Dickson E W, Reinhardt C P, Renzi F P, Becker R C, Porcaro W A, Heard S O
University of Massachusetts Medical Center Department of Emergency Medicine, Worcester, Massachusetts 01655, USA.
J Thromb Thrombolysis. 1999 Aug;8(2):123-9. doi: 10.1023/a:1008911101951.
This research was designed to test the hypothesis that ischemic preconditioning can be transferred