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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In myocardial ischemia, nonexocytotic noradrenaline release has been identified as underlying mechanism of ischemia-evoked noradrenaline release. Nonexocytotic noradrenaline release can be suppressed by inhibitors of the neuronal noradrenaline carrier (uptake), such as desipramine. Utilizing this pharmacological intervention the role of local noradrenaline release in the genesis of ischemia-induced ventricular arrhythmias was studied. Regional ischemia was induced in rat isolated perfused hearts by ligature of the left anterior descending coronary artery, and the venous effluent obtained during the first 2 min of reperfusion was used to measure the release of endogenous noradrenaline by high-performance liquid chromatography methods. Coronary occlusion caused ventricular fibrillation in a well reproducible manner with an incidence of 70 to 80% during a 30 min observation period. Blockage of uptake1 by desipramine decreased the occurrence of ischemia-induced ventricular fibrillation to 60% (0.01 mumol/l) or 20% (0.1 mumol/l), and ventricular fibrillation was completely suppressed by 1 mumol/l desipramine. Likewise, desipramine (0.01-1 mumol/l) concentration-dependently reduced endogenous noradrenaline release during 30 min of regional myocardial ischemia. Nisoxetine, a structurally unrelated inhibitor of uptake1, also suppressed ischemia-evoked ventricular fibrillation. In contrast to its antifibrillatory effect during regional myocardial ischemia, desipramine precipitated arrhythmias when ventricular fibrillation was induced by perfusing normoxic hearts with exogenous noradrenaline. Combination of desipramine (0.1 mumol/l) with exogenous noradrenaline (0.01 to 1 mumol/l) increased the incidence of ventricular fibrillation compared to noradrenaline perfusion alone. Under these conditions, uptake1-blockade is known to increase the extracellular concentration of the perfused noradrenaline. Finally, in the isolated, spontaneously beating papillary muscle of the left rat heart, desipramine (0.1 and 1.0 mumol/l) had no effect on the upstroke velocity of action potentials, the action potential duration and the effective refractory period. In conclusion, the findings demonstrate that nonexocytotic noradrenaline release is an important mediator of ischemia-induced ventricular fibrillation in isolated hearts of the rat. It is also documented that uptake1 inhibitors such as desipramine reveal their effects on ventricular fibrillation secondary to their action on transmembrane noradrenaline transport.
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PMID:Nonexocytotic noradrenaline release and ventricular fibrillation in ischemic rat hearts. 875 Oct 77

The contribution of adrenergic stimulation to the proarrhythmic effects of pinacidil (30 microM), an opener of ATP-sensitive potassium channels (K+ATP), was tested in an isolated guinea-pig heart model of global ischemia (10 min) and reperfusion (10 min). None (0%) of the control hearts (n=10) elicited arrhythmias during ischemia or reperfusion. In the pinacidil-treated group, one heart (5%) experienced episodes of ventricular tachycardia (VT)/fibrillation (VF) during normoxia. During ischemia, 63% (12 out of 19) of pinacidil-treated hearts exhibited episodes of VT or VF. Hearts not in VT or VF (n=7) at the time of reperfusion, exhibited 71% VT and 43% VT/VF upon reperfusion. Proarrhythmic effects of pinacidil during ischemia or reperfusion were completely reversed by glyburide (n=9; 10 microM), a K+ATP antagonist, or nadolol (n=9; 3 microM), a beta-adrenergic antagonist. Isoproterenol (n=10; 50 nM), a beta-adrenergic agonist, induced a 20% incidence of ischemic VT and VF, and a 70% incidence of reperfusion VF, while methoxamine (n=10; 10 microM), an alpha-adrenergic agonist, demonstrated little proarrhythmia (20% VT/VF at reperfusion only). Proarrhythmic effects of isoproterenol were reversed by nadolol, but not glyburide. Pinacidil caused a slight potentiation of tachycardia induced by a bolus injection of tyramine (30 micro g), an indirectly acting sympathomimetic, but bolus injections of pinacidil (100 micro g) had no effect on heart rate. Nisoxetine, a catecholamine uptake 1 inhibitor, had no proarrhythmic effects when given alone. Catecholamine levels were reduced in pinacidil-treated hearts relative to vehicle-treated. In conclusion, it is suggested that the proarrhythmic effects of pinacidil following global ischemia and reperfusion in the isolated perfused guinea-pig heart appears to involve stimulation of beta-adrenoceptors. These proarrhythmic effects of pinacidil do not appear to be mediated solely through direct opening of K+ATP, but rather through an indirect enhancement of catecholamine release.
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PMID:Proarrhythmic effects of pinacidil are partially mediated through enhancement of catecholamine release in isolated perfused guinea-pig hearts. 951 18