Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial interstitium plays an important role in the regulation of cardiac function compared with myocytes and it is actively involved in ischemia-reperfusion damage and in the acute and chronic remodelling during ischemic heart diseases. Myocardial post-ischemic oedema seems to interfere in this process. Myocardial oedema is able to induce structural alterations, to reduce myocardial function and to activate the renin-angiotensin-aldosterone system. Angiotensin II and aldosterone seem to be the cause of myocardial fibrosis that is detected during ischemic heart disease. Post-ischemic vascular permeability alterations have a similar role. In clinical conditions, ACE-inhibitors have important effects on cardioreparation and are able to improve cardiac function and reduce early and late mortality. The effects of myocardial oedema reduction (i.e. hypertonic reperfusion) on ischemia-reperfusion damage and myocardial fibrosis are still to clarify. A reduction in myocardial fibrosis may improve cardioreparation and prevent congestive heart failure, following ischemic heart disease.
 ...
PMID:[Role of interstitial myocardium in ischemia-reperfusion injury: experimental data and clinical implications]. 763

The role of calcium regarding the origin of irreversible impairment of the myocardial tissue is being intensively studied. An important role in this process is played by mitochondria which by means of the active Ca2+ uptake stimulate its oxidative metabolism and intervene into the Ca2+ homeostasis in mitochondrial cells. The study investigates the influence of cardioprotective substances with distinct mechanisms of the mitochondrial Ca2+ uptake effect. The experiments were performed on chinchilla buck rabbits of 2500-3000 g of body weight. Isolated hearts were perfused according to the method of Langendorff, ischemia was evoked by a 60-minute stoppage of the coronary blood flow. The cardioprotective substances were added into the perfusion solution prior to ischemia inducement. We investigated the following cardioprotective substances: Spirapril (ACE inhibitor), magnesium (Mg2+), and MDL 73,404 (antioxidant, synthetic analogue of alpha-tocopherol). After the 60-minute ischemy the mitochondrial Ca2+ uptake decreased by 43% in comparison with the control group (p < 0.01), Spirapril caused its accretion by 35% in comparison with the ischemic group (p < 0.05), and magnesium increased the uptake even by 52% (p < 0.001). The MDL 73,404 substance had no effect on the mitochondrial Ca2+ uptake. On the basis of experimental results we assume that the cardioprotective effects of Spirapril and magnesium can be besides other factors intermediated also by the increase of intramitochondrial enzymatic activity in consequence of augmented transport of Ca2+ into mitochondria. The cardioprotective effect of the MDL 73,404 substance is assumedly caused by its antioxidant properties. (Fig. 4, Ref. 21.)
 ...
PMID:[Significance of mitochondrial Ca2+ transport in ischemic injury and myocardial protection]. 781 44

ACE inhibitors induce an increase in kinin levels with subsequent release of nitric oxide (NO) and prostacyclin, as shown in cultured endothelial cells and isolated rat hearts. Isolated perfused working rat hearts continuously release kinins and prostacyclin. During ischemia after ligation of the left coronary artery kinin and prostacyclin concentrations in the venous effluent of the hearts are increased. ACE inhibition with ramiprilat increases kinin concentrations during normoxia, ischemia and reperfusion, whereas deendothelialization markedly reduces kinin and prostacyclin outflow in controls as well as in ACE inhibitor-treated hearts. Rat hearts with postischemic reperfusion arrhythmias are protected by ramiprilat- and bradykinin perfusion, cardiodynamics and metabolism of treated hearts are improved. These effects are observed in concentrations too low to increase coronary flow. The cardioprotective effects of ramiprilat and bradykinin are abolished by the specific B2-kinin receptor antagonist icatibant and by an inhibitor of NO-synthase. Long-term treatment (20 weeks) with ramipril in a blood-pressure-lowering dose (1 mg/kg/day) and a subantihypertensive dose (10 micromg/kg/day) protects spontaneously hypertensive rats (stroke prone) against hypertension and left ventricular hypertrophy in the high dose. In addition, both treatment regimens induce myocardial capillary growth. Isolated hearts of these animals show increased myocardial contractility and coronary flow, reduced release of cytosolic enzymes into the coronary effluent, and improved myocardial metabolism. These changes are observed even at a dose of ramipril which does not affect blood pressure and left ventricular hypertrophy. They are abolished by chronic blockade of kinin receptors with icatibant.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Cardioprotective effects by ramipril after ischemia and reperfusion in animal experiment studies]. 785 80

