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)

Myocardial ischemia is associated with an intracellular acidosis recovering after reperfusion. Alpha 1-adrenergic stimulation (alpha 1) exacerbates ischemic injury and triggers ventricular arrhythmias during the reperfusion phase. We have tested the hypothesis that the arrhythmogenic effect of alpha 1 is due to a cytosolic alkalinization secondary to proteinkinase C (PKC)-dependent activation of the sarcolemmal Na+/H+ exchanger. In addition, the effect of the 2 distinct receptor subtypes, alpha 1A and alpha 1B, has also been evaluated. We used single, enzymatically dissociated, adult rat ventricular myocytes. Cells were loaded with the ester derivative of the Ca2+ probe, indo-1 or with the intracellular pH probe SNARF-1. Fluorescence was monitored simultaneously with contractility and was taken as an index of intracellular [Ca2+] or as pHi value. Cells on a stage of an inverted microscope were superfused with a bicarbonate buffer continuously gassed with 95% O2 and 5% CO2 (pH = 7.37; Ca2+ 1.5 mM) and electrically stimulated at 0.5 Hz, at 25 degrees C. Alpha 1 (phenylephrine 50 microM + nadolol 1 microM) increased twitch amplitude and pHi (delta pHi = 0.05 +/- 0.01; pHi in control = 7.24 +/- 0.06, n = 10; p < 0.05). This effect was abolished by the PKC inhibitor staurosporine (5 nM), by overnight (12-24 hours) exposure to 0.2 microM phorbol esters and by the perfusion with 10 microM ethylisopropylamiloride (EIPA), a Na+/H+ exchange inhibitor. During 15 min of hypercarbic acidosis, achieved by switching to a buffer equilibrated with 85% O2 and 15% CO2 (pH = 7.01), alpha 1 had a more pronounced effect on pHi (delta pHi = 0.11 +/- 0.02; pHi in control = 7.02 +/- 0.04, n = 10; p < 0.05). During the 10 min following the removal of acidosis, alpha 1 induced aftercontractions in 75% (n = 20) versus only 25% (n = 8) of the cells in the absence of phenylephrine (p < 0.05). Superfusion with 10 microM EIPA (n = 6) abolished the occurrence of aftercontractions. Selective alpha 1A-adrenergic receptors stimulation (alpha 1 + 2 microM CEC, which inactivates alpha 1B receptors) further increased them (92%, n = 12) whereas selective alpha 1B-adrenergic receptors stimulation (alpha 1 + 2 microM WB-4101, a alpha 1A receptors antagonist) greatly reduced the occurrence of aftercontractions (11%, n = 18). These results show that the PKC-mediated activation of the Na+/H+ exchanger is the mechanism for the arrhythmias induced by alpha 1 during simulated reperfusion after a period of acidosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Stimulation of the alpha-1 adrenergic receptors during simulated reperfusion after myocardial acidosis. The evidence for an arrhythmogenic role of the Na+/H+ exchanger]. 838 75

Although it is generally accepted that adrenergic influences contribute to arrhythmias during myocardial ischemia, it is still a matter of debate whether these arrhythmogenic effects are mediated via alpha- or beta-adrenergic receptors and which particular receptor subtype is involved. Controversial results may be due to ancillary properties of the adrenergic receptor antagonists used to resolve this question. Therefore, we compared the influence of various, structurally different alpha- and beta-adrenoceptor blocking agents on the occurrence of ventricular fibrillation in rat isolated hearts. Regional ischemia was induced by ligature of the left coronary artery and ECG was monitored over 30 min of coronary occlusion. Myocardial ischemia precipitated ventricular fibrillation in a well reproducible manner with an incidence of about 80% in control hearts. Racemic propranolol (0.1-1 micromol/l) concentration-relatedly reduced the incidence of ventricular fibrillation from 71% in controls to 10%, whereas the beta-adrenoceptor blocking agents atenolol (10 micromol/l) and timolol (1 micromol/l) did not influence the occurrence of arrhythmias. Moreover, both stereoisomers of propranolol were equipotent in suppressing ischemia-induced ventricular fibrillation, indicating an action of propranolol independent of its beta-adrenoceptor blocking properties. Unselective antagonism of alpha-adrenoceptors by phentolamine decreased the incidence of ventricular fibrillation from 90% to 58% at 0.1 micromol/l and totally suppressed ventricular fibrillation at 1 micromol/l. The alpha1-selective antagonists prazosin and HEAT concentration-dependently (0.1-10 micromol/l) reduced the incidence of ventricular fibrillation from 83% to 0%, whereas the alpha2-selective antagonist RX 821002 revealed no antiarrhythmic effect. Furthermore, subtype specific antagonism of alpha1A-adrenoceptors by WB 4101 clearly reduced the occurrence of ventricular fibrillation in a concentration-dependent manner (0.01-1 micromol/l) from 66% to 17%. Conversely, CEC, known to block the alpha1B-adrenoceptor subtype, possessed no antifibrillatory effect. In conclusion, the contribution of catecholamines to ischemia-induced arrhythmias in rat isolated heart is primarily mediated via WB 4101-sensitive alpha1-adrenergic activation. Beta- and alpha2-adrenoceptor blockade did not affect ventricular fibrillation in this model. The antifibrillatory action of propranolol was rather due to ancillary properties of this agent.
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PMID:Influence of alpha- and beta-adrenoceptor antagonists on ventricular fibrillation in ischemic rat hearts. 922 91

The purpose of this study was to assess the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after a brief incubation with cultured EECs. EECs were isolated from the right ventricles of porcine hearts and coronary artery endothelial cells (C-ECs) were also isolated from the same animals. After brief incubations (2-min) of platelet suspensions with cultured EEC and CEC monolayers, platelet aggregation in response to thrombin and 6-keto-PGF1 alpha (a stable metabolite of PGI2) content of platelet suspensions were measured. Platelet aggregation was significantly inhibited by a brief incubation of platelet suspensions with EEC and C-ECs monolayers. Pretreatment of EECs and C-ECs with indomethacin (5 x 10(-5) M) restored platelet activity, but pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME, 5 x 10(-5) M) or hemoglobin (1 x 10(-6) M) did not. Platelet/EEC interactions multiplicatively increased the 6-keto-PGF1 alpha content of platelet suspensions and the 6-keto-PGF1 alpha content of platelet suspensions after incubations with EECs correlated significantly with the inhibition of platelet aggregation. Both the anti-aggregation properties and 6-keto-PGF1 alpha production were significantly greater in EECs than in C-ECs. A brief incubation (2-min) with PDGF (10 ng/ml) or TGF-beta (1 and 10 ng/ml) stimulated 6-keto-PGF1 alpha production in EECs but not in C-ECs, although these growth factors stimulated 6-keto-PGF1 alpha production in C-ECs after a longer incubation time (30 or 60 min). In this study, after a brief incubation (2-min) with platelet suspensions, EECs inhibited platelet aggregation mainly through the release of PGI2 but not EDRF. As this anti-aggregation property was significantly greater in EECs than in C-ECs, it is suggested that endocardial endothelial PGI2 may inhibit both intracardiac and intracoronary artery thrombus formation, contributing to the prevention of myocardial ischemia.
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PMID:Antithrombotic effects of endocardial endothelial cells-comparison with coronary artery endothelial cells. 924 71