Long-term protection and mechanism of pacing-induced postconditioning in the heart.
Long-term protection and mechanism of pacing-induced postconditioning in the heart.
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DOI：
10.1007/s00395-010-0095-2
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发表时间：
2010-07
影响因子：
9.5
通讯作者：
Prinzen FW
中科院分区：
文献类型：
--
作者：
Babiker FA;Lorenzen-Schmidt I;Mokelke E;Vanagt WY;Delhaas T;Waltenberger J;Cleutjens JP;Prinzen FW
再灌注早期阶段的短暂心室起搏（起搏诱导后处理，PPC）已被证明可以减少再灌注 2 小时后测量的梗塞面积。在本研究中，我们研究了（1）PPC 是否导致梗塞面积持续减少，（2）异步激活引起的异常机械负荷是否是 PPC 的触发因素，以及（3）参与 PPC 的信号通路。兔心脏在体内进行 30 分钟的冠状动脉闭塞，然后进行 6 周的再灌注。 PPC 包括 10 个间隔 30 秒的左心室 (LV) 起搏，从再灌注开始。 PPC 减少了标准化至危险区域的梗塞面积（TTC 染色），从对照组的 49.0 ± 3.3% 减少到 PPC 兔子的 22.9 ± 5.7%。在离体射血兔心脏中，用双心室起搏代替左心室起搏消除了 PPC 的保护作用，而 10 个 30 秒的高预负荷周期提供了与 PPC 类似的保护作用。 PPC 的保护作用既不受腺苷受体阻断剂 8-SPT 的影响，也不受血管紧张素 II 受体阻断剂坎地沙坦的影响，但被细胞骨架微管破坏剂秋水仙碱消除。线粒体 KATP 通道 (5HD)、PKC（白屈菜红碱）和 PI3 激酶（渥曼青霉素）的阻断剂均会消除 PPC 提供的保护。在原位猪心脏中，PPC 将梗塞面积从 35% ± 4% 减少到 16% ± 12%，这种保护作用被拉伸激活的通道阻滞剂钆所消除。如果 PPC 应用延迟 5 分钟或仅使用 5 个起搏周期，则不会减少梗塞面积。本研究表明（1）PPC 永久减少心肌损伤，（2）异常机械负荷比电刺激或 G 偶联受体刺激更可能触发 PPC，（3）PPC 可能与其他心脏保护模式共享下游通路。
Brief periods of ventricular pacing during the early reperfusion phase (pacing-induced postconditioning, PPC) have been shown to reduce infarct size as measured after 2 h of reperfusion. In this study, we investigated (1) whether PPC leads to maintained reduction in infarct size, (2) whether abnormal mechanical load due to asynchronous activation is the trigger for PPC and (3) the signaling pathways that are involved in PPC. Rabbit hearts were subjected to 30 min of coronary occlusion in vivo, followed by 6 weeks of reperfusion. PPC consisted of ten 30-s intervals of left ventricular (LV) pacing, starting at reperfusion. PPC reduced infarct size (TTC staining) normalized to area at risk, from 49.0 ± 3.3% in control to 22.9 ± 5.7% in PPC rabbits. In isolated ejecting rabbit hearts, replacing LV pacing by biventricular pacing abolished the protective effect of PPC, whereas ten 30-s periods of high preload provided a protective effect similar to PPC. The protective effect of PPC was neither affected by the adenosine receptor blocker 8-SPT nor by the angiotensin II receptor blocker candesartan, but was abrogated by the cytoskeletal microtubule-disrupting agent colchicine. Blockers of the mitochondrial KATP channel (5HD), PKC (chelerythrine) and PI3-kinase (wortmannin) all abrogated the protection provided by PPC. In the in situ pig heart, PPC reduced infarct size from 35 ± 4 to 16 ± 12%, a protection which was abolished by the stretch-activated channel blocker gadolinium. No infarct size reduction was achieved if PPC application was delayed by 5 min or if only five pacing cycles were used. The present study indicates that (1) PPC permanently reduces myocardial injury, (2) abnormal mechanical loading is a more likely trigger for PPC than electrical stimulation or G-coupled receptor stimulation and (3) PPC may share downstream pathways with other modes of cardioprotection.
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影响因子：
20.1
作者：
BANERJEE, A;LOCKEWINTER, C;HARKEN, AH
通讯作者：
HARKEN, AH
影响因子：
20.1
作者：
HANSEN, DE;BORGANELLI, M;TAYLOR, LK
通讯作者：
TAYLOR, LK
DOI：
10.1152/ajpheart.00379.2008
发表时间：
2008-10-01
影响因子：
4.8
作者：
Bouhidel, Omar;Pons, Sandrine;Ghaleh, Bijan
通讯作者：
Ghaleh, Bijan
影响因子：
--
作者：
OVIZE, M;KLONER, RA;PRZYKLENK, K
通讯作者：
PRZYKLENK, K
影响因子：
--
作者：
PRINZEN, FW;AUGUSTIJN, CH;RENEMAN, RS
通讯作者：
RENEMAN, RS