Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During myocardial ischaemia, either in chronic coronary insufficiency or the acute phase of myocardial infarction, the renin-angiotensin system is activated which, by its deleterious cardiac effects, aggravates the ischaemia. Angiotensin Converting Enzyme (ACE) inhibitors, by their indirect effects (improved conditions of left ventricular load, negative inotropism, attenuation of catecholaminergic stimulation), reduce myocardial oxygen consumption, and by their direct coronary vasodilator effect reduce myocardial ischaemia. In addition, by attenuating the formation of oxygen-free radicals, by participating in the inactivation of some of them and protecting the lysosomal membranes, they combat reperfusion injury. In the animal model of acute myocardial infarction, they reduce myocardial infarct size and the prevalence of reperfusion arrhythmias. In the clinical situation, their effects on the ischemic response to effort in anginal patients remain controversial, appear to be more marked in abnormalities of the coronary micro-circulation especially in syndrome X and in hypertensive heart disease. In ischemic heart disease, long-term treatment may be beneficial by their trophic coronary and myocardial effects and two large scale trials report a decrease in the recurrence of myocardial infarction with ACE inhibitors. In the acute phase of myocardial infarction if their possible actions on reducing the infarct size and reperfusion arrhythmias require further confirmation, they do limit expansion of the infarct and decrease early left ventricular dilatation. However, the appreciation of tolerance is variable and the timing of their introduction remains controversial.
 ...
PMID:[Action of converting enzyme inhibitors on myocardial ischemia and reperfusion injuries]. 830 19

The success of angiotensin-converting enzyme (ACE) inhibitors in reducing cardiovascular morbidity and mortality rates has led to a reexamination of the role of the renin-angiotensin system in pathophysiology. Ventricular dysfunction leading to congestive cardiac failure is associated with sequential activation of the sympathetic system and increases in plasma atrial natriuretic peptide; however, increases in plasma renin and aldosterone do not occur until very late. The renin-angiotensin system is now regarded as both a circulating and tissue hormonal system. All components of the renin-angiotensin system have been detected in the heart. ACE is localized in discrete areas of the heart, including the cardiac valves, coronary vessels, atria, and myocardium. After experimental myocardial infarction in the rat, although plasma renin and aldosterone levels are not increased, ACE in the myocardium is markedly increased. Treatment with ACE inhibitors suppresses cardiac ACE and is associated with hemodynamic improvement, reversal of the neurohumoral activation, prevention of ventricular dilatation, and remodeling and reduction in mortality rates. These results suggest that the beneficial effects of ACE inhibitors in treating congestive cardiac failure, preventing ventricular remodeling, and regressing left ventricular hypertrophy may involve not only reducing preload and afterload but also suppressing the local cardiac renin-angiotensin system.
 ...
PMID:The cardiac renin-angiotensin system in heart failure. 836 49

Chronic heart failure is a disabling and lethal disorder with high incidence and prevalence in Western societies. Treatment with angiotensin-converting enzyme (ACE) inhibitors and heart transplantations diminish both mortality and morbidity, although both still remain high. Increased understanding of some of the pathophysiologic mechanisms involved in the development of left ventricular dysfunction and the transition from asymptomatic systolic dysfunction to symptomatic heart failure has opened gates to new dimensions for the treatment of this disorder. The initial event in the pathophysiologic process is damage to the myocardium, most frequently a myocardial infarction. Almost simultaneously, activation of different neurohormonal systems occurs. The renin-angiotensin system and sympathetic nervous system are activated. Increased concentrations of hormones with counteractive activity have also been found, such as ANP and BNP. Interestingly, prolonged neurohormonal activation seems to occur only in patients with large infarcts or in patients with poor systolic function of the left ventricle. Moreover, available data from an echocardiographic study indicates that in patients with high concentrations of neurohormones in plasma a week after their infarction, left ventricular dilatation and systolic dysfunction of the left ventricle are highly likely to develop during long-term follow-up. Several studies have showed that ACE inhibitors are efficacious in chronic heart failure and among patients with reduced ejection fraction after myocardial infarction. What these patients have in common is prolonged neurohormonal activation, which theoretically may be harmful to myocardial cell structure and function. ACE inhibitors reduce the breakdown of angiotensin I to angiotensin II and increase the concentration of circulating bradykinins and prostaglandins. Further modulation of neurohormonal activity might be beneficial. Therefore, future treatment of chronic heart failure or asymptomatic left ventricular dysfunction might include beta-adrenergic blockers, neutral endopeptidase inhibitors, ANP, BNP, angiotensin II receptor antagonists, and modulators of sympathetic activity.
 ...
PMID:The role of neurohormonal activation in chronic heart failure and postmyocardial infarction. 867 61

