Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blockade of the renin-angiotensin-aldosterone system (RAAS) has been shown to be effective in reducing morbidity and mortality in patients with symptomatic left ventricular dysfunction. Angiotensin converting enzyme inhibitors (ACE-I) should be administered to all patients with symptomatic left ventricular dysfunction unless contraindicated or not tolerated. Although ACE-Is are effective, there is reason to believe that further blockade of the RAAS by aldosterone antagonists and/or alternative means of blocking the RAAS by use of renin inhibitors or angiotensin II receptor blocking agents may have an important role in the future. The finding in the SOLVD and SAVE trials that ACE-Is are effective in reducing recurrent ischemic events in patients with left ventricular dysfunction also holds great promise for the future, not only for patients with left ventricular dysfunction but also as a possible secondary prevention of ischemic heart disease in patients without left ventricular dysfunction.
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PMID:Blockade of the renin-angiotensin system. Effect on mortality in patients with left ventricular systolic dysfunction. 818 Oct 19

The term heart failure has become a label for more than one clinical entity. For many years heart failure has been used to denote patients with various heart diseases who have begun to suffer from fluid retention, pulmonary venous hypertension, or systemic venous hypertension, either alone or in combination. More recently, the term heart failure has been applied to the combination of effort intolerance and reduced left ventricular contractility due to ischemic heart disease or other myocardial disease. Comparison of the results of epidemiological studies and therapeutic trials is complicated by variation in the composition of the patient populations selected for study. Drug treatment of heart failure remains fairly empirical. Distinction should be made between immediate or prognostic benefits related to the etiological diagnosis, and benefits related specifically to prevention and relief of, for example, fluid retention, rhythm disturbances, or ventricular hypertrophy. The response of individual patients to several forms of drug treatment, including digoxin, ACE inhibitors, and beta-blockade, is unpredictable. Prospective identification of patients liable to respond well to these drugs is not yet possible, but would greatly assist the choice of treatment. At present, trial of therapy is required in each patient to establish benefit and to avoid long-term treatment of nonresponders.
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PMID:The management of heart failure: a matter of definition? 824 Oct 9

The anti-ischemic properties of the ACE inhibitor ramiprilat (ram) were investigated in electrically driven Langendorff hearts from rabbits whose endogenous angiotensin-I content has been previously shown to be very low (constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). Cumulative concentration-response curves showed that the reduction in global coronary flow (CF) by exogenous angiotensin-I was concentration dependently inhibited by ram (P < 0.05). Myocardial ischemia (MI) was induced by occlusion of a left coronary artery branch and MI was quantified by NADH surface fluorescence photography. MI was significantly enlarged (+23%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol/l). Addition of ram (10(-8) mol/l) to the perfusion buffer simultaneously with angiotensin-I, completely prevented the reduction of CF by angiotensin-I (P > 0.05) and significantly diminished MI even below control values (-25%) (P < 0.05). In the absence of exogenous angiotensin-I, ram alone (10(-8) mol/l) did not significantly enhance CF (P > 0.05), supporting findings demonstrating a very low endogenous angiotensin-I content in isolated rabbit hearts. However, ram alone (10(-8) mol/l) significantly diminished MI (-24%) (P < 0.05). We conclude that ram does possess direct cardioprotective properties that are independent of the inhibition of angiotensin-II generation but that may be related to potentiation of the effects of bradykinin.
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PMID:Cardioprotection by ramiprilat in isolated rabbit hearts. 824 56

There are multiple mechanisms whereby ACE inhibitors could be beneficial during myocardial ischemia and reperfusion, including: i) reduced formation of angiotensin II, ii) decreased metabolism of bradykinin, iii) antioxidant activity, and iv) possibly other unknown mechanisms. Reduced formation of angiotensin II should be beneficial because this peptide exerts several actions that are potentially detrimental to the ischemic/reperfused myocardium, including vasoconstriction, increased release of norepinephrine, stimulation of phospholipase C and/or A2, and increased afterload with an attendant increase in oxygen demands. Reduced metabolism of bradykinin could be beneficial by increasing myocardial glucose uptake, by causing vasodilation, and by stimulating production of endothelium-derived relaxing factor and prostacyclin. Although earlier studies suggested that sulfhydryl-containing ACE inhibitors scavenge superoxide anions, recent data have shown that these drugs scavenge hydroxyl radical and hypochlorous acid with no effect on superoxide anion. Studies in isolated hearts have demonstrated that ACE inhibitors attenuate the metabolic, arrhythmic, and contractile dearrangements associated with ischemia and reperfusion, and have suggested that such beneficial effects are mediated by potentiation of bradykinin and/or increased synthesis of prostacyclin. Studies in models of myocardial stunning after brief (15-min) ischemia in vivo (anesthetized dogs) suggest that ACE inhibitors enhance the recovery of contractile function after a single brief ischemic episode. No data are available regarding the effect of these drugs on myocardial stunning after a prolonged, partly reversible episode, after multiple consecutive brief ischemic episodes, and after global ischemia. The mechanism for the salutary effects of ACE inhibitors on stunning remains a mystery. It may involve an antioxidant action (in the case of thiol-containing molecules) or potentiation of prostaglandins (in the case of non-thiol-containing molecules). What is clear is that the enhanced recovery of function effected by these drugs is not due to hemodynamic effects, inhibition of the converting enzyme per se, or an "antischemic" action (since the drugs were effective when given at the time of reperfusion). The effects of ACE inhibitors on myocardial infarct size remain controversial. Further studies will be necessary to conclusively establish whether ACE inhibitors can protect against the detrimental effects of myocardial ischemia and reperfusion. Nevertheless, the evidence provided thus far is encouraging and warrants an in-depth assessment of the role of these drugs in attenuating myocardial ischemia/reperfusion injury.
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PMID:Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview. 835 31

