Long-term treatment with glibenclamide increases susceptibility of streptozotocin-induced diabetic rat heart to reperfusion-induced ventricular tachycardia.
Long-term treatment with glibenclamide increases susceptibility of streptozotocin-induced diabetic rat heart to reperfusion-induced ventricular tachycardia.
复制标题
长期使用格列本脲治疗会增加链脲佐菌素诱导的糖尿病大鼠心脏对再灌注诱导的室性心动过速的易感性。
DOI：
10.1142/9789812702234_0033
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发表时间：
2005
影响因子：
3.2
通讯作者：
T. Sakata
中科院分区：
文献类型：
--
作者：
N. Takahashi;T. Ooie;T. Saikawa;T. Iwao;H. Yoshimatsu;T. Sakata
本研究调查了格列本脲（GLIB）长期治疗对链脲佐菌素（STZ）诱导的糖尿病心脏缺血/再灌注损伤敏感性的影响。注射 STZ 后 4 周开始，用 GLIB（0.1 mg/kg，腹腔注射，每周 3 次，STZ-GLIB 组）或载体（STZ-VEH 组）治疗大鼠 8 周。在再灌注期间，研究了 STZ-GLIB 组（n = 14）和 STZ-VEH 组（n = 13）大鼠以及年龄匹配的对照大鼠（CNT 组，n = 14）的离体心脏的心脏功能恢复、释放的肌酸激酶（CK）和室性心律失常的发生率。每颗心脏均经历 5 分钟的整体低流量缺血，然后是 25 分钟的无流量缺血，随后进行 30 分钟的再灌注。 STZ-GLIB 组和 STZ-VEH 组之间的血浆葡萄糖水平没有显着差异。 STZ-VEH组和STZ-GLIB组再灌注期间心脏功能恢复和CK释放均显着低于CNT组（分别P < 0.01和P < 0.05）。再灌注导致 STZ-VEH 组和 STZ-GLIB 组心室颤动的发生率分别为 23% 和 21% (P = ns)。这些值显着低于 CNT 组（100%，P < 0.001）。更重要的是，STZ-GLIB组室性心动过速发生率显着高于STZ-VEH组（93% vs 54%，P < 0.05），与CNT组无显着性差异（93% vs 100%，P = ns）。结果表明，长期使用 GLIB 治疗可能会部分消除 STZ 对糖尿病心脏再灌注引起的室性心律失常的保护作用。
This study investigated the effects of long-term treatment with glibenclamide (GLIB) on the susceptibility of streptozotocin (STZ)-induced diabetic heart to ischemia/reperfusion insults. Starting 4 weeks after the injection of STZ, rats were treated with GLIB (0.1 mg/kg, ip, three times a week, STZ-GLIB group) or vehicle (STZ-VEH group) for 8 weeks. The recovery of cardiac performance, released creatine kinase (CK), and incidence of ventricular arrhythmias were studied during the reperfusion period in isolated hearts from rats in STZ-GLIB (n = 14) and in STZ-VEH groups (n = 13) and from age-matched control rats (CNT group, n = 14). Each heart was subjected to 5 min of global low-flow ischemia followed by 25 min of no-flow ischemia, with a subsequent 30 min of reperfusion. Plasma glucose level was not significantly different between the STZ-GLIB and STZ-VEH groups. The recovery of cardiac performance and the released CK during reperfusion period were significantly lower in both STZ-VEH and STZ-GLIB groups than in the CNT group (P < 0.01 and P < 0.05, respectively). Reperfusion resulted in an incidence of ventricular fibrillation in 23% and 21% in STZ-VEH and STZ-GLIB groups, respectively (P = ns). These values were significantly lower than that of the CNT group (100%, P < 0.001 for both). More importantly, the incidence of ventricular tachycardia in the STZ-GLIB group was significantly higher than that in the STZ-VEH group (93% vs 54%, P < 0.05) and was not significantly different from that in the CNT group (93% vs 100%, P = ns). The results suggest that STZ-induced protection against reperfusion-induced ventricular arrhythmias in diabetic heart may be partially abrogated by long-term treatment with GLIB.