Based on the foregoing data it is not unreasonable to hypothesize that restoration of flow in the infarct-related artery at a later date might decrease mortality. If that is the case, then a strong argument can be made for coronary angiography in patients surviving acute myocardial infarction. Of course, the ideal way to investigate this problem is to perform a large-scale prospective trial in which patients who have an occluded infarct-related artery are randomized to a revascularization procedure or continued on nonsurgical therapy. The specific management strategy for the patient with an occluded infarct-related artery after myocardial infarction depends on several features that the patient exhibits. For example, the presence or absence of LV dilatation, arrhythmias, recurrent ischemia, or clinical heart failure may dictate one form of therapy or another. There is no generic postinfarction patient with an infarct-related artery occlusion. Choices of drugs to use in these patients include the vasodilators, such as nitrates and ACE inhibitors, as well as aspirin and beta blockers. The use of calcium antagonists, chronic anticoagulants, and antiarrhythmics should have specific indications. Antithrombin agents are still experimental.
 ...
PMID:Management of myocardial infarction patients with an occluded infarct-related artery. 791 May 40

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium ischemia is still ongoing, whereas in stunned myocardium blood flow is fully or almost fully restored. Both the hibernating and the stunned myocardium retain an inotropic reserve. In hibernating myocardium the increase in contractile function is at the expense of metabolic recovery whereas in stunned myocardium no metabolic deterioration occurs during inotropic stimulation. Therefore, inotropic stimulation in combination with metabolic imaging may help not only to identify viable, dysfunction myocardium but also to distinguish hibernating and stunned myocardium. The only causal therapy of hibernating myocardium is to restore blood flow to the hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since by definition blood flow is normal and contractile function will recover spontaneously. If, however, myocardial stunning involves large parts of the left ventricle and thus impairs global left ventricular function, the extent of myocardial stunning can be reduced by inotropic stimulation, without inducing further damage to the myocardium. In the experimental setting, antioxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, most effectively when administered before ischemia.
 ...
PMID:Characterization of hibernating and stunned myocardium. 795 33

The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation and increase prostacyclin and bradykinin levels. In the chronic phase remodelling may be attenuated. At present, a large number of controlled clinical trials mainly focussing on the effects of ACE-inhibition in the chronic phase is under way. Only few studies concentrate on the effect of acute intervention with ACE-inhibitors in ischemia-reperfusion i.e. thrombolysis in myocardial infarction. In the Captopril And Thrombolysis pilot study (CAT pilot-study) 3 mg and 6.25 mg captopril was tolerated well as adjunctive therapy to intravenous streptokinase. Decrease in mean arterial blood pressure (36 +/- 11%) after 6.25 mg was comparable to the control group (30 +/- 7%). Furthermore noradrenaline levels decreased dose dependently to 47 +/- 6 and 38 +/- 7% from baseline respectively. These results prompted a large nationwide acute intervention trial with captopril in 300 patients receiving thrombolytic therapy: the Captopril And Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of converting enzyme inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring and neurohumoral measurements immediately upon thrombolysis and during the first year after myocardial infarction. Blinded data show a favourable blood pressure response, with systolic hypotension below 100 mm Hg occurring only in 0.2% of patients.
 ...
PMID:Angiotensin-converting enzyme inhibition during thrombolytic therapy in acute myocardial infarction: the Captopril and Thrombolysis Study (CATS). 812 21

