Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.
Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.
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远程缺血预处理对链脲佐菌素诱导的糖尿病大鼠与非糖尿病大鼠的缺血后心律失常有不同的减轻作用。
DOI：
10.1186/s12933-017-0537-3
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发表时间：
2017-04-26
影响因子：
9.3
通讯作者：
Abbott GW
中科院分区：
文献类型：
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作者：
Hu Z;Chen M;Zhang P;Liu J;Abbott GW
心源性猝死（SCD）是全球死亡率的主要原因，最常见的原因是心肌缺血，但需要额外的触发因素。糖尿病（DM）易患SCD，即使在调整了其他DM相关的心血管病变（如冠状动脉疾病）后。我们先前发现，远程肝脏缺血预处理（RLIPC）通过诱导心脏保护性RISK通路，特别是抑制GSK-3β（Ser 9）的磷酸化，对心脏缺血再灌注损伤（IRI）相关的室性心律失常和心肌梗死具有高度保护作用。我们评估了急性链脲佐菌素诱导的DM对大鼠冠状动脉结扎、IRI相关的心室重构和RLIPC治疗的影响。IRI后心律失常诱导在非糖尿病大鼠和DM大鼠中相似，但出乎意料的是，DM大鼠在再灌注期间显示出较低的SCD发生率（41 vs. 100%），表明不受控制的高血糖不会急性诱发SCD。RLIPC在非糖尿病和糖尿病大鼠中均高度有效，可降低所有类型室性快速性心律失常的发生率和持续时间，并增加潜伏期。相反，房室传导阻滞（AVB）在非糖尿病大鼠中对RLIPC高度反应（发生率从72%降至18%），但在糖尿病大鼠中无反应。RISK通路诱导在非糖尿病和糖尿病大鼠中相似，因此不能解释AVB对治疗的DM特异性抵抗。我们的研究结果揭示了糖尿病患者对室性快速性心律失常与房室传导阻滞的远程预处理反应性的重要急性特异性差异，这可能具有临床意义，因为房室传导阻滞是一种恶性心律失常，在糖尿病患者中比非糖尿病患者常见两倍，并且与血糖水平>10 mmol/L相关。
Sudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9). We evaluated the impact of acute streptozotocin-induced DM on coronary artery ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats. Post-IRI arrhythmia induction was similar in nondiabetic and DM rats, but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing incidence and duration of, and increasing latency to, all classes of ventricular tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus not explaining the DM-specific resistance of AVB to therapy. Our findings uncover important acute DM-specific differences in responsiveness to remote preconditioning for ventricular tachyarrhythmias versus AVB, which may have clinical significance given that AVB is a malignant arrhythmia twofold more common in human diabetics than nondiabetics, and correlated to plasma glucose levels >10 mmol/L.