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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme (ACE) inhibitors have become the cornerstone of therapy for congestive heart failure (CHF). Because ischemic heart disease is the most common cause of CHF, aspirin is frequently given concomitantly with ACE inhibitors in patients with CHF. Increased bradykinin levels, with the consequent enhanced synthesis of vasodilatory prostaglandins, appear to mediate a significant benefit of ACE inhibitor therapy in these patients. In contrast, aspirin inhibits cyclooxygenase, and thereby suppresses prostaglandin production. Thus, these counteracting effects on prostaglandins may result in antagonism between ACE inhibitor and aspirin therapy in heart failure patients. Several early reports questioned the safety of aspirin in CHF, and the potential antagonistic interaction between ACE inhibitors and aspirin in patients with heart failure has become the focus of both increasing research and intense debate. This article briefly highlights the theoretic considerations underlying this interaction, and reviews the available evidence for such an interaction from clinical trials.
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PMID:The angiotensin-converting enzyme inhibitor and aspirin interaction in congestive heart failure: fear or reality? 1130 80

This report reviews the author's involvement in the growth of ideas and basic concepts in myocardial ischemia resulting in the histological changes of myocardial infarction. Concepts arising from the study of myocardial substrate utilization, activation of the inducible form of nitric oxide synthase and production of prostacyclin and thromboxane in the infarcted heart are presented. New approaches are discussed dealing with the effects of nonsteroidal anti-inflammatory drugs on myocardial production of nitric oxide and prostanoids, and with the relevance of the inducible form of cyclooxygenase. The review also records a number of significant similarities between angiogenesis in the ischemic heart and some cancers. Angiogenesis in both instances originates from inflammatory reactions, illustrating how different tissues and organs such as ischemic heart muscle and cancer react to similar pathological stimuli in an identical manner. This multifocal approach opens new concepts on myocardial ischemia and cancer.
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PMID:Myocardial ischemia and infarction: growth of ideas. 1139 43

This review presents a comprehensive discussion on the chemistry, pharmacokinetics, and pharmacodynamics of ifetroban sodium, a new thomboxane A2/prostaglandin H2 receptor antagonist. Thromboxane A2 is an arachidonic acid product, formed by the enzyme cyclooxygenase. In contrast to other cyclooxygenase products, thromboxane A2 has been shown to be involved in vascular contraction and has been implicated in platelet activation. In general, results of clinical studies and animal experiments indicate that hypertension is associated with hyperaggregability of platelets and increased thomboxane A2 levels in blood, urine, and tissues. The precursors to thromboxane A2, prostaglandin G2, and prostaglandin H2, also bind and activate the same receptors. Thus, a receptor antagonist was thought to be an improved strategy for reversing the actions of thromboxane A2/prostaglandin H2, rather than a thromboxane synthesis inhibitor. This review describes new methods for the synthesis and analysis of ifetroban, its tissue distribution, and its actions in a variety of animal models and disease states. We describe studies on the mechanisms of how ifetroban relaxes experimentally contracted isolated vascular tissue, and on the effects of ifetroban on myocardial ischemia, hypertension, stroke, thrombosis, and its effects on platelets. These experiments were conducted on several animal models, including dog, ferret, and rat, as well as on humans. Clinical studies are also described. These investigations show that ifetroban sodium is effective at reversing the effects of thromboxane A2- and prostaglandin H2-mediated processes.
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PMID:Ifetroban sodium: an effective TxA2/PGH2 receptor antagonist. 1148 65

