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Altered ATP-Dependent K+ Channel
Function Makes Diabetic Heart More
Sensitive to Ischemia/Reperfusion-Induced
Arrhythmias and Myocardial Stunning
del Valle, Héctor F.; Lascano, Elena C.;
Negroni, Jorge A.
Department of Physiology, Pharmacology
Favaloro University, Buenos Aires, Argentina
Introduction: There are controversial findings regarding the sensitivity of diabetic (D) myocardium to ischemic injury. Most works have shown that D heart is more sensitive to ischemia-reperfusion injury. However the probable mechanism involved is unknown. Recently, it has been demonstrated that ATP-dependent K+ channel (KATPch), which are cardioprotectors in normal hearts, were altered in D myocytes inducing arrhythmia appearance.
Objective: The purpose was to assess whether KATPchs have a different behavior in D heart affecting the recovery from stunning and arrhythmia appearance in a conscious alloxan-induced (1gr total dose) diabetic sheep model.
Methods: 6 groups of sheep were studied (3 normal [N] and 3 D): 1) control N, (n=9) and control D (n=9): 12 min I followed by 2 hs reperfusion (R); 2) GN1 (n=9) and GD1 (n=8): the same as 1) with glibenclamide 0.1 mg/Kg ; 3) GN4 (n=6) and GD4 (n=7): the same as 2) but with glibenclamide 0.4 mg/Kg infused 30 min before I to block KATPch. Each group contained conscious and open chest experiments. Recovery of myocardial function during R was studied in conscious sheep by measurement of % wall thickening fraction (%WTH). The KATPch sensitivity to G blockade was assessed measuring action potential duration (APD) in msc during ischemia (at 6 and 12 min) in open chest animals. All values were expressed as Mean±SE.
Results: Diabetes made KATPch more sensitive to a low G dose (APD: Preischemia; D (n=6)= 320±5 vs. N (n=6)= 330±6 (NS); Ischemia: D = 310±5 vs. N = 260±7, p<0.001. The altered KATP channel sensitivity to G might explain the worsening in myocardial recovery from stunning (%WTH: D 52±3 vs. N 63±5; D 67±4 vs. N 77±3 and D 75±6 vs. N 86±4, at 60, 90 and 120 min of R, p<0.01) and the increase in arrhythmias appearance in G-treated diabetic sheep (p<0.001 vs. control diabetic and non-diabetic sheep).
Conclusion: At a low dose G blocked action potential shortening during ischemia in D but not in N sheep, indicating that D heart is more sensitive to drug effects on KATPch. This result might explain the lower recovery of function and a pronounced increase in fatal arrhythmias appearance during reperfusion in diabetic sheep.
2nd Virtual Congress of Cardiology
Dr. Florencio Garófalo
Dr. Raúl Bretal
Dr. Armando Pacher
Technical Committee - CETIFAC
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