Deleterious effects of digitalis on reperfusion-induced arrhythmias and myocardial injury in ischemic rat hearts: possible involvements of myocardial Na+ and Ca2+ imbalance.
Deleterious effects of digitalis on reperfusion-induced arrhythmias and myocardial injury in ischemic rat hearts: possible involvements of myocardial Na+ and Ca2+ imbalance.
复制标题
洋地黄对缺血大鼠心脏再灌注诱发的心律失常和心肌损伤的有害作用：可能涉及心肌 Na 和 Ca2 失衡。
DOI：
10.1007/bf02191531
复制
发表时间：
1991
影响因子：
9.5
通讯作者：
Neely,JR
中科院分区：
文献类型：
--
作者：
Tani,M;Neely,JR
在初始再循环灌注后，使离体大鼠心脏缺血25分钟，然后再灌注30分钟。在某些心脏中，在再灌注的前10分钟进行干预，包括给予哇巴因和/或高[K+]缓冲液，在缺血期间，细胞内Na+（Nai）从15 μmol/g干重（dwt）增加到64 μmol/g干重（dwt）。再灌注10 min时，Na+迅速下降（48 μ mol/g dwt，30 min时为25 μ mol/g dwt），心律在10 min内恢复正常，再灌注30 min时45 Ca ~（2+）摄取由0.8 μ mol/g dwt增加到7.5 μmol/g dwt。心室功能恢复45%，10或50 μM哇巴因灌注10分钟可增加Nai（17至21或27 μmol/g dwt），左心室（LV）收缩功能增加，但在非缺血心脏中，高灌注液[K+]（20 mM）可逆转这些作用，哇巴因再灌注10 min可延迟或停止Nai的下降，（再灌注10 min：54或63 μmol/g dwt，30 min：32或40 μmol/g dwt）。哇巴因还使再灌注期室性心律失常的发生率增加到30%或50%，室颤持续时间从6.5分钟增加到11.5或18.0分钟。45 Ca ~（2+）摄取量达到8.8或10.0 μmol/g dwt，功能恢复仅为35%或28%。在再灌注过程中，高灌流液[K+]与哇巴因合用，可减轻单独哇巴因引起的Nai下降、45 Ca ~（2+）摄取增加和功能恢复减慢。这些结果表明，洋地黄对再灌注缺血心脏的毒性作用，通过抑制先前升高的Na+的快速主动向外转运和增强Ca ~（2+）超载。
Isolated rat hearts were made ischemic for 25 min after an initial recirculating perfusion, followed by 30 min of reperfusion. In some hearts, interventions including administration of ouabain and/or high [K+] in the buffer were performed during the first 10 min of reperfusion.During ischemia, intracellular Na+(Nai) increased from 15 to 64 [μmol/g dry weight (dwt). During reperfusion, Naideclined rapidly (at 10 min of reperfusion: 48 μnol/g dwt, at 30 min: 25 μ mol/g dwt) and regular rhythm was recovered within 10 min in hearts without any intervention during reperfusion.45Ca2+uptake increased from 0.8 to 7.5 μmol/g dwt after 30 min of reperfusion. Ventricular function recovered by 45 %.A 10-min perfusion with 10 or 50 μM of ouabain increased Nai(17 to 21 or 27 μmol/g dwt) with increased left-ventricular (LV) contractile function, but these effects were reversed by combination of high perfusate [K+] (20 mM) in non-ischemic hearts.A 10-min reperfusion with ouabain retarded or stopped the decline in Nai(at 10 min of reperfusion: 54 or 63 μmol/g dwt, at 30 min: 32 or 40 μmol/g dwt). These amounts of ouabain also increased the incidence of ventricular tachyarrhythmias during reperfusion to 30 % or 50 %, and increased the duration of ventricular fibrillation from 6.5 to 11.5 or 18.0 min.45Ca2+uptake reached to 8.8 or 10.0 μmol/g dwt, and function recovered only 35 % or 28 %. When high perfusate [K+] was combined with ouabain during reperfusion, the retarded decline in Nai, augmented45Ca2+uptake, and reduced recovery of function caused by ouabain alone were attenuated. These results suggest that digitalis has toxic effects on reperfused ischemic hearts by inhibition of rapid active outward transport of previously elevated Naiand potentiation of Ca2+overload.