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

The predominant venodilator properties of the nitrates and their augmentation of collateral coronary blood flow to the ischemic myocardium endows them with some ideal characteristics for treating myocardial ischemic syndromes. Additional efficacy stems from the ability of the nitrates to replenish the deficient endothelium-derived relaxing factor (EDRF), nitric oxide (NO), in patients with coronary heart disease and also to inhibit platelet aggregation. In stable angina pectoris, the antianginal and antiischemic effects of oral nitrates are well established. Continuous administration of nitrates may lead to tolerance of their clinical efficacy. Recent studies, however, have demonstrated that when used in recommended doses, tolerance can be avoided during long-term treatment with oral nitrates without provocation of anginal attacks during periods of low nitrate levels at night and early hours of the morning. Thus, prolonged treatment with an asymmetric twice-daily regimen of immediate-release isosorbide-5-mononitrate in patients with stable angina pectoris does not give rise to clinical tolerance, prolongs exercise duration, and delays the onset of myocardial ischemia. In unstable angina pectoris, nitrates rapidly relieve chest pain and ameliorate the electrocardiographic signs of myocardial ischemia. In patients with acute myocardial infarction, early treatment with nitrates prevents left ventricular dilatation, improves pumping function, and reduces the risk of ventricular arrhythmias. In patients with chronic heart failure, oral nitrates improve exercise tolerance and, when given in combination with the systemic arterial dilator hydralazine, extend survival. Meta-analysis of published studies has demonstrated that both intravenous and oral nitrates reduced infarct size and morbidity and mortality in patients with acute myocardial infarction. In the ISIS 4 post-infarction study, isosorbide-5-mononitrate 60 mg once daily was not superior to placebo in reducing mortality risk. However, in the GISSI 3 study, the combination of nitrates with an angiotensin-converting enzyme (ACE) inhibitor reduced mortality risks by 17% in patients with acute myocardial infarction. In both the ISIS 4 and GISSI 3 studies, 62% and 57% of the patients in the placebo and control groups, respectively, were treated with nitrates for control of rest angina, myocardial ischemia, and or left ventricular failure symptoms, and this widespread use of open-label nitrates in the control groups may have diluted the true beneficial effects of nitrates in both studies. Taken together, these many studies with oral nitrate treatment in coronary heart disease and heart failure clearly emphasize that these drugs are safe and play more than a symptomatic role in the management of patients with acute and chronic ischemic syndromes due to coronary artery disease.
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PMID:Oral nitrates: more than symptomatic therapy in coronary artery disease? 921 Oct 13

L-Carnitine can affect cardiac function principally by improving fatty acid and/or glucose metabolism, by increasing perfusion due to modulation of the deformability of erythrocytes and/or vasodilatation, and by stabilising mitochondrial and plasma membranes of cardiomyocytes. While short-term administration of L-carnitine in vivo does not increase the muscular and probably also not the cardiac L-carnitine content, it improves the function of perfused rat or pig hearts in the reperfusion phase after ischemia. Long-term administration of L-carnitine increases the cardiac L-carnitine content in mice and has been shown to improve surrogate markers of coronary heart disease such as arrhythmias, nitrate consumption, and left ventricular dilatation and infarct size in patients after myocardial infarction. The only clear indication for L-carnitine in cardiology is to date cardiomyopathy associated with primary L-carnitine deficiency.
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PMID:[Physiologic bases for the use of L-carnitine in cardiology]. 952 39

Vasodilator therapy with nitrates has been used for almost a century to bring relief to patients suffering from angina. The acute anti-ischemic effects of nitro-vasodilators for the treatment and prevention of anginal attacks is unquestioned. In addition, nitrates are administered in order to reduce symptomatic and silent ischemic episodes, in patients with proven coronary heart disease who exert ST segment alterations on Holter monitoring. The reduction in total ischemic burden may result in an improved prognosis with regard to infarct prevention and possible prevention of deterioration of left ventricular function due to repetitive episodes of myocardial ischemia. In patients with unstable angina, administration of nitrates significantly diminishes ischemic episodes and reduces the number of clinically symptomatic anginal attacks. The prevention of left ventricular dilatation in patients within the first few days and months following acute myocardial infarction may be due to the reduced preload. In patients with heart failure, preload reduction with nitrates and afterload reduction with hydralazine was tested versus angiotensin converting enzyme (ACE) inhibitors. However, unfortunately, very few data are available concerning the combination therapy of ACE inhibitors and nitrates in heart failure and following acute myocardial infarction. Long-term continuous administration of high doses of nitrates may cause nitrate tolerance, thus reducing the vasodilator potency of these drugs. Since nitrates were introduced into medical therapy many decades before randomized controlled trials were performed, and evidence-based medicine became the basic principal for medical therapy, there are still indications and situations where the full therapeutic potential of nitrates is not being fully appreciated. During recent decades, other anti-ischemic drugs, i.e., beta-receptor agonists and calcium channel blockers, were introduced into the clinical setting and contributed to an optimized therapy for patients with coronary heart disease. Nevertheless, due to their proven and unsurmounted symptomatic efficacy, nitrates will remain one of the cornerstones of acute and long-term therapy of patients with coronary heart disease far beyond the year 2000.
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PMID:Role of nitrates for the therapy of coronary artery disease patients in the years beyond 2000. 1049 56

Reduced nitric oxide bioavailability contributes to progression of cardiac dysfunction and remodeling in ischemic heart failure. Clinical use of organic nitrates as nitric oxide donors is limited by development of nitrate tolerance and reactive oxygen species formation. We investigated the effects of long-term therapy with pentaerythritol tetranitrate (PETN), an organic nitrate devoid of tolerance, in rats with congestive heart failure after extensive myocardial infarction. Seven days after coronary artery ligation, rats were randomly allocated to treatment with PETN (80 mg/kg BID) or placebo for 9 weeks. Long-term PETN therapy prevented the progressive left ventricular dilatation and improved left ventricular contractile function and relaxation in rats with congestive heart failure. Mitochondrial superoxide anion production was markedly increased in the failing left ventricular myocardium and nearly normalized by PETN treatment. Gene set enrichment analysis revealed that PETN beneficially modulated the dysregulation of mitochondrial genes involved in energy metabolism, paralleled by prevention of uncoupling protein-3, thioredoxin-2, and superoxide dismutase-2 downregulation. Moreover, PETN provided a remarkable protective effect against reactive fibrosis in chronically failing hearts. Mechanistically, induction of heme oxygenase-1 by PETN prevented mitochondrial superoxide generation, NOX4 upregulation, and ensuing formation of extracellular matrix proteins in fibroblasts from failing hearts. In summary, PETN targeting reactive oxygen species generation prevented the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance. Therefore, PETN might be a promising therapeutic option in the treatment of ischemic heart diseases involving oxidative stress and impairment in nitric oxide bioactivity.
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PMID:Pentaerythritol Tetranitrate Targeting Myocardial Reactive Oxygen Species Production Improves Left Ventricular Remodeling and Function in Rats With Ischemic Heart Failure. 2635 Oct 29