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

1. Functional and antiischaemic effects of monoacetyl-vitexinrhamnoside (AVR), a flavonoid with phosphodiesterase (PDE)-inhibitory properties contained in Crataegus species (Hawthorn, Rosaceae) were studied in several in-vitro models. 2. In rabbit isolated femoral artery rings, AVR concentration-dependently reduced developed tension. Vasodilation by AVR was reduced after inhibiting EDRF formation by L-NG-nitro arginine. 3. In spontaneously-beating Langendorff-guinea pig hearts, AVR concentration-dependently enhanced heart-rate, contractility, lusitropy and coronary flow. 4. In isolated electrically-driven Langendorff-rabbit hearts, acute regional ischemia (MI) was induced by coronary artery occlusion and quantified from epicardial NADH-fluorescence photography. AVR (5 x 10(-5) mol/l) induced a slight numerical increase of left ventricular pressure and coronary flow (p > 0.05). MI was reduced (p < 0.05). 5. Monoacetyl-vitexinrhamnoside is an inodilator whose vasodilatory action may be mediated in part by EDRF in addition to PDE-inhibition. Monoacetyl-vitexinrhamnoside does possess marked antiischemic properties even in isolated hearts, suggesting an improvement of myocardial perfusion.
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PMID:Functional and antiischaemic effects of Monoacetyl-vitexinrhamnoside in different in vitro models. 869 Feb 47

Several authors have alluded to the possible involvement of EDRF (NO) in ischemia-induced coronary artery dilation. Alternatively, it has been suggested that opening of ATP-dependent K channels could play a key role in this context. We studied the effects of sulfonylureas and NG-nitro-L-arginine (LNNA), a specific inhibitor of endothelial NO (EDRF) synthesis, on ischemia-induced coronary vasodilation in isolated Langendorff-perfused guinea pig hearts arrested with 15 mM KCl in normal Tyrode, and isolated pig coronary arteries precontracted with 43 mM KCl. In Isolated Langerdorff-perfused guinea pig heart, when hypoxia was simulated by switching 100% O2 in the perfusate to 100% N2, coronary perfusion pressure (CPP) fell from 90 cm H2O by 45 +/- 5 cm H2O. In the presence of LNNA, a specific inhibitor of NO synthetase in endothelial cells, CPP dropped by 44 +/- 6 cm H2O (n = 6; +/- SEM, no statistically significant). On biochemical simulation of ischemia (addition of iodoacetate [IAA]), CPP dropped 40 +/- 6 cm H2O, and in experiments performed under the same conditions but in the presence of LNNA, CPP dropped by 38 +/- 5 cm H2O (n = 6; +/- SEM; not statistically significant). When ischemia was simulated metabolically by equimolar replacement of 10 mM glucose with 2-deoxyglucose (DOG), an inhibitor of glycolysis CPP decreased by 24 +/- 1 cm H2O (n = 6; +/- SEM) after 15 minutes. This fall in CPP was almost prevented by 20 microM glibenclamide, whereas in the presence of 20 microM LNNA the DOG-induced decrease in CPP was not significantly inhibited, and CPP decreased by 22 +/- 2.6 cm H2O (n = 6; +/- SEM). In isolated pig coronary artery rings, maximal tension, achieved by depolarizing the smooth muscle cells by 43 mM KCl, decreased by 37 +/- 7% upon simulated hypoxia by replacing 100% O2 with 100% N2 in the perfusate (n = 6; +/- SEM) in arteries with intact endothelium. In arteries without endothelium, maximal tension also dropped by 35 +/- 6% (not statistically significant). In the same experiments the decrease in tension could be largely inhibited in the presence of 50 microM glibenclamide. Our results clearly show that in isolated perfused guinea pig hearts, as well as in isolated pig coronary arteries, EDRF does not play a decisive role in the coronary dilatory response to hypoxia and ischemia.
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PMID:EDRF does not mediate coronary vasodilation secondary to simulated ischemia: a study on KATP channels and N omega-nitro-L-arginine on coronary perfusion pressure in isolated Langendorff-perfused guinea-pig hearts. 978 7

Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance.
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PMID:[Transition of myocardial ischemia to heart failure]. 981 48

The most severe stages of arteriopathy often involve multifocal macrovascular lesions leading to defective perfusion of the distal tissues and subsequent dysfunction of the microcirculation. Diabetic autonomous neuropathy facilitates and aggravates this endothelial dysfunction. Loss of vasomotricity, platelet and white cell activation, and cytokine release lead to an obstruction of the capillaries and alteration or even destruction of the endothelium. At this stage, the lesions are irreversible and tissue vitality is definitively compromised. The goal of medical treatment is to delay the development of dysfunction and subsequent destruction of the microcirculation before, during and after restoration of sufficient flow through the macrocirculation lesions by angioplasty and/or surgery. Extrapolating from in vitro and animal studies, two mediators, EDRF (NO) and prostacycline, could theoretically inactivate inappropriate activated cells and re-establish flow. Besides their vasodilator proprieties, NO and prostacycline have a synergetic inhibitory effect on platelet and leukocyte activation. The role of platelet antiaggregates and heparins in this stage of severe chronic ischemia remains to be determined. The relative failures of therapeutic drug trials conducted since the end of the eighties demonstrates the importance of intervening before the microcirulation disorders become too severe. Until new compounds are developed, therapeutic progress can be achieved by more precise and earlier detection of alterations in the microcirculation to enable optimal management of arteriopathy of the lower limbs with surgery or angioplasty.
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PMID:[Diabetic arteriopathy. Microcirculation, an inevitable therapeutic objective]. 1131 21

