Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate whether PAF is related to the precipitation of pulmonary edema after myocardial ischemia, we studied the effect of a specific PAF antagonist, CV-6209, on the extravascular lung water level measured by the thermal-dye double indicator dilution method, ETV, after coronary ligation in dogs. Eight dogs served as sham control animals (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in eight dogs (group 2), and the coronary artery was ligated after pretreatment with CV-6209 (1 mg/kg) in eight dogs (group 3). The ETV increased significantly after coronary ligation in groups 2 and 3. The amount of increase in ETV in group 2 was significantly larger than in group 3. Thus, CV-6209 can prevent the accumulation of extravascular lung water after coronary ligation without producing changes in pulmonary vascular dynamics, indicating that PAF may play an important role in pulmonary edema after myocardial ischemia.
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PMID:Role of platelet-activating factor in pulmonary edema after coronary ligation in dogs. 139 76

The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A2 and leukotrienes are responsible for anaphylactic coronary constriction and negative inotropic effects. The cardiac effects of anaphylactic histamine release are related to the stimulation of two antagonistic receptor types. Histamine induces atrioventricular conduction delay and constriction of the epicardial coronary vessels via H1-receptor stimulation. H2-receptors, however, mediate coronary vasodilation and an increase in heart rate and myocardial contractility. It may therefore be concluded that administration of histamine H2-receptor antagonists is disadvantageous. During anaphylactic states, the cardiodepressive effects of the other mediators of anaphylaxis are unmasked, resulting in a sustained coronary constriction and impairment of myocardial contractility. To verify this speculation, we investigated the effects of H1- and H2-receptor antagonists on cardiovascular function of guinea pigs during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed administration of the antigen induced severe cardiac dysfunction. Within a few minutes, cardiac output markedly decreased and left ventricular end-diastolic pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of an atrioventricular block.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of histamine H1- and H2-receptor antagonists on cardiovascular function during systemic anaphylaxis in guinea pigs. 167 95

Myocardial ischemia is associated with endothelial injury and an apparently insufficient generation of endothelium-derived vasodilating and platelet and white cell inhibitory mediators, such as prostacyclin (PGI2) and EDRF. This paper reviews some recent findings of our laboratory on cardioprotective effects of defibrotide, a PGI2 stimulating agent, in experimental myocardial ischemia and its possible sites of action in several in vitro assay systems. Defibrotide (32 mg/kg x h) reduced the infarct size by 50% in pigs, subjected to 1 h of coronary artery ligation followed by 3 h of reperfusion. This was associated with significant inhibition of neutrophil activation during the reperfusion period and a two-to threefold increase in cardiocoronary PGI2 generation. In vitro studies on PAF- and calcium ionophore-stimulated human granulocytes confirmed a dose-dependent (10-1000 micrograms/ml) antineutrophil effect of defibrotide (inhibition of lysosomal enzyme release) which was independent of the type of stimulus. Defibrotide (0.1 mg/ml) also inhibited superoxide anion generation from PAF stimulated neutrophils in Langendorff-perfused guinea pig hearts and was equipotent to a specific PAF antagonist (BN 52021). Defibrotide (0.1 mg/ml) did not stimulate PGI2 release from cultured porcine aortic endothelial cells but enhanced PGI2 release four- to fivefold above control if endothelial cells were coincubated with platelets. These data demonstrate a considerable cardioprotective potential of defibrotide which appears to involve endothelial protection from granulocyte-derived noxious compounds and a long-lasting stimulation of PGI2 production.
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PMID:Endothelial protection by defibrotide--a new strategy for treatment of myocardial infarction? 255 54

