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001-es BibID:BIBFORM041208
Első szerző:Tósaki Árpád (kísérletes farmakológus, gyógyszerész)
Cím:Extracellular Mg++ manipulation prevents the proarrhythmic activity of cromakalim in ischemic/reperfused diabetic hearts / Árpád Tósaki, Dipak K. Das
Dátum:1997
Megjegyzések:Cromakalim, an adenosine triphosphate-sensitive potassium channel opener, shows proarrhythmic activity at moderate doses (1-10 micromol/liter) in the ischemic and reperfused myocardium. We studied the effects of extracellular Mg++ (Mg++o) on the incidence of reperfusion-induced ventricular fibrillation and ventricular tachycardia in isolated working hearts (n = 12 in each group) subjected to 20 min of global ischemia followed by 30 min of reperfusion, a model eliciting a low incidence of reperfusion arrhythmias, obtained from 8-wk streptozotocin-induced diabetic rats. Cromakalim, at a concentration of 3 micromol/liter, perfused 5 min before the induction of ischemia and throughout reperfusion increased the incidence of ventricular fibrillation and ventricular tachycardia from their drug-free diabetic control values of 25 and 42% (Mg++o = 1.2 mmol/liter) to 92% (P < .05) and 100% (P < .05), respectively. Glibenclamide at a concentration of 3 micromol/liter prevented the proarrhythmiac activity of cromakalim. Increasing concentration of Mg++o to 2.4, 3.6 and 4.8 mmol/liter in the perfusion buffer, the arrhythmogenic effect of cromakalim was also abolished. Thus, with 2.4, 3.6 and 4.8 mmol/liter of Mg++o perfused before the administration of cromakalim and the onset of ischemia, the incidence of reperfusion-induced ventricular tachycardia was reduced from 92% (in cromakalim treated group) to 67%, 42% (P < .05), and 25% (P < .05), respectively. The incidence of reperfusion-induced ventricular tachycardia showed the same pattern. Elevated Mg++o prevented the cromakalim-induced cellular Na+ gain and K+ loss, measured by atomic absorption spectrophotometer. Mg++o could prevent the proarrhythmic activity of cromakalim, and the use of cromakalim as an antihypertensive or antiischemic agent may be of particular concern in the population of postischemic diabetic subjects who are known to be at high risk of sudden coronary death.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Journal of Pharmacology and Experimental Therapeutics. - 282 : 1 (1997), p. 309-317. -
További szerzők:Das, Dipak Kumar
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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