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)

Intracoronary infusions of activated complement C5a result in myocardial ischemia, contractile dysfunction, and leukocyte accumulation. The hypothesis was tested that the generation of the coronary vasoconstrictors, thromboxane A2 and the 5-lipoxygenase leukotrienes (LTC4 and LTD4), contributes to the C5a-induced decrease in coronary blood flow and contractile function. The left anterior descending coronary artery in anesthetized swine was cannulated and servo pump-perfused with arterial blood at constant pressure and measured flow. Regional subendocardial contractile function was assessed with sonomicrometry. The interventricular vein was cannulated for sampling of coronary venous blood for leukocyte count. The responses in left anterior descending coronary artery blood flow and percent segment shortening to intracoronary infusions of LTC4 (1 microgram), LTD4 (1 microgram), thromboxane agonist U46619 (7.5 micrograms), and C5a (500 ng) were assessed before and after 1) LTD4/LTE4 receptor blockade with leukotriene receptor blocker LY171883 (10 mg/kg i.v.) (n = 5), 2) thromboxane A2/prostaglandin H2 receptor blockade with thromboxane receptor blocker BM13505 (2 mg/kg i.v.) (n = 5), and 3) combined thromboxane and leukotriene receptor blockade (n = 5). In the absence of receptor blockade, intracoronary C5a decreased coronary flow (50-60%) and regional segment function (60-70%) compared with the preinfusion levels. This was accompanied by a fall in coronary venous blood leukocyte levels by 5-6 x 10(6) cells/ml in the absence of alterations in arterial blood leukocyte count. Intracoronary injections of LTD4, LTC4, or U46619 also resulted in prompt decreases in coronary blood flow (50-60%) and segment function (70-80%) from preinfusion levels. Leukotriene receptor blockade with LY171883 abolished these responses to LTD4 and LTC4. Administration of LY171883 also attenuated (p less than 0.05) the myocardial response to C5a; coronary flow and segment function decreased by approximately 28% from preinfusion levels. Thromboxane receptor blockade with BM13505 eliminated the response in coronary flow and segment function to intracoronary U46619. Similar to LY171883, administration of BM13505 blunted (p less than 0.05) the C5a-induced decreases in coronary flow and contractile function, which fell by approximately 20-25% from the preinfusion level. After the combined LTD4/LTE4 receptor and thromboxane A2/prostaglandin H2 receptor blockade, intracoronary C5a resulted in little change in both coronary blood flow and segment shortening. In contrast to the flow and function effects, the C5a-induced myocardial leukocyte extraction was not decreased by leukotriene and/or thromboxane receptor blockade.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thromboxane A2 and peptidoleukotrienes contribute to the myocardial ischemia and contractile dysfunction in response to intracoronary infusion of complement C5a in pigs. 213 27

In this study, we have investigated the biological activities of LxA5 and LxB5 in isolated smooth muscle preparations of the guinea pig. LxA5 slowly contracted pulmonary parenchymal strips isolated from guinea pigs in a concentration-dependent manner over the range of 0.1-2.2 microM. This bronchoconstrictor effect was not associated with release of peptide leukotrienes (i.e. LTC4, LTD4 and LTE4) and only a slight increase in thromboxane B2. Furthermore, the bronchoconstrictor effect was not blocked by lipoxygenase inhibitors, suggesting the pulmonary effect is not mediated by lipoxygenase products. However, a peptide leukotriene receptor antagonist (e.g. SK&F-104353) inhibited or reversed the LxA5 response indicating that LxA5 and the peptide leukotrienes may share the same receptor. In contrast to LxA5, LxB5 displayed no significant bronchoconstrictor effect at concentrations up to 2.2 microM. Moreover, LxA5 and LxB5 did not exert a significant endothelium-dependent vasorelaxation in aortic vascular smooth muscle as do LxA4 and LxB4. Thus, LxA5 and LxB5 display a unique biological profile which differs from LxA4 and LxB4. LxA4 may be a mediator in circulatory disease states (e.g. myocardial ischemia, circulatory shock), but LxA5 and LxB5 are not as likely candidates as mediators of disease.
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PMID:Pharmacologic profile of lipoxins A5 and B5: new biologically active eicosanoids. 254 63

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