Enhanced formation of radicals during post-ischemic reperfusion, foremost of superoxide (O2-) and hydroxyl (OH) radicals, has been directly and indirectly demonstrated in a number of tissues. However, the close chemical interrelationship of O2- and OH with other non-radical oxidants, such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), makes it prudent to speak of reactive oxygen metabolites in conjunction with cell and organ dysfunction incurred by reperfusion. In the case of the heart, evidence for the causal involvement of such reactive molecular species includes (1) the increased formation of lipid peroxides, (2) the ability to mimic all facets of reperfusion injury (arrhythmias, contractile and vascular dysfunction, infarct extension) by exogenously applying reactive oxygen species, and (3) the propensity of a great variety of antioxidative and radical scavenging measures to afford cardioprotection during reperfusion. Potential sources of reactive oxygen metabolites in the reperfused heart are the mitochondrial redox-chain, endothelial enzymes such as cyclooxygenase, monoaminooxidase, NO-synthase and xanthine oxidase, and formed blood constituents (platelets, monocytes, granulocytes). According to our own results, adenosine, endogenously formed in the heart during ischemia, rapidly enhances adhesion of granulocytes introduced into the coronary system at reperfusion. Furthermore, small numbers of these cells suffice to induce contractile dysfunction in an isolated guinea pig heart model of ischemia-reperfusion injury, the major mediator of damage being HOCl. The striking disparity between the enormous volume of experimental data supporting involvement of reactive oxygen metabolites in reperfusion damage and the virtual lack of clinical-therapeutic regimens employing anti-oxidative measures is largely due to a still rudimentary knowledge of the homeostatic control of formation and removal of radicals and oxidants. In particular, the inability to correctly assess the individual time-course and extent of oxidative stress seems to be a major problem. Also, confounding issues such as compartmentation of radical formation as opposed to radical scavenging and the unwitting down-regulation of endogenous protective systems (e.g., of uric acid in the course of inhibiting xanthine oxidase) need to be resolved. On the other hand, we have been able to demonstrate protection by ACE inhibitors elicited via endothelially produced nitric oxide (a scavenger of O2- and OH) in the isolated heart. Thus, enhancement of endogenous protection may offer a perspective for mitigating against reperfusion damage.
 ...
PMID:[Possible significance of free oxygen radicals for reperfusion injury]. 815 62

Necrosis of the femoral head and osteopenia were examined histopathologically in stroke-prone spontaneously hypertensive rats (SHRSPs) aged 6 to 36 weeks and compared with that of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs). Avascular necrosis of the femoral head was frequently observed, mainly in the young SHRSPs and SHRs (about 8 to 15 weeks of age). SHRSPs had the highest incidence of femoral head necrosis among the three strains. This necrotic change in the femoral head was considered to be secondary ischemia induced by angiospasm or arteriosclerosis, similar to the disorders observed in the brain, kidney, and heart in SHRSPs. However, the complication occurred in spite of treatment with antihypertensive agents (ACE inhibitor: enalapril, spirapril) even though other ischemic disorders such as brain hemorrhage and renal infarction were prevented, indicating that the femoral head necrosis in SHRSPs was not due to hypertensive complications induced by angiospasm or arteriosclerosis. Bone mineral density (BMD) of the femoral bone was significantly lower in SHRSPs, and the femoral heads in this strain were the most easily deformed by loads applied during compression tests. Histopathologically, the infarctions were encountered on the lateral side of the epiphysis, but no thrombi were observed. The lateral side of the epiphysis is the anatomic site where the weight load is greatest and the site where the nutritive artery enters. Our results strongly suggest that the coexistence of vulnerable bone matrix and physical weight load to the nutritive artery plays a crucial role in the occurrence of femoral head necrosis in SHRSPs, whether based on generalized or localized osteopenia.
 ...
PMID:Femoral head necrosis and osteopenia in stroke-prone spontaneously hypertensive rats (SHRSPs). 826 49

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.
 ...
PMID:Effect of angiotensin-converting enzyme inhibitors on myocardial ischemia/reperfusion injury: an overview. 835 31

Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris-symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine to what extent under clinical conditions coronary flow reserve can be improved, in hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (Dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with the ACE-inhibitor enalapril (10-20 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, the coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a decrease in LV muscle mass by about 8%, coronary reserve was improved after enalapril by 48%. It is likely that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities at the level of the coronary microcirculation. Consequently, it seems that reparation of hypertensive remodeling of the coronary microcirculation can be induced by ACE-inhibitor therapy.
 ...
PMID:ACE-inhibitors and coronary microcirculation. 835 38


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