Implantation of sinoatrial node cells into canine right ventricle: biological pacing appears limited by the substrate.

Implantation of sinoatrial node cells into canine right ventricle: biological pacing appears limited by the substrate.
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DOI:
10.3727/096368911x565038
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发表时间:
2011
影响因子:
3.3
通讯作者:
Rosen MR
Rosen MR
中科院分区:
医学4区
文献类型:
--
作者:
Zhang H;Lau DH;Shlapakova IN;Zhao X;Danilo P;Robinson RB;Cohen IS;Qu D;Xu Z;Rosen MR

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生物起搏已被提议作为电子起搏的生理对应物,并且窦房结(SAN)是生物起搏器的通用标准。我们测试了自体植入右心室(RV)时SAN起搏细胞活性的表达。我们在成年杂种犬的右心室中诱导完全性心脏传导阻滞并植入电子起搏器。通过膜片钳研究酶促分离的自体SAN细胞以确认SAN身份。将SAN细胞(400,000)注射到RV心外膜下游离壁中,并监测犬2周。起搏器功能通过双腔起搏和IV肾上腺素激发进行评估。SAN细胞表达时间依赖性内向电流(If),在超极化时激活:在−105 mV时密度= 4.3 ± 0.6 pA/pF。在24 h时,6只犬中有4只表现出>50%的搏动源自植入部位。第7-14天的生物起搏器频率= 45-55 bpm,起搏后逸搏时间= 1.5-2.5 s。出现快速的儿茶酚胺反应。植入自体SAN细胞的狗表现出与解剖SAN不同的生物起搏特性。这突出了细胞和底物相互作用在产生生物起搏器功能中的重要性。
Biological pacing has been proposed as a physiologic counterpart to electronic pacing, and the sinoatrial node (SAN) is the general standard for biological pacemakers. We tested the expression of SAN pacemaker cell activity when implanted autologously in the right ventricle (RV). We induced complete heart block and implanted electronic pacemakers in the RV of adult mongrel dogs. Autologous SAN cells isolated enzymatically were studied by patch clamp to confirm SAN identity. SAN cells (400,000) were injected into the RV subepicardial free wall and dogs were monitored for 2 weeks. Pacemaker function was assessed by overdrive pacing and IV epinephrine challenge. SAN cells expressed a time-dependent inward current (If) activating on hyperpolarization: density = 4.3 ± 0.6 pA/pF at −105 mV. Four of the six dogs demonstrated >50% of beats originating from the implant site at 24 h. Biological pacemaker rates on days 7–14 = 45–55 bpm and post-overdrive escape times = 1.5–2.5 s. Brisk catecholamine responsiveness occurred. Dogs implanted with autologous SAN cells manifest biological pacing properties dissimilar from those of the anatomic SAN. This highlights the importance of cell and substrate interaction in generating biological pacemaker function.