac failure. Sustained ventricular tachycardia degenerating to ventricular fibrillation is only one of the rhythmic factors implicated together with inaugural ventricular fibrillation, bradyarrhythmias and electromechanical dissociation. The underlying cardiac disease plays a role in the initiation of the fatal arrhythmia. In coronary artery disease, recurrent acute ischaemia is the principal trigger factor in patients who often have triple vessel disease. This explains the fact that classic markers of arrhythmia in the post-infarction period, which are only the reflection of the arrhythmogenic substrate of ventricular tachycardia, usually due to reentry around the fibrous scar of the infarct, are not valid in patients with progressive ischaemic cardiomyopathy. The most effective antiarrhythmic treatment in this type of patient is the prevention of ischaemia, when possible. In primary dilated cardiomyopathy, the mechanism underlying sudden death could be different at each stage. In NYHA Stages I and II, ventricular tachyarrhythmias could play a major part in unexpected sudden death in patients whose stable haemodynamic status suggested a more prolonged survival. The value of an implantable defibrillator would seem to be proved in this group of patients, at least in secondary prevention. In Stages III and IV, ventricular arrhythmias only indicate the degree of ventricular dysfunction and sudden death may follow bradyarrhythmias and electromechanical dissociation due to the precarious haemodynamic status.
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PMID:[Sudden death and chronic cardiac insufficiency]. 989 14

Reperfusion arrhythmias originate as a consequence of the complex of cellular and humoral reactions accompanying the opening of coronary artery. As the primary cause of their generation are considered the chemically defined substances that are produced and accumulated in myocardium during reperfusion. The key role is ascribed to free oxygen radicals but of importance are also other substances such as calcium, thrombin, platelet activating factor, inositol triphosphate, angiotensin II and others. These chemical mediators of reperfusion arrhythmias operate as modulators of cellular electrophysiology causing the complex changes at the level of ion channels. It is supposed that in the genesis of reperfusion arrhythmias unlike ischemic arrhytmias operate nonreentrant mechanisms such as abnormal or enhanced automacy and triggered activity due to afterdepolarizations. As a typical reperfusion arrhythmia is considered an early (within 6 hours after start of thrombolysis), frequent (> 30 episodes/hour) and repetitive (occurring during > 3 consecutive hours) accelerated idioventricular rhythm (AIVR). AIVR with such characteristics has a high specificity and positive predictive accuracy but relative low sensitivity as a predictor of reperfusion. Thus, in occurrence of AIVR, recanalization of infarction-related coronary artery is very probable, but in absence of AIVR, reperfusion is still not excluded. The following arrhythmias are regarded also as markers of reperfusion: frequent premature ventricular complexes (> twofold increase in frequency within 90 minutes after the start of thrombolysis), a significant increase of episodes in nonsustained ventricular tachycardia, sinus bradycardia and probably also high-degree atrioventricular blocks. At present, there is no definite evidence, as to whether sustained ventricular tachycardia and especially ventricular fibrillation can be caused by reperfusion. Reperfusion arrhythmias are an important noninvasive marker of successful recanalization of infarction-related coronary artery. However, they are also a sign of reperfusion injury and a finding which may limit the favourable effect of reperfusion. In account of that, there is a very intensive search for pharmacologic interventions which could protect or attenuate the reperfusion injury and thereby also the genesis of reperfusion arrthythmias. Although promising results were obtained with many substances antagonizing the effects of mediators of reperfusion injury, there is no definite recommendation for their use under clinical conditions. However, the results from the latest clinical trials with ACE inhibitors are very promising. These trials render relative conclusive evidence, that ACE inhibitors could have a protective effect against reperfusion arrhythmias. (Ref. 89, Tab. 1.)
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PMID:[Reperfusion arrhythmias]. 991 46

Congestive heart failure (CHF) is growing epidemiologic and clinical problem, and is the only common cardiovascular condition that is increasing in incidence, prevalence and mortality. During last years numerous clinical trial have been conduced evaluating the effect of various treatment procedures on clinical endpoints in patients with CHF. The major risk factor for CHF are hipertension and atherosclerotic vascular diseases, and now it is clear that aggressive treatment of hypertension and hyperlipidemia can be effective in preventing CHF. Treatment strategies for CHF are aimed at preventing and delaying progression of the disease and improving survival. In the treatment of CHF diuretics are at present the first drugs line for patients with fluid retention and are necessary to relieve symptoms but cannot halt progression or improve the prognosis of CHF. Angiotensin-converting enzyme inhibitors (ACE inhibitors) therapy has been shown to decrease mortality and progression of CHF and should be used early in patients with left ventricular dysfunction whether they have symptomatic or asymptomatic CHF. Digoxin therapy is associated with decrease in the risk of worsening CHF irrespective of rhythm, systolic function, severity of CHF or therapy with ACE inhibitors. In patients with symptomatic CHF due to systolic dysfunction the addition of diuretics and digoxin appears to reducing worsening CHF without improving survival. Other than digoxin oral inotropic agents (amrinone, pimobendan, vesnarinone, ibopamine) increase mortality in patients with CHF and have not improved symptom status and other clinical endpoints during long-term therapy. Hydralazine and isosorbide dinitrate administrated in combination are less effective alternative to ACE inhibitors. Beta-blockers and particular carvedilol may prolong survival and decrease worsening CHF when used in combination with digoxine, diuretics and ACE inhibitors. Beta-blockers therapy improve hemodynamics, LVEF and functional status patients with CHF and the ideal candidate for this therapy is stable patients with NYHA II-III CHF due to nonischemic cause. Calcium antagonists do not appear to be useful in patients with CHF, although amlodipine and mibefradil appears to be safe for treatment of angina or hypertension in this group. On the basis of current data, antiarrhythmic agents should not be given to patients with CHF free from arrhythmia but those with sustained ventricular tachycardia or ventricular fibrillation amiodaron appears to be safe.
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PMID:[Trends in pharmacological treatment of congestive heart failure]. 1036 2