Treatment of hypertension reduced markedly (by more than 40%) the prevalence of cerebrovascular attacks, the prevalence of cardiac failure, malignant hypertension and ophthalmological complications of hypertension. The impact of antihypertensive treatment on the incidence of ischaemic heart disease is less marked. The wide use of diuretics and beta-blockers is supported by the fact that large studies of antihypertensive treatment revealed that they reduced the cardiovascular mortality and morbidity in a marked way. On the other hand, diuretics exert a negative effect on insulin resistance, glucose tolerance, cholesterol and may lead to hypokalaemia and hyperuricaemia. Non-selective beta-blockers are not optimal from the aspect of the risk profile of hypertensive patients. Therefore there is justified hope that wider use of calcium antagonists, beta-blockers of the third generation, ACE inhibitors and selective alpha 1 blockers will have a greater impact on IHD, as these drugs do not exert a negative effect on metabolic risk factors. At present an individual approach to treatment which takes into account other diseases present or complications of hypertension, in particular diabetes and hyperlipoproteinaemia, is the basic approach so far and the basis of therapeutic tactics.
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PMID:[Current trends in antihypertensive therapy: pro and con]. 837 69

The endogenous activity of the local renin-angiotensin system (RAS) and the anti-ischaemic properties of captopril were investigated in electrically driven rabbit Langendorff hearts (constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol.l-1). Cumulative concentration-response curves showed no significant difference (P > 0.05) between the reduction of the global coronary flow (CF) by exogenous angiotensin-I or angiotensin-II (EC50 = 10(-10) mol.l-1). It is concluded that the local RAS in isolated rabbit hearts is highly sensitive, whereas its endogenous activity is very low due to very low endogenous angiotensin-I content. Myocardial ischaemia (MI) was induced by the occlusion of a left coronary artery branch and MI was quantified from NADH surface fluorescence photography. MI was significantly enlarged (+35%) (P < 0.05) by exogenous angiotensin-I (6 x 10(-9) mol.l-1). The reduction in CF and the increment in MI by angiotensin-I could be completely prevented by adding captopril at a low concentration (10(-6) mol.l-1) to the perfusion buffer. In the absence of exogenous angiotensin-I, captopril alone (10(-6) mol.l-1) neither significantly enhanced CF (P > 0.05), nor diminished MI (P > 0.05), supporting the finding of very low endogenous activity of the local RAS in this model. We, moreover, conclude that at a low concentration (10(-6) mol.l-1) captopril does not possess direct cardioprotective properties independent of its ACE inhibiting action.
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PMID:Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril. 843 77

Coronary reserve plays an important role in myocardial oxygen supply. During rest, oxygen consumption is near to maximal. An increase in myocardial oxygen demand can only be covered by an increase in coronary flow by dilation of coronary vessels. The maximal achievable rise in coronary blood flow is called coronary reserve. Coronary reserve is not only enhanced in patients with coronary artery disease but also in patients with disorders of coronary microcirculation for example in arterial hypertension. The following review will deal especially with disorders of the microcirculation in arterial hypertension. The impairment of coronary reserve is a result of structural and functional alterations. Structural alterations include an increase in media wall thickness of the small coronary arteries and a reduction of coronary capillaries. Extravascular myocardial forces which determine coronary resistance include myocardial hypertrophy and qualitative changes of myocardium like interstitial and perivascular fibrosis. The role of functional alterations like endothelial related vasomotion is discussed. The renin-angiotensin system modulates the growth of the small muscle cells of the vessels and induces protooncogenes and other growth factors. Therefore the renin-angiotensin system may also play an important role in hypertensive remodeling. Hypertensive coronary microangiopathy is diagnosed by exercise stress test and ST-segment-monitoring over 24 hours to show myocardial ischemia. Also nuclear medicine technics can be used if conventional methods of showing ischemia don't work. The diagnosis is definite if the determination of coronary reserve shows that the maximal coronary blood flow is not achieved. Coronary flow can be measured by the argon-gas-method, the thermodulation-technic or by the doppler-method. Also by nuclear medicine technics (PET) the coronary flow reserve can be determined. The advantages of these methods are discussed. In experimental studies calcium-channel-blockers, ACE-inhibitors and moxonidine showed an increase in density of capillaries and also a reduction of myocardial hypertrophy, which both result in an improvement of coronary reserve. Clinical studies of our group demonstrate that coronary microangiopathy in hypertensives can be improved by calcium-channel-blockers and ACE-inhibitors after one year treatment. Beta-receptor-blockers show no clear improvement of coronary reserve. It has to be shown by further studies whether the improvement of coronary reserve is more important for prognosis than the regression of myocardial hypertrophy.
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PMID:[Coronary microangiopathy in hypertensive heart disease: pathogenesis, diagnosis and therapy]. 858 95

