摘要
目的研究内源性洋地黄样物质(EDLS)特异性拮抗剂地高辛抗血清对离体大鼠心脏低氧复氧性心律失常的防治作用,明确EDLS在再灌注心律失常中的作用与机制。方法制备离体大鼠心脏低氧复氧损伤模型,60只SD大鼠随机分为6组,每组10只。正常对照组给予富氧KH液(充以95%O2+5%CO2混合气体,流量10ml/min,温度37℃,压力80cmH2O)持续灌流90min;低氧复氧损伤组富氧KH液灌流30min后,予以乏氧KH液(充以95%N2+5%CO2混合气体,流量1～2ml/min)灌流30min,再给予富氧KH液复灌30min;维拉帕米组于复氧前向灌流液中加入维拉帕米(5mg/kg),复氧灌流前灌注完,其余同低氧复氧损伤组;小剂量地高辛抗血清组、中剂量地高辛抗血清组、大剂量地高辛抗血清组于复氧前分别向灌流液中加入地高辛抗血清33mg/kg、10mg/kg、30mg/kg,复氧灌流前灌注完,其余同低氧复氧损伤组。连续记录各组心电图。各组于复氧灌流结束时,测定心肌匀浆中EDLS含量、心肌细胞膜Na+K+ATP酶活性以及线粒体内Ca2+水平。结果低氧复氧损伤组于复氧灌流早期出现频发室性早搏、室性心动过速和心室颤动;心肌组织EDLS水平明显升高,心肌细胞膜Na+K+ATP酶活性明显下降,线粒体内Ca2+水平显著升高。大、中剂量地高辛抗血清能拮抗复氧引起的室性心律失常,降低心肌组织EDLS水平。
Objective To evaluate the protective effect of an endogenous digitalis like substance (EDLS) special antagonist,anti digoxin antiserum,on hypoxia reoxygenation induced arrhythmia and to clarify its mechanism Methods The isolated Langendorff perfused rat heart model was established Sprague Dawley (SD) rats were randomly divided into six groups and each group had 10 rats In the normal control group,hearts were perfused with a normal krebs Henseleit (K H) buffer (saturation 95%O 2+5%CO 2) at a constant flow (10 ml·min -1 ) with temperature of 37℃ and pressure of 80 cmH 2O for 90 min The hypoxia reoxygenation injury group experienced 30 min equilibration,30 min hypoxia with K H buffer (saturation 95%N 2+5%CO 2) at a constant flow (1～2 ml/min) and 30 min reoxygenation For the verapamil group,low,middle,high dose anti digoxin antiserum group,hearts were perfused with verapamil (5 mg/kg) or anti digoxin antiserum(3 3,10,30 mg/kg) respectively before reoxygenation,the others were same as the hypoxia reoxygenation injury group The electrocardiogram was recorded continuously The activity of Na + K + ATPase, EDLS and mitochon drial Ca 2+ contents in myocardial tissues were measured respectively Results The hypoxia reoxygenation group showed more premature ventricular beats,ventricular tachycardia and ventricular fibrillation at early stage of reoxygenation;a remarkable increase in the levels of EDLS in myocardial tissues and mitochondrial Ca 2+ ,and an obvious decrease in Na + K + ATPase activity in myocardial cell membrane Middle,high antidigoxin antiserum could antagonize the ventricular arrhythmia induced by reoxygenation,decrease the levels of EDLS in myocardial tissues and mitochondrial Ca 2+ ,and recovery the activities of Na + K + ATPase in myocardial cell membrane Conclusion Anti digoxin antiserum had an obvious protective effect on reperfusion arrhythmia Its mechanism may be related to antagonize EDLS,recovery Na + K + ATPase activity in myocardial cell membrane and relieve intracellular Ca 2+ overload The EDLS might be one of the majors factor in reoxygenation arrhythmia
出处
《中华心律失常学杂志》
2004年第5期285-289,共5页
Chinese Journal of Cardiac Arrhythmias
基金
安徽省自然科学基金项目(01043902)
安徽省教育厅自然科学基金项目(99j10219
2001kj256)
