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.
University of Connecticut Health Center, School of Medicine, Farmington, USA.
A
A
Tosaki
D T
DT
Engelman
R M
RM
Engelman
D K
DK
Das
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