PAF is a phospholipid formed from the action of phospholipase A2 upon cellular membranes in response to immunologic or hypoxic stimuli. PAF does not exist in its active form as a storage product within cells, but is synthesized rapidly after phospholipase A2 activation. A potent lipid released by multiple cell types in mammalian systems, the emerging perspective is that PAF is a major endogenous mediator influencing the pathogenesis and outcome of ischemia and conditions of circulatory shock. These effects appear to be especially relevant to the syndrome of MSOF during critical illness. All of the major criteria for validation of a shock factor have been fulfilled for PAF. First, PAF has been measured in biological fluid of animals during shock states, although this is not an easy task since PAF is formed in minute amounts and is rapidly metabolized. Nevertheless, combinations of high pressure liquid chromatography (HPLC) and bioassay methods employing washed rabbit platelets have been successfully utilized in this regard. Second, synthetic PAF has been injected into cell suspensions, isolated tissues, and live animals, where it produces most of the effects attributed to endogenous PAF released by immunologic or hypoxic stimuli. These studies have shown that PAF exerts a variety of pathophysiologic actions, including (1) cardiodepression (that is, a negative inotropic effect), (2) reductions in systemic blood pressure, (3) leakage of fluid from the microvasculature, (4) bronchoconstriction, and (5) platelet aggregation. All of these actions of PAF can initiate or exacerbate shock and ischemic injury in multiple organ systems. Third, specific PAF receptor antagonists have been found to markedly attenuate the severity of endotoxic, anaphylactic, hemorrhagic, and traumatic shock, as well as acute myocardial ischemia. In all these conditions, a variety of PAF receptor antagonists (including PAF analogues and structurally dissimilar substances) have improved survival and have retarded pathophysiologic processes believed to be important in causing tissue injury. These processes include lysosomal membrane damage and proteolysis. Moreover PAF receptor antagonists attenuate the release of secondary toxic factors in shock, such as myocardial depressant factor. Thus, administration of specific PAF receptor antagonists early in the course of circulatory shock and organ ischemia may prove to be useful therapeutic agents in a variety of life-threatening disorders. In addition to having direct actions, PAF appears to function as a pivotal agent in a chain of mediators producing tissue injury. Recent evidence suggests that tumor necrosis factors (i.e., cachectin) stim
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PMID:Induction of tissue injury and altered cardiovascular performance by platelet-activating factor: relevance to multiple systems organ failure. 265 Aug 21

PAF is a phospholipid formed from the action of phospholipase A2 triggered by immunologic or hypoxic stimuli. PAF does not exist in its active form but rather is present as a storage product within cells, and is synthesized rapidly upon appropriate activation. PAF is a potent lipid mediator which is released by a variety of cell types in mammalian systems. PAF appears to be a particularly important mediator of myocardial ischemia and circulatory shock states in mammalian species. Moreover, since PAF releases other lipid mediators, it may have an "amplifier" role in the propagation of circulatory disease states.
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PMID:Platelet activating factor (PAF) and its role in cardiac injury. 267 33

A potent phospholipid (platelet-activating factor, PAF) has been implicated in a variety of inflammatory and ischemic responses (eg, myocardial ischemia and anaphylactic shock). In isolated rat hearts perfused at constant flow, PAF produced a dose-dependent increase in coronary perfusion pressure (CPP) and a decrease in contractile force (CF). At 20 nM, PAF increased CCP by 21 +/- 1 mm Hg and decreased CF by 31 +/- 3% in nine hearts. At the peak of the PAF response, coronary effluent contained LTC4, LTD4, and LTE4 (0.22 +/- 0.05 pmol/ml) and TxB2 (0.97 +/- 0.16 pmol/ml). Addition of specific PAF receptor antagonists (eg, BN-52021 and CV-3988) inhibited peptide leukotriene and TxB2 production and blocked the coronary vasoconstriction and decrease in contractile force. Cyclooxygenase inhibitors (eg, naproxen) or specific TxA2 receptor antagonists (eg, BM-13,505) failed to prevent the increase in CPP or the decrease in CF. Furthermore, a lipoxygenase inhibitor (ie, propyl gallate) or a specific LTD4 receptor antagonist (ie, LY-171,883) prevented the increase in CPP but did not antagonize the negative inotropic response. These data indicate that the coronary constriction in the isolated perfused rat heart is a result of the PAF-induced release of endogenous peptide leukotrienes but not TxA2 production. However, the negative inotropic response appears to be partly due to a direct negative inotropic action of PAF on cardiac muscle. Thus, PAF produces a variety of direct actions and indirect effects via release of eicosanoid mediators contributing to cardiac impairment in the rat heart.
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PMID:Mechanisms of platelet-activating factor-induced cardiac depression in the isolated perfused rat heart. 282 6