Spontaneously hypertensive rats (SHR) of advanced age exhibit depressed myocardial contractile function and ventricular fibrosis, as stable compensated hypertrophy progresses to heart failure. Transition to heart failure in SHR aged 18-24 months was characterized by impaired left ventricular (LV) function, ventricular dilatation, and reduced ejection fraction without an increase in LV mass. Studies of papillary muscles from SHR with failing hearts (SHR-F), SHR without failure (SHR-NF), and age-matched Wistar Kyoto (WKY) rats allowed examination of changes in the mechanical properties of myocardium during the transition to heart failure. Papillary muscles of SHR-F exhibited increased fibrosis, impaired contraction, and decreased myocyte fractional area. These findings in papillary muscles were correlated with a higher concentration of hydroxyproline and increased histological evidence of fibrosis in the LV free wall. While a depression in active tension accompanied these structural alterations in papillary muscles, it was not evident when active tension was normalized to myocyte fractional area. Together, these data suggest that individual myocyte function may be preserved but that myocyte loss and replacement by extracellular matrix contribute substantially to the decrement in active tension. An absent or negative inotropic response to isoproterenol is observed in SHR-F and SHR-NF papillary muscles and may result in part from age-related alterations in beta-adrenergic receptor dynamics and a shift from alpha- to beta-myosin heavy chain (MHC) protein. During the transition to failure, ventricles of SHR exhibit a marked increase in collagen and fibronectin mRNA levels, suggesting that an increase in the expression of specific extracellular matrix genes may contribute to fibrosis, tissue stiffness, and impaired function. Transforming growth factor-beta 1 (TGF-beta 1) mRNA levels also increase in SHR-F, consistent with the concept that TGF-beta 1 plays a key regulatory role in remodelling of the extracellular matrix gene during the transition to failure. The renin-angiotensin-aldosterone system is also implicated in the transition to failure: SHR treated with the angiotensin converting enzyme inhibitor captopril starting at 12 months of age did not develop heart failure during the 18-24 month observation period. Captopril treatment that was initiated after rats were identified with evidence of failure led to a reappearance of alpha-MHC mRNA but did not improve papillary muscle function. Research opportunities include investigation of apoptosis as a mechanism of cell loss, delineation of the regulatory roles of TGF-beta 1 and the renin-angiotensin-aldosterone system in matrix accumulation, and studies of proteinase cascades that regulate matrix remodelling.
 ...
PMID:The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure. 868 57

The renin-angiotensin and adrenergic nervous systems are cross-regulated compensatory mechanisms that are induced or activated in the failing heart. In ventricular myocardium, the activation of one of these systems leads to activation or induction of the other, resulting in co-amplification of cellular mechanisms that result in cardiac myocyte hypertrophy, hyperplasia of nonmyocytic tissue components, increased contractility and heart rate, and increased ventricular volume. Although these changes serve to stabilize stroke volume and cardiac output following an insult to the myocardium, the chronic and continual activation of these systems produces ventricular dilatation and deleterious remodelling at a chamber level and progressive myocyte dysfunction at a cellular level. Because these systems are cross-regulated, inhibition of one of them attenuates the activity of the other. This appears to be especially true in the failing heart, where angiotensin converting enzyme inhibitors can produce substantial anti-adrenergic effects in individuals with high levels of adrenergic activation. The anti-adrenergic properties of angiotensin converting enzyme inhibitors may be at least partially responsible for the salutary effects of these agents in the clinical setting of heart failure or ischaemic heart disease.
 ...
PMID:Anti-adrenergic effects of angiotensin converting enzyme inhibitors. 886 34

Coronary heart disease is a multifactorial disease, influenced by environmental and genetic factors. Experimental and clinical data show that the renin-angiotensin system has important indications in coronary artery disease by influencing progressive ventricular dilatation, ventricular function, and outcome. Angiotensin II may have direct toxic effects on myocardial cells, induce hypertrophy in noninfarcted areas, activate the sympathetic nervous system, stimulate fibroblast proliferation, vasoconstrict coronary vessels, increase left ventricular afterload, and impair diastolic relaxation. Associations between a polymorphism of the angiotensinogen gene and angiotensin-converting enzyme gene and the occurrence of myocardial infarction have been reported. Patients with the DD genotype (ACE gene) have higher plasma ACE and myocardial ACE activity. Preliminary data suggest that the DD genotype is associated with more progressive ventricular dilatation post myocardial infarction and with a greater response after ACE inhibition. The DD genotype is also associated with a higher incidence of left ventricular hypertrophy, which may have implications for the induction of hypertrophy in noninfarcted areas. Whatever the mechanisms, chronic ACE inhibition, started early after myocardial infarction, improves survival and reduces mortality and morbidity for major cardiovascular events.
 ...
PMID:Role of the renin-angiotensin system as a risk factor for control of morbidity and mortality in coronary artery disease. 911 54

