Ischemic preconditioning protection against stunning in conscious diabetic sheep: role of glucose, insulin, sarcolemmal and mitochondrial KATP channels
Ischemic preconditioning protection against stunning in conscious diabetic sheep: role of glucose, insulin, sarcolemmal and mitochondrial KATP channels
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DOI：
10.1016/s0008-6363(02)00468-6
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发表时间：
2002-08-15
影响因子：
10.8
通讯作者：
Negroni, JA
中科院分区：
文献类型：
--
作者：
del Valle, HF;Lascano, EC;Negroni, JA
肌层和线粒体atp敏感钾（KATP）通道被认为参与对梗死和昏迷的预处理保护。然而，这些结构似乎在糖尿病中发生了改变，因此，预处理可能不会在糖尿病心脏中发生。目的：本研究旨在了解清醒糖尿病(D)羊早期（EP）和晚期（I-P）抗休克缺血预处理是否发生，以及糖尿病是否影响KATP通道功能。方法：阉割的骡子羊接受四氧嘧啶一水灌胃（1 g），分为3个实验组：对照组[DC，缺血12 min (i)后再灌注2 h (r)]，早期预处理（DEP，在12 min i之前45 min进行6次5 min i-5 min r）和晚期预处理（DLP，与DEP相同，只是预处理刺激在12 min i之前24 h进行）。再灌注期间的区域力学通过壁增厚分数（%WTH）评估，并以基础值的百分比（100%）表示，通过单相动作电位持续时间（MAPD）间接评估KATP通道行为与格列本脲阻断（0.1和0.4 mg/kg）的敏感性。将结果与正常(N)羊的结果进行比较。通过给药格列本脲（0.1和0.4 mg/kg）、5-羟癸酸酯（5- hd， 5 mg/kg静脉注射）和/或二氮氧化物（10 mg/kg /min，超过90 min）来评估肌层和线粒体KATP通道阻断对昏迷恢复的影响。还评估了正常动物的急性高血糖(H)和糖尿病羊的胰岛素(I)治疗是否影响预处理保护和KATP通道行为。结果：以%WTH的平均恢复%表示的结果表明，预处理对正常绵羊的昏迷有保护作用(NC=65+/-3.5， NLP=82+/-6**， NEP=76+/-4*, *P
Sarcolemmal and mitochondrial ATP-sensitive potassium (KATP) channels have been postulated to participate in preconditioning protection against infarction and stunning. However, these structures appear to be altered in diabetes and thus, it would be possible that preconditioning does not develop in diabetic hearts. Objective: The purpose of this study was to know whether early (EP) and late (I-P) ischemic preconditioning against stunning develop in conscious diabetic (D) sheep and whether diabetes affects KATP channel function. Methods: Mule castrated sheep received alloxan monohydrate (1 g) and were ascribed to three experimental groups: control [DC, 12 min of ischemia (i) followed by 2 h of reperfusion (r)], early preconditioning (DEP six 5 min i-5 min r periods were performed 45 min before the 12 min i) and late preconditioning (DLP, same as DEP except that the preconditioning stimulus was performed 24 h before the 12 min i). Regional mechanics during reperfusion was evaluated by wall thickening fraction (%WTH) and expressed as percentage of basal values (100%), and KATP channel behavior was indirectly assessed by monophasic action potential duration (MAPD) in relation to its sensitivity to glibenclamide blockade (0.1 and 0.4 mg/kg). The results were compared to those obtained in normal (N) sheep. The effects of sarcolemmal and mitochondrial KATP channel blockade on recovery from stunning were assessed by administration glibenclamide (0.1 and 0.4 mg/kg) and 5-hydroxydecanoate (5-HD, 5 mg/kg i.v.) and/or diazoxide (10 mug/kg/min over 90 min). Whether acute hyperglycemia (H) in normal animals and insulin (I) treatment in diabetic sheep affected preconditioning protection and KATP channel behavior were also evaluated. Results: Results expressed as mean % recovery of %WTH showed that preconditioning protected against stunning in normal sheep (NC=65+/-3.5, NLP=82+/-6**, NEP=76+/-4*, *P