Changes in Ca++ concentration were studied in platelets of patients with acute myocardial infarction, unstable or stable angina pectoris and those of healthy donors by means of fluorescent probe Quin-2 AM. Influence of aggregation inductors on the process of Ca++ level increase in these cells was also investigated. Intracellular Ca++ concentration increased in patients with acute myocardial infarction in the presence of PAF 2.10(-7) M (1337 +/- 255 nM) and in the presence of ADP 10(-5) M (1767 +/- 296 nM). A certain increase in calcium responses to stimulators was observed also in patients with unstable or stable angina pectoris. Dynamic follow up of patients with acute myocardial infarction starting from the 14th day demonstrated significant fall in intracellular Ca++ concentration (from 1767 +/- 296 nM to 834 +/- 186 nM, p less than 0.01). Platelet sensitivity to inductors during the course of therapy did not change significantly in patients with stable angina pectoris and tended to decrease in those with unstable angina pectoris (from 707 +/- 274 nM to 410 +/- 95 nM, p greater than 0.05). Increase in platelet aggregability and in calcium responses to stimulators in patients with IHD is an evidence of calcium metabolism disturbances which play an important role in the pathogenesis of the disease.
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PMID:[Calcium metabolism of the thrombocytes in ischemic heart disease]. 323 56

These studies were performed to investigate a role of PAF in the genesis of life-threatening arrhythmias and platelet aggregation accompanying myocardial ischaemia and reperfusion. Pretreatment with the PAF antagonists SRI 63-441 (10 mgkg-1 iv) and BN 52021 (5 mgkg-1 iv) significantly reduced the number of arrhythmias during a thirty minute coronary artery occlusion period in open-chest anaesthetised greyhounds, particularly ventricular tachycardia. Both drugs also reduce the incidence of ventricular fibrillation resulting from reperfusion of the myocardium. Myocardial ischaemia in control animals resulted in a marked fall in platelet count in blood draining the ischaemic area, which was abolished by both SRI 63-441 and BN 52021. These results suggest a role for PAF in the genesis of ischaemia and reperfusion-induced arrhythmias, possibly by inducing platelet aggregation.
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PMID:The effects of PAF antagonists on ischaemia and reperfusion arrhythmias and ischaemia-induced platelet aggregation. 324 8

PAF-acether (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) has been implicated in a variety of inflammatory and ischaemic disorders (e.g., myocardial ischemia, anaphylactic shock). Recently, the peptide leukotrienes (i.e., LTC4, LTD4) have been shown to mediate the increase in coronary vascular resistance induced by PAF-acether in the isolated perfused rat heart. In isolated perfused guinea pig hearts, PAF-acether produced a dose-dependent increase in coronary perfusion pressure (CPP) and a decrease in contractile force (CF). At 50 pmol/l, PAF increased CPP by 13 +/- 3 mm Hg and decreased CF by 47 +/- 12% in 8 hearts. Radioimmunoassay of the coronary effluent did not detect peptide leukotrienes or thromboxane B2 (TxB2) in response to PAF. Addition of a specific PAF-acether receptor antagonist, CV-6209 (25 nmol/l), blocked the increase in coronary perfusion pressure and decrease in contractile force. OKY-1581 (400 nmol/l), a thromboxane synthetase inhibitor or LY-171,883 (7.3 mumol/l) a leukotriene D4 receptor antagonist, failed to prevent the increase in CPP or the decrease in CF. These data indicate that the PAF-acether induced increase in CPP is not mediated by the peptide leukotrienes or thromboxane A2 (TxA2). Possible mechanisms for the increase in CPP induced by PAF-acether in the isolated perfused guinea pig heart include a direct receptor mediated constriction of coronary resistance vessels, release of a non-eicosanoid coronary constrictor as a mediator of the response, or via enhancement of coronary microvascular permeability.
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PMID:PAF-acether induced cardiac dysfunction in the isolated perfused guinea pig heart. 343 98

Thirty-seven men with angiography or ultrasound confirmed peripheral arterial occlusive disease were divided into two groups. Group 1 included 24 patients treated with one daily infusion of 10 g of phosphocreatine in 200 ml of solvent for 10 days. Group 2 included 13 patients who were given 0.9% NaCl in the same scheme. Groups were comparable in: duration of intermittent claudication, maximal walking distance, Ketle index, cholesterol, triglycerides, frequency of ischemic heart disease, hypertension, diabetes, smoking. Patients were examined 4 times: before starting, on second day, after treatment period, and 1 month after. Treadmill-test; ADP-, PAF-, 5-HT-induced platelet aggregation; D-dimer; PAI-1 activity; blood viscosity at high and low shear rate; hematocrit were performed. After treatment maximal walking distance significantly increased in patients of Group 1. Mechanisms of this effects include positive influence of phosphocreatine on platelet aggregation, blood rheology, coagulation and fibrinolytic systems.
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PMID:The effect of exogenous phosphocreatine on maximal walking distance, blood rheology, platelet aggregation, and fibrinolysis in patients with intermittent claudication. 807


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