The multiple mechanisms that bring about the decompensation of the hypertrophic remodeled myocardium are synergistic and not fully understood. Our current hypothesis is that the increased stress on the ventricle is initially offset by compensatory myocardial hypertrophy. In many instances, however, progressive ventricular dilatation and heart failure occur as a result of maladaptive hypertrophy (abnormal myosin-actin production), programmed cell death (apoptosis) and/or changes in the interstitial vasculature and collagen composition. The molecular and genetic background to these processes includes changes in myocardial gene expression, activation of the local tissue renin-angiotensin and other neurohormonal systems, increased matrix metalloproteinase activity (including collagenase), and expression of certain components of the immune system, such as TNF-alpha. Future research will hopefully provide better methods for limiting the remodeling-ventricular dilatation process by novel pharmacotherapies, gene therapy and, possibly, surgical therapy, and determine the impact of such interventions on survival.
 ...
PMID:Ventricular remodeling: from bedside to molecule. 933 Jul 35

Angiotensin-converting enzyme (ACE) inhibitors are now established drugs in the treatment of hypertension and heart failure. The renin-angiotensin-aldosterone system is complex and acts as a circulating hormonal system, a local endogenous tissue system and neuromodular. Current experimental evidence suggests that ACE inhibitors reduce the risk associated with atherosclerotic cardiovascular disease. The antiatherogenic action of ACE inhibitors is related to complex effects mediated by these agent, including an antiproliferative and antimitotic action, beneficial effects on endothelial function, plaque-stabilizing effects and the action of these agents on the sympathetic nervous system. The role of ACE inhibitors in preventing the clinical sequale of atherosclerotic cardiac disease has been evaluated in various patient populations. Several small trial assess the effects of ACE inhibitors in severity of angina pectoris have reported conflicting results, with benefit is some patients and no benefit or even exacerbation of angina in others, indicating that ACE inhibitors do not have consistent antianginal effects in short-term study. ACE inhibitors have the theoretical potential to prevent restenosis after PTCA but they do not prevent restenosis and has no effect on overall clinical outcome. New data suggest that ACE inhibitors may be effective therapy fir patients following acute myocardial infarction. The renin-angiotensin system, is activated during new myocardial infarction and has an impact on the process of remodeling of the left ventricle which causes ist dysfunction and heart failure. In most of the large mortality trials the rationale for early treatment with ACE inhibitors after myocardial infarction was stated. ACE inhibitors have a positive effect in preventing the ventricular dilatation and they reduce the rate of reinfarctions and the mortality rate.
 ...
PMID:[The significance of converting enzyme inhibitor angiotensin I to angiotensin II in treatment of patients with coronary disease]. 955 7

Left ventricular (LV) dilatation after myocardial infarction (MI) is a major predictor of prognosis and identifies which patients will develop heart failure. Left ventricular dilatation or remodeling starts immediately after MI and progresses in the chronic phase of heart failure. Factors influencing remodeling, such as infarct size and neurohumoral activation, including the sympathetic and renin-angiotensin system, are discussed. Remodeling can be affected by reduction of infarct size and inhibition of neurohumoral activation. The effect of thrombolysis, beta-blockade, and angiotensin-converting enzyme (ACE) inhibition in the acute phase after MI and in the chronic phase of heart failure on remodeling are discussed. On the basis of beneficial effects of ACE inhibition and beta-blockade in acute MI and in chronic heart failure, a treatment strategy is proposed in which both ACE inhibition and beta-blockade are started early after MI. Depending on infarct size and ventricular function, continued treatment in the chronic phase of heart failure must be considered.
 ...
PMID:Left ventricular dilatation after myocardial infarction: ACE inhibitors, beta-blockers, or both? 973 89

The renin-angiotensin system is activated during myocardial ischemia, and local angiotensin II formation occurs in ischemic hearts. At least two angiotensin II receptor subtypes, the AT1 and AT2 receptor, have been identified. The cardiovascular effects of angiotensin II have been largely attributed to activation of AT1 receptors. In ventricular preparations from normal rat and pig hearts, the density of AT1 receptors is higher than that of AT2 receptors, whereas data on the AT receptor subtype density and its distribution in human hearts remain controversial. AT1 receptor blockade increases coronary blood flow during ischemia in dogs and during reperfusion in rats. It also reduces the incidence of ischemia-related arrhythmias in rats and guinea pigs, limits infarct size in pigs, improves functional and metabolic recovery following myocardial ischemia, and attenuates ventricular remodelling post-myocardial infarction in rats. The potential mechanisms responsible for the cardioprotection by AT1 receptor blockade remain to be elucidated in detail, but appear to involve AT2 receptor activation and the subsequent action of bradykinin, prostaglandins, and/or nitric oxide. Patients under treatment with AT1 receptor antagonists for indications such as hypertension and ventricular dilatation after myocardial infarction are likely to have improved prognosis when suffering an acute myocardial infarction.
 ...
PMID:AT1 receptor blockade in experimental myocardial ischemia/reperfusion. 983 69


<< Previous 1 2 3 Next >>