On the mechanisms of arrhythmias in the myocardium of mXinalpha-deficient murine left atrial-pulmonary veins.

On the mechanisms of arrhythmias in the myocardium of mXinalpha-deficient murine left atrial-pulmonary veins.
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DOI:
10.1016/j.lfs.2008.06.020
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发表时间:
2008-08-15
期刊:
影响因子:
6.1
通讯作者:
Lin, Cheng-I
Lin, Cheng-I
中科院分区:
医学2区
文献类型:
--
作者:
Lai, Yu-Jun;Huang, Eagle Yi-Kung;Yeh, Hung-I;Chen, Yen-Lin;Lin, Jim Jung-Ching;Lin, Cheng-I

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我们之前已经证明,左房-肺静脉组织(LA-PV)可以在野生型(mXinα+/+)小鼠中产生折返性心律失常(房颤,AF),但在mXinα-空(mXinα-/-)小鼠中不会。通过本实验,我们研究了mXinα+/+与mXinα-/-LA-PV的致心律失常活性及其可能的机制。用MED64系统记录LA-PV的电活动和传导速度(CV)。MXinα+/+组的CV明显快于mXinα-/-LA-PV组,1μ异丙肾上腺素可使其增加。快速起搏可在mXinα+/+诱发房颤,但在可出现自动节律的mXinα-/-LA-PV不能诱发房颤。异丙肾上腺素增加Xinα+/+的房颤发生率,增加mXinα-/-LA-PV的自动节律发生率。在附着性右心房的LA-PV(RA-LA-PV)中,所有准备均出现自动节律。在mXinα+/+RA-LV-PV中,异丙肾上腺素、毒毛旋花苷和阿托品同时治疗后,自动节律的发生率基本相同,但房颤显著增加。而在相同条件下,mXinα-/-RA-LA-PV的自动节律明显增强,但仍未出现房颤。常规微电极技术显示mXinα-/-较mXinα+/+LA-PV的APD90值更长,最大舒张期电位负值更小。全细胞电流钳实验也显示,mXinα-/-与mXinα+/+LA-PV相比,mXin DNA-/-的mDP值较低。MXinα+/+可在多种情况下通过快速起搏诱发房颤,而MXinα-/-LA-PV不能诱发房颤,这可能是由于MXinα-/-心肌细胞CV减慢、APD90延长、Mdp负性减轻以及可能有较大的传导阻滞面积所致。相反,mXinα-/-制剂中的自动和触发节律没有受到损害,可能是因为这些节律背后的机制不涉及细胞到细胞的传导。
We have previously shown that left atrial-pulmonary vein tissue (LA-PV) can generate reentrant arrhythmias (atrial fibrillation, AF) in wild-type (mXinα+/+) but not in mXinα-null (mXinα-/-) mice. With the present experiments, we investigated the arrhythmogenic activity and the underlying mechanisms in mXinα+/+ versus mXinα-/- LA-PV. Electrical activity and conduction velocity (CV) were recorded in LA-PV by means of a MED64 system. CV was significantly faster in mXinα+/+ than in mXinα-/- LA-PV and it was increased by 1 μM isoproterenol (ISO). AF could be induced by fast pacing in the mXinα+/+ but not in mXinα-/- LA-PV where automatic rhythms could be present. ISO increased the incidence of AF in Xinα+/+ whereas it increased that of automatic rhythms in mXinα-/- LA-PV. In LA-PV with the right-atrium attached (RA-LA-PV), automatic rhythms occurred in all preparations. In mXinα+/+ RA-LV-PV simultaneously treated with ISO, strophanthidin and atropine, the incidence of the automatic rhythm was about the same, but AF increased significantly. In contrast, in mXinα-/- RA-LA-PV under the same condition, the automatic rhythm was markedly enhanced, but still no AF occurred. Conventional microelectrode techniques showed a longer APD90 and a less negative maximum diastolic potential (MDP) in mXinα-/- than mXinα+/+ LA-PV tissues. Whole-cell current clamp experiments also showed a less negative MDP in mXinα-/- versus mXinα+/+ LA-PV cardiomyocytes. The fact that AF could be induced by fast pacing under several conditions in mXinα+/+ but not in mXinα-/- LA-PV preparations appears to be due to a slower CV, a prolonged APD90, a less negative MDP and possibly larger areas of conduction block in mXinα-/- myocardial cells. In contrast, the non-impairment of automatic and triggered rhythms in mXinα-/- preparations may be due to the fact that the mechanisms underlying these rhythms do not involve cell to cell conduction.
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