Khatter J C, Navaratnam S, Agbanyo M
Department of Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Biochem Pharmacol. 1990 Sep 1;40(5):997-1003. doi: 10.1016/0006-2952(90)90485-4.
In the present study, arrhythmogenic toxicity of cardiac glycoside ouabain was investigated in guinea pigs after intravenous infusion (5 micrograms/kg/min). Guinea pigs of 18-24 months of age required significantly (P less than 0.05) lower doses of ouabain that 3-month-old animals (72 +/- 3 vs 100 +/- 3 micrograms/kg) for the initiation of cardiac arrhythmias. Investigation of Na(+)-Ca2+ exchange in the isolated sarcolemmal vesicles revealed a marked reduction in the Na(+)-dependent Ca2+ uptake. Kinetic analysis of these data has demonstrated a 70% reduction in Vmax and reduced affinity for Ca2+ in vesicles from 18-month-old as compared to 3-month-old guinea pigs. The rate of Na(+)-dependent Ca2+ efflux was also markedly lower in the vesicles of older animals, and the vesicles retained more Ca2+ after 3 min of Na(+)-dependent Ca2+ extrusion than did those from 3-month-old animals. The results suggest that the sensitivity to cardiac glycocide increases with age and may be associated with altered sarcolemmal Na(+)-Ca2+ exchange activity.
在本研究中，对豚鼠静脉输注（5微克/千克/分钟）强心苷哇巴因后，研究了其致心律失常毒性。18至24月龄的豚鼠引发心律失常所需的哇巴因剂量（72±3微克/千克）显著低于3月龄动物（100±3微克/千克）（P<0.05）。对分离的肌膜囊泡中Na(+)-Ca2+交换的研究表明，Na(+)依赖性Ca2+摄取显著减少。对这些数据的动力学分析表明，与3月龄豚鼠相比，18月龄豚鼠的囊泡中Vmax降低了70%，对Ca2+的亲和力降低。老龄动物囊泡中Na(+)依赖性Ca2+外流速率也显著降低，且在Na(+)依赖性Ca2+外排3分钟后，囊泡保留的Ca2+比3月龄动物的囊泡更多。结果表明，对强心苷的敏感性随年龄增加而增加，可能与肌膜Na(+)-Ca2+交换活性改变有关。