There is increasing evidence that cyclooxygenase (COX)-2 possess both angiogenic and cardioprotective properties. We examined the effects of hypoxic cardiac myocytes (H9c2 cells) on COX-2 expression in human umbilical vein endothelial cells (HUVECs) to determine the pathway involved in COX-2 regulation. The medium from hypoxic (<1% O2) cardiac myocytes (HMCM) or normoxic cardiac myocytes (21% O2) was added to HUVEC cultures. HMCM induced a transient increase of COX-2 mRNA expression at 1 and 3 h without affecting the COX-1 mRNA level. A similar effect also observed in HMCM from cultured primary cardiac myocytes (rat neonatal cardiac myocytes). The increased COX-2 mRNA was associated with a time-dependent increase in COX-2 protein expression. COX-2 was significantly induced by VEGF (4.86 +/- 1.03-fold) and IL-1beta (3.93 +/- 0.89-fold) and slightly increased by TNF-alpha but not by FGF2, IGF-1, or PDGFs. Analysis of proteins secreted in HMCM showed increased levels of VEGF but not IL-1 beta or TNF-alpha. The HMCM-induced COX-2 expression was inhibited by the addition of an anti-VEGF neutralizing antibody. VEGF induced endothelial cell COX-2 expression by both increasing COX-2 transcription and prolonging the COX-2 mRNA half-life. Furthermore, staurosporine, a nonselective PKC inhibitor, prevented the induction of VEGF by hypoxia. Both a selective PKC-alpha and -beta inhibitor and an inducible nitric oxide synthase (NOS) inhibitor decreased the induction of COX-2 by HMCM and VEGF. Finally, HMCM-induced upregulation of COX-2 was accompanied by upregulation of PGI2 and PGE2. These results suggest that VEGF is one of the principal factors produced by hypoxic myocytes that is responsible for the induction of endothelial cell COX-2 expression. This process likely involves both PKC and NOS pathways. Our findings have important implications regarding the cardiac protection of COX-2 in ischemic heart disease.
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PMID:Hypoxia induces myocyte-dependent COX-2 regulation in endothelial cells: role of VEGF. 1288 Dec 20

A steadily increasing number of investigations demonstrate that preconditioning with volatile anesthetics attenuates the deleterious effects of myocardial ischemia and reperfusion injury by an ischemic preconditioning-like mechanism. Thus volatile anesthetics may represent the best choice for anesthesia of patients at risk for myocardial ischemia. However, factors such as old age, coexisting conditions such as diabetes mellitus and the use of oral hypoglycemic drugs or cyclooxygenase inhibitors, timing and duration of myocardial ischemia, and possible constraints of a complicated preconditioning protocol may limit the benefits of this powerful tool under clinical conditions. The purpose of this minireview is to provide a brief overview of the results of basic and clinical research on cardioprotection by volatile anesthetics.
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PMID:Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside? 1507 68

The two cyclooxygenase isoforms (COX-1 and COX-2--coxibs) have overlapping functions and both are involved in the regulation of homeostatic and inflammatory processes in the various tissues. Treatment with highly selective COX-2 inhibitors is associated with significantly fewer serious adverse gastrointestinal events than is treatment with the dual inhibitors--the non-selective NSAIDs. Of the two coxibs, rofecoxib was shown to be much more selective than celecoxib and with less interaction with other drugs. Various clinical studies have demonstrated that the coxibs are equivalent, in anti-inflammatory, analgesic and antipyretic efficacy to comparator non-selective NSAIDs in osteoarthritis, rheumatoid arthritis, post surgery pain and dysmenorrhea. Perioperative use of coxibs reduces pain, opioid consumption and the risk of bleeding caused by the non-selective NSAIDs. The coxibs show similar tolerability for renal, liver and cardiothrombotic events as compared to the non-selective NSAIDs. Coxibs are contraindicated in pregnancy, in nursing mothers and pediatric patients and should be used with caution in patients with asthma. The impact of the coxibs on the cardiovascular system is controversial. However, coxibs should be used in caution and at the lowest recommended dose in patients with hypertension, ischemic heart disease and heart failure. These drugs do not interfere with the aspirin anti-platelet aggregation activity. Emerging evidence suggest that the coxibs may also find potential use as supportive therapy in various malignant tumors and intestinal polyps where COX-2 is overly expressed.
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PMID:[Is there a future for COX-2 inhibitors?]. 1560 72

Reactive oxygen species (ROS), as superoxide and its metabolites, have important roles in vascular homeostasis as they are involved in various signaling processes. In many cardiovascular disease states, however, the release of ROS is increased. Uncontrolled ROS production leads to impaired endothelial function and consequently to vascular dysfunction. This review focuses on two clinical conditions associated with elevated ROS levels: ischemia/reperfusion and nitrate tolerance. Injury caused by ischemia/reperfusion is an important limitation of transplantations, and complicates the management of stroke and myocardial infarction. Nitrates, which are used to treat transient myocardial ischemia (angina pectoris), decrease in efficacy in long-term continuous administration. There are several enzyme systems, such as xanthine oxidase, cyclooxygenase, uncoupled endothelial nitric oxide synthase, NAD(P)H oxidase, cytochrome P450 and the mitochondrial electron transport chain, which are responsible for the increased vascular production of superoxide. The contribution of particular ROS producing enzymes and the effect of antioxidant treatment are discussed in both pathological conditions.
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PMID:Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. 1563 16

Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)-alpha expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-alpha production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-alpha production. Dominant negative AMP-activated protein kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF-alpha production. Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin E(2) in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-alpha production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.
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PMID:Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. 1621 Oct 35

For over 50 years, acetaminophen (paracetamol) has been a staple in industrialized and non-industrialized countries for the treatment of pain and fever. Although its precise mechanisms of action are not known, the drug generates dose-dependent reduction in circulating prostaglandins, inhibits myeloperoxidase and the oxidation of lipoproteins, and appears to confer cardioprotection by blocking the effects of hydroxyl radical, peroxynitrite, and hydrogen peroxide. The drug might inhibit cyclooxygenase, although its ultimate target(s) is (are) still unclear. Sadly, since most investigations of acetaminophen have focused on its analgesic/antipyretic properties and hepatotoxicity, the effects of the drug on other mammalian organ systems, including the heart and circulation, have been ignored. Recently, work in our laboratory has shown acetaminophen to have a protective role in the injured mammalian myocardium. The cardioprotection was first observed in isolated, perfused guinea pig hearts subjected to ischemia-reperfusion injury. Hearts pretreated with acetaminophen recovered greater ventricular function and exhibited improved myofibrillar ultrastructure when compared to vehicle-treated hearts. More recent in vitro investigations have suggested protective roles for acetaminophen in barbiturate-induced arrhythmogenesis and myocardial hypoxia-reoxygenation injury. We have also extended our work to the in vivo arena. There, we found that acetaminophen reduced infarct size in dogs exposed to 60 minutes regional myocardial ischemia and 180 minutes reperfusion. We invite and encourage readers of this review to repeat/duplicate our experiments. Such work is needed to either challenge or support our findings. Further, more clinically-relevant work depends on these basic and related translational experiments.
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PMID:An old drug with a new purpose: cardiovascular actions of acetaminophen (paracetamol). 1624 34

Nitric oxide (NO) and cyclooxygenase-derived prostaglandins, such as prostacyclin (PGI2), are involved in vascular homeostasis. To better understand the reciprocal role of both NO and PGI2 on myocardial infarction in the rat, we have investigated the cardioprotective effect of nitro-naproxen, isosorbide dinitrate (ISDN), L-arginine, defibrotide and naproxen. In this study, male Wistar rats were treated orally once a day for 5 consecutive days with the compounds under investigation and then, under anesthesia, the animals were subjected to acute myocardial ischemia (30 min) and reperfusion (120 min). Systemic blood pressure, left ventricular pressure and related parameters of cardiac mechanics were recorded. Ventricular arrhythmias and infarct size of the left ventricular wall were also evaluated. Furthermore, cardiac myeloperoxidase (MPO) and plasma creatine phosphokinase (CPK) activities were determined. Defibrotide, nitro-naproxen, ISDN and L-arginine all provided a cardioprotection characterized by significant prevention of arrhythmias with high survival rate of the rats. Infarct size restriction was paralleled by reduction of both cardiac MPO and plasma CK. Cardioprotection of nitro-naproxen, ISDN and L-arginine involve nitrites/nitrates and PGI2-increased in the circulation associated to a reduction of thromboxane B2 (TXB2) in the blood. Defibrotide displays a cardioprotection by increasing PGI2 release and by reducing TXB2 in the blood. Naproxen was devoid a lower protecting activity on myocardial infarction, and PGI2 inhibition may have played a critical role in this context. The results suggested that the increase of both NO and PGI2 brings about a cascade of integrated cellular and molecular events which are of paramount importance in prevention of myocardial ischemic insult.
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PMID:Nitric oxide and prostacyclin pathways: an integrated mechanism that limits myocardial infarction progression in anaesthetized rats. 1648 24


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