The rationale for beta-blockade in heart failure is now well established. Heart failure mortality, which is predicted by neurohormonal activation, remains high despite modern treatment including ACE inhibition, and additional neurohormonal blockade has further therapeutic potential. Previous clinical trial experience in heart failure, most of which has been in patients with idiopathic cardiomyopathy, indicates consistent improvement in ventricular function although variable changes in symptoms and exercise performance. However, the major burden of heart failure occurs in patients with ischaemic heart disease and in this respect it is notable that beta-blockade following myocardial infarction confers significant mortality benefit in subgroups with heart failure. The Australia and New Zealand carvedilol heart failure study is the largest completed study of beta-blocker treatment in patients with heart failure of ischaemic aetiology, including 415 patients randomized to carvedilol or placebo and indicating excellent tolerability of a titrated dose regimen and improved ventricular function after 6 months of treatment. An overview of all currently available randomized clinical trials of beta-blockade in heart failure, which includes more than 1600 patients, indicates a mortality risk reduction of approximately 20% but with wide confidence intervals. A large scale trial with several thousand patients is required to detect reliably a plausible 15-20% mortality reduction with beta-blockade in heart failure. The dissociation of clinical and mortality effects demonstrated with other heart failure treatments indicates the necessity for an appropriately powered mortality study which could define a major improvement in heart failure therapy for the future.
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PMID:Beta-blockers in heart failure. Future directions. 873 70

ACE inhibitors have the potential to affect myocardial ischaemia in patients with asymptomatic ventricular dysfunction and ischaemic cardiomyopathy after long-term treatment. However, anti-ischaemic effects are virtually absent in stable effort angina during short-term therapy, which suggests different mechanisms of action in different patient subtypes. Long-term treatment in left ventricular dysfunction may lead to a reduction in myocardial oxygen demand and ischaemia as a result of ventricular remodelling, possibly supported by structural coronary vascular effects, i.e., an improved endothelial function and vasodilator capacity. An alternative mechanism by which ACE inhibitors may affect ischaemia, is through modulation of ischaemia-induced neurohormonal activation and subsequent systemic vasoconstriction. Depending on the severity of ischaemia, pronounced catecholamine activation and stimulation of the circulating renin-angiotensin system occur, accompanied by systemic vasoconstriction and an increase in afterload. These changes are marked in patients with left ventricular dysfunction. Moreover, a change from net catecholamine release to uptake in the ischaemic area is observed. Although the clinical significance of the latter observation is still unclear, sympathetic activation may lead to coronary vasoconstriction in stenotic areas where normal endothelium-dependent coronary vasodilatation has become impaired. In the resting patient, enalaprilat and perindoprilat significantly reduce myocardial ischaemia, not by a direct effect on the oxygen supply-demand ratio, but through modulation of neurohormonal activation, in particular of sympathetic activation during ischaemia, and, subsequently, by preventing systemic vasoconstriction. These effects are pronounced in left ventricular dysfunction, at least where perindoprilat is concerned. The possibility that ACE inhibitors improve endothelial function in concert with their modulating effects on ischaemia-induced neurohormonal activation and hence influence the occurrence of myocardial ischemia during long-term treatment needs further evaluation.
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PMID:Anti-ischaemic effects of converting enzyme inhibitors: underlying mechanisms and future prospects. 882 63

Ischaemic heart disease is a perfect example of variability. The official mortality statistics in Europe show a gradient from 1 to 5. France is a zone at low risk even if deaths of undetermined causes are taken into account. This gradient is confirmed by the data from the Registries of the MONICA project. In France, the official mortality figures show a decrease of 28% in coronary mortality between 1985 and 1991 in men, throughout France. The differences in incidence of myocardial infarction between Lille and Toulouse in the MONICA project are not important but the differences in mortality are worrying. Between 1985 and 1991, the three registries show a 7% decrease in mortality (p < 0.001) and a 25% decrease in recurrences (p < 0.001) with an increase in primary infarcts of 8.3% (p < 0.05). There has been an increase in the prescription of betablockers, thrombolytics, ACE inhibitors and aspirin during the acute phase and at discharge form hospital. French cardiologists have followed the recommendations of the large scale clinical trials published during this period. The improved hospital mortality corresponds to the beneficial results reported in trials with aspirin, betablockers, ACE inhibitors and thrombolytics.
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PMID:[Epidemiology according to the European and French scales of myocardial infarction. Data of the MONICA project]. 894 13


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