Kobayashi S, Tadokoro H, Wakida Y, Kar S, Nordlander R, Haendchen R V, Corday E
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
J Am Coll Cardiol. 1991 Aug;18(2):621-7. doi: 10.1016/0735-1097(91)90622-g.
The efficacy of coronary venous retroinfusion of the iron chelator deferoxamine was studied in 24 pentobarbital-anesthetized open chest pigs with a 60 min occlusion of the left anterior descending coronary artery followed by 3 h of reperfusion. Eight retrogradely treated pigs were given 10 mg/kg body weight of deferoxamine by way of the anterior interventricular vein and eight systemically treated pigs received the same doses of deferoxamine intravenously. Drug infusions lasted for 5 min, beginning 15 min before reperfusion. Eight control pigs received systemic intravenous saline solution. Myocardial area at risk and necrotic area were assessed by the monastral blue dye and the triphenyltetrazolium chloride staining method, respectively. There were no significant differences in hemodynamics or regional myocardial function (sonomicrometry) among the groups. Infarct size expressed as percent of risk area was 73.9 +/- 13.5% in the control group, 70.6 +/- 16.4% in the systemically treated group and 48.5 +/- 21.4% (p less than 0.05) in the retrogradely treated group. In conclusion, deferoxamine significantly reduced infarct size after coronary occlusion only when given regionally by way of the coronary vein. Because there was no significant hemodynamic effect caused by deferoxamine infusion, it is suggested that this drug prevents postischemic reperfusion injury by a direct cardioprotective effect.
在24只戊巴比妥麻醉的开胸猪身上研究了铁螯合剂去铁胺经冠状静脉逆行输注的疗效。这些猪左前降支冠状动脉闭塞60分钟,随后再灌注3小时。8只经逆行治疗的猪通过室间前静脉给予10mg/kg体重的去铁胺,8只经全身治疗的猪静脉注射相同剂量的去铁胺。药物输注持续5分钟,在再灌注前15分钟开始。8只对照猪接受全身静脉生理盐水溶液。分别采用单星蓝染料法和氯化三苯基四氮唑染色法评估心肌危险区和坏死区。各组之间的血流动力学或局部心肌功能(超声心动图)无显著差异。以危险区百分比表示的梗死面积在对照组为73.9±13.5%,全身治疗组为70.6±16.4%,逆行治疗组为48.5±21.4%(p<0.05)。总之,去铁胺仅在通过冠状静脉局部给药时,才能显著减小冠状动脉闭塞后的梗死面积。由于去铁胺输注未引起显著的血流动力学效应,提示该药物通过直接的心脏保护作用预防缺血后再灌注损伤。