Diabetes and ATP-sensitive potassium channel openers and blockers in isolated ischemic/reperfused hearts.
The incidence of reperfusion ventricular fibrillation (VF) and tachycardia (VT), heart function and the maldistribution of cardiac cations were studied in isolated ischemic/reperfused hearts obtained from streptozotocin-induced diabetic rats. Effects of an ATP-sensitive potassium (KATP) channel opener, cromakalim, and a KATP channel blocker, glibenclamide, also were studied. After 2 and 8 weeks of diabetes, hearts were isolated and subjected to 30 min of ischemia followed by reperfusion. After 2 weeks of diabetes, the incidence of VF and VT was reduced from their nondiabetic control values of 100 and 100 to 42% (P < .05) and 50% (P < .05), respectively. The reduction in VF and VT was not observed with progressive diabetes and after 8 weeks cardiac failure developed. In the 8-week diabetics, the development of cardiac failure was reflected in the aggravation of heart function (26, 16 and 17% reductions in aortic flow, left ventricular developed pressure and first derivative of developed pressure, respectively), and ion shifts (56 and 71% accumulation in cellular Na+ and Ca++, respectively, and 15% loss in cell K+) before the induction of ischemia. After ischemia/reperfusion, these changes were pronounced in diabetic groups. Cromakalim aggravated and glibenclamide attenuated the incidence of arrhythmias, contractile function and ion shifts induced by ischemia/reperfusion in diabetic hearts. The data show that the use of KATP channel openers as anti-ischemic agents may be of particular concern in the population of postinfarction diabetic patients who are known to be at high risk of sudden coronary death.
Tosaki
A
A
University of Connecticut Health Center, School of Medicine, Farmington, USA.
Engelman
D T
DT
Engelman
R M
RM
Das
D K
DK
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D019806:Cromakalim; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005905:Glyburide / Q000494:pharmacology; D006334:Heart Function Tests; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D000889:Anti-Arrhythmia Agents; D001578:Benzopyrans; D002412:Cations; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D013311:Streptozocin; D000255:Adenosine Triphosphate; D005905:Glyburide