A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias.
A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias.
复制标题
卤化碳引起的心脏敏化性心律失常的可能机制。
DOI：
10.1016/j.yjmcc.2006.07.003
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发表时间：
2006
影响因子：
5
通讯作者：
DudleyJr,SamuelC
中科院分区：
文献类型：
--
作者：
Jiao,Zhe;DeJesús,VíctorR;Iravanian,Shahriar;Campbell,DanielP;Xu,Jie;Vitali,JuanA;Banach,Kathrin;Fahrenbach,John;DudleyJr,SamuelC
心脏致敏是用于与在存在儿茶酚胺的情况下暴露于吸入性卤化碳相关的恶性室性心律失常的术语。我们研究了与心肌细胞暴露于肾上腺素和已知与心脏致敏相关的卤化碳（哈龙1301，CF 3Br）相关的电生理变化。心肌细胞（CMs）分离自新生大鼠和多电极阵列（MEA）上生长。肾上腺素暴露后，CM峰间期（ISI）在10 μg/L和100 μg/L时分别较基线降低14%（P<0.05）和27%（P<0.05）。单独使用哈龙（50 mg/L）可轻度延长场电位（FP）持续时间（7%）。肾上腺素（100 μg/L）和哈龙（50 mg/L）联合作用15 min，与肾上腺素单独作用相比，肌间电指数（ISI）增加（35±12%），传导速度下降（38%），差异有显著性（P<0.05）。与肾上腺素单独使用相比，场电位特性无变化，但去磷酸化连接蛋白43（Cx 43）增加60±16%（P<0.05）。用冈田酸（一种磷酸酶抑制剂）治疗，可防止暴露于哈龙和肾上腺素后Cx43去磷酸化和传导速度降低。此外，肾上腺素和哈龙诱导的电生理变化与差距连接抑制剂庚醇所见的变化无法区分。总之，卤化碳和肾上腺素的组合导致独特的电生理特征，包括缓慢的传导，这可以部分解释心脏致敏的基础。传导的减慢最有可能与Cx43磷酸化状态的变化有关。
Cardiac sensitization is the term used for malignant ventricular arrhythmias associated with exposure to inhaled halocarbons in the presence of catecholamines. We investigated the electrophysiological changes associated with cardiomyocyte exposure to epinephrine and a halocarbon known to be associated with cardiac sensitization (halon 1301, CF3Br). Cardiomyocytes (CMs) were isolated from neonatal rats and grown on multielectrode arrays (MEAs). Upon exposure to epinephrine, the CM inter-spike interval (ISI) was decreased 14% at 10 μg/L (P<0.05) and 27% at 100 μg/L (P<0.05) as compared to baseline. Halon alone (50 mg/L) mildly prolonged the field potential (FP) duration (7%). CMs exposed to combinations of epinephrine (100 μg/L) and halon (50 mg/L) for 15 min showed a blunted increase in the ISI (35±12%) and a 38% decrease in conduction velocity (P<0.05) when compared to epinephrine alone. There was no change in field potential properties, but dephosphorylated connexin 43 (Cx43) was increased 60±16% with the combination as compared to epinephrine alone (P<0.05). Treatment with okadaic acid, a phosphatase inhibitor, prevented the Cx43 dephosphorylation and the reduction in conduction velocity upon exposure to halon and epinephrine. Moreover, the electrophysiological changes induced by epinephrine and halon were indistinguishable from those seen with the gap junction inhibitor heptanol. In conclusion, the combination of a halocarbon and epinephrine results in a unique electrophysiological signature including slow conduction that may explain, in part, the basis for cardiac sensitization. The slowing of conduction is most likely related to changes in the phosphorylation state of Cx43.