The success of a free microvascular tissue transfer is based on a sufficient microanastomosis which meets the following requirements: a pedicle placed without kinking or twisting, good drainage, a well-defined recipient vessel, integrity of the endothelium, and duration of ischemia. The extent of skin and muscle necrosis increases significantly with increases in ischemia time. Reperfusion of ischemic tissue results in local and systemic damage associated with the release of oxygen free radicals, polymorphonuclear leucocytes, and such endothelial hormones as endothelin-1, EDRF (endothelial-derived relaxing factor), thromboxane, complement, and cytokines. Ischemia-reperfusion disrupts the delicate balance that maintains homeostasis in the microcirculation. This review discusses the clinical and therapeutic aspects of such injury, concentrating on perioperative management in free flap transfer. It points out the possible influence of endothelin-1 on vasospasm at the site of anastomosis, and emphasizes the importance of the endothelium as a highly dynamic network. Finally, future diagnostic and therapeutical aspects are discussed.
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PMID:Influence of transendothelial mechanisms on microcirculation: consequences for reperfusion injury after free flap transfer. Previous, current, and future aspects. 1704 33

Platelet hyperaggregability and associated thrombosis have been documented in a number of cardiovascular disease states. While one of the current mainstays of anti-thrombotic treatment (i.e. aspirin, clopidogrel, glycoprotein IIb/IIIa antagonists) has been directed at reducing platelet activation and aggregation, it is apparent that there are limitations to the effectiveness of these therapies. Nitric oxide (NO) plays an important role in platelet physiology. The ability of NO to regulate cyclic guanosine-3,'5'-monophosphate (cGMP), via activation of soluble guanylate cyclase, is the principal mechanism of negative control over platelet activity. NO is not only of the endothelial source, it is also released from activated platelets, providing a negative feedback. Studies in patients with symptomatic ischemia, chronic heart failure, diabetes and various risk factors for cardiovascular disease have demonstrated that platelets from these subjects exhibit reduced responsiveness to the anti-aggregating efficacy of NO: a phenomenon termed "platelet NO resistance". It constitutes an impaired physiological response to endogenous NO (endothelium-derived relaxing factor or EDRF), and as such may contribute to the increased risk of ischemic events. NO resistance also accounts for reduced pharmaco-activity of exogenous NO donors, e.g. organic nitrates. Platelet NO resistance results largely from a combination of "scavenging" of NO by superoxide anion radical and inactivation of soluble guanylate cyclase. NO resistance has both diagnostic and prognostic implications. The current review examines the association of platelet NO resistance with pathological hyperaggregability and discusses potential therapeutic strategies targeting this abnormality.
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PMID:Platelet hyperaggregability: impaired responsiveness to nitric oxide ("platelet NO resistance") as a therapeutic target. 1832 4

Taurine is found in high concentration in smooth muscle and heart muscle (approximately 10-20 mM). We found that taurine affects NE- and KCl-induced vasoconstriction. The mechanisms regulating these vasoconstrictions mostly involve Ca2+ channels and EDRF(NO). Taurine exerted either a vasodilation or vasoconstriction depending on cellular Ca2+ concentration. When vascular tone was excessively low, taurine promoted vasoconstriction allowing the maintenance of blood pressure. On the other hand, taurine dilates vessels to increase blood flow during ischemia or hypoxia. Thus, taurine modulates vascular wall tone to maintain blood flow. These results indicate that taurine plays an important homeostatic function on vascular smooth muscles as well as cardiac muscle.
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PMID:Vascular modulation of rat aorta by taurine. 1923 34

Diabetes mellitus, a chronic metabolic disorder, is recognized as a root cause of cardiovascular disorders. A long-term and uncontrolled diabetes mellitus coincides with the cardiovascular signalling alteration, resulting in inadequacy of maintaining the cardiovascular physiology. Nitric oxide (NO) is an imperative mediator of cardiovascular physiology as its signalling is known to mediate vasodilatory, anti-platelet, anti-proliferative, and anti-inflammatory actions in vessels. In 1998, Robert Furchgott, Louis Ignarro and Ferid Murad received the Nobel Prize in Medicine or Physiology for their great discoveries concerning the role of NO (originally identified as endothelium-derived relaxing factor, EDRF) as a key signalling molecule in regulating cardiovascular physiology. The activation of phosphatidylinositol 3-kinase (PI3-K) further activates protein kinase B (PKB/Akt), which subsequently enhances eNOS activation and vascular NO generation. However, in recent studies a marked impairment in PI3-K/Akt-eNOS-NO signalling has been demonstrated in the condition of diabetes mellitus. Therefore, the defective PI3-K-Akt-eNOS-NO signalling pathways could make diabetic patients more vulnerable to cardiovascular disease pathology concerning the key functions of NO. Adenosine produced by cardiac cells has abilities to attenuate the proliferation of cardiac fibroblasts, inhibit collagen synthesis, and defend the myocardium against ischemia-reperfusion injury. However, diabetes mellitus is associated with enhanced unidirectional uptake of interstitial adenosine and reduced ability to release adenosine by cardiac cells during ATP deprivation. The reduced myocardial extracellular availability and increased uptake of adenosine could make diabetic subjects more susceptible to myocardial abnormalities. This review throws lights on diabetes mellitus-associated cardiovascular signalling alterations and their possible contribution to cardiovascular disease pathology.
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PMID:Diabetes mellitus associated cardiovascular signalling alteration: a need for the revisit. 2338 86


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