The effects on the responses to coronary artery occlusion of a combined ACE/NEP inhibitor (Z13752A) were examined in anaesthetized dogs. A 1 h infusion of Z13752A (128 microgram kg(-1) min(-1) intravenously) decreased arterial blood pressure (by 11+/-3%; P<0. 05) and increased coronary blood flow (by 12+/-4%, P<0.05). There were no other significant haemodynamic changes. Z13752A inhibited both NEP and ACE enzymes both in dog plasma and in tissue (lung ACE; kidney NEP). Pressor responses to angiotensin I in vivo were inhibited and systemic vasodilator responses to bradykinin were potentiated. When the left anterior descending coronary artery was occluded for 25 min, Z13752A markedly reduced the severity of the resultant ventricular arrhythmias. No ventricular fibrillation (VF) occurred (compared to 7/16 in the controls; P<0.05), and ventricular tachycardia (VT) was reduced (VT in 2/9 dogs treated with Z13752A cp. 16/16 of controls; episodes of VT 0.2+/-0.1 c.p. 10.7+/-3.3; P<0. 05). Reperfusion of the ischaemic myocardium led to VF in all control dogs but occurred less frequently in dogs given Z13752A (survival from the combined ischaemia-reperfusion insult 67% c.p. 0% in controls; P<0.05). Z13752A reduced two other indices of ischaemia severity; epicardial ST-segment elevation and inhomogeneity of electrical activation. These protective effects of Z13752A during ischaemia and reperfusion were abolished by the administration of icatibant (0.3 mg kg(-1), i.v.) a selective antagonist of bradykinin at B(2) receptors; the ischaemic changes in dogs given both icatibant and Z13752A were similar to those in the controls. We conclude that this ACE/NEP inhibitor is effective at reducing the consequences of coronary artery occlusion in this canine model and that this protection is primarily due to potentiation of released bradykinin. British Journal of Pharmacology (2000) 129, 671 - 680
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PMID:The effects of Z13752A, a combined ACE/NEP inhibitor, on responses to coronary artery occlusion; a primary protective role for bradykinin. 1068 91

Life threatening hyperkalaemia (> 7.0 mmol/l) is commonly associated with acute renal failure. Moderate hyperkalaemia (6.1-6.9 mmol/l) is also common and well tolerated in patients with chronic renal failure. Renal failure is the most common cause of hyperkalaemia although other causes to consider include drugs (potassium sparing diuretics, angiotensin converting enzyme inhibitors), hyperglycaemia, rhabdomyolysis and adrenal insufficiency. Hyperkalaemia affects the cardiac conducting tissue and can cause serious arrhythmias including ventricular fibrillation and asystolic arrest. Therefore it is important to treat hyperkalaemia promptly in the emergency department. This paper evaluates the therapeutic options available for treatment of hyperkalaemia.
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PMID:The management of hyperkalaemia in the emergency department. 1190 81

Ventricular arrhythmias are particularly common in cardiac failure and their mechanisms are very complex. The prevention of these ventricular arrhythmias is only worthwhile if it results in benefits in terms of reduction of the risk of sudden death and in improvement in life expectancy. However, the relationship between complex ventricular arrhythmias and sudden death is far from established. The first problem is, therefore, to select the patients at high risk of sudden death. Unfortunately, there are no reliable markers of arrhythmic risk; only patients at low risk can be reasonably well identified on clinical and haemodynamic assessment and the results of ambulatory and signal averaged ECG. When an antiarrhythmic treatment seems to be required, the choice is very limited in practice. There is no role for Class I antiarrhythmics to play in this indication. Amiodarone, with its complex electrophysiological profile enabling an interaction with all potential mechanisms of ventricular arrhythmias, is a first-line drug in cardiac failure because of its efficacy and good myocardial tolerance. However, the benefits of amiodarone therapy in terms of reduction of global mortality have not been demonstrated, especially in view of the discordance between the results of the GESICA and CHF STAT trials. On the other hand, the value of betablockers, whether conventional molecules like bisoprolol (CIBIS II study) or metoprolol (MERIT-HF study), or molecules with a special profile such as carvedilol, has been clearly established. In association with conventional diuretics and angiotensin converting enzyme inhibitors, they reduce global mortality by about 35% and sudden death by 40%. However, the future possibly lies with non-pharmacological approaches such as the implantable defibrillator, at least in patients clearly identified as being at high risk of arrhythmic death, resuscitated from cardiorespiratory arrest due to documented ventricular fibrillation or presenting with haemodynamically poorly tolerated ventricular tachycardia. The automatic defibrillator could improve the prognosis of these patients, irrespective of their functional status (NYHA, Classes I, II or III). In practice, "rhythmological" management of cardiac failure cannot be dissociated from the haemodynamic and neuro-hormonal aspects of the affection, and only a multi-factorial approach is being realistic.
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PMID:[Cardiac insufficiency: prevention of ventricular arrhythmias]. 1083 85


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