Tani M, Neely J R
Department of Geriatrics, Keio University School of Medicine, Tokyo, Japan.
Basic Res Cardiol. 1991 Jul-Aug;86(4):340-54. doi: 10.1007/BF02191531.
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 mumol/g dry weight (dwt). During reperfusion, Nai declined rapidly (at 10 min of reperfusion: 48 mumol/g dwt, at 30 min: 25 mumol/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 mumol/g dwt after 30 min of reperfusion. Ventricular function recovered by 45%. A 10-min perfusion with 10 or 50 microM of ouabain increased Nai (17 to 21 or 27 mumol/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 mumol/g dwt, at 30 min: 32 or 40 mumol/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 mumol/g dwt, and function recovered only 35% or 28%. When high perfusate [K+] was combined with ouabain during reperfusion, the retarded decline in Nai, augmented 45Ca2+ 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 Nai and potentiation of Ca2+ overload.
在最初的再循环灌注后，将离体大鼠心脏进行25分钟的缺血处理，随后进行30分钟的再灌注。在一些心脏中，在再灌注的最初10分钟内进行了包括给予哇巴因和/或在缓冲液中加入高浓度[K⁺]在内的干预措施。在缺血期间，细胞内Na⁺（Nai）从15微摩尔/克干重增加到64微摩尔/克干重。在再灌注期间，Nai迅速下降（再灌注10分钟时：48微摩尔/克干重，30分钟时：25微摩尔/克干重），并且在再灌注期间未进行任何干预的心脏中，10分钟内恢复了正常节律。再灌注30分钟后，⁴⁵Ca²⁺摄取量从0.8微摩尔/克干重增加到7.5微摩尔/克干重。心室功能恢复了45%。用10或50微摩尔的哇巴因进行10分钟灌注会使Nai增加（分别增加到17至21或27微摩尔/克干重），同时左心室（LV）收缩功能增强，但在非缺血心脏中，高灌注液[K⁺]（20毫摩尔）联合使用可逆转这些作用。用哇巴因进行10分钟再灌注会延缓或阻止Nai的下降（再灌注10分钟时：54或63微摩尔/克干重，30分钟时：32或40微摩尔/克干重）。这些剂量的哇巴因还会使再灌注期间室性心律失常的发生率增加到30%或50%，并使心室颤动的持续时间从6.5分钟增加到11.5或18.0分钟。⁴⁵Ca²⁺摄取量达到8.8或10.0微摩尔/克干重，功能仅恢复35%或28%。当在再灌注期间高灌注液[K⁺]与哇巴因联合使用时，单独使用哇巴因引起的Nai下降延缓、⁴⁵Ca²⁺摄取增加以及功能恢复降低的情况会减弱。这些结果表明，洋地黄通过抑制先前升高的Nai的快速主动外向转运和增强Ca²⁺超载，对再灌注的缺血心脏具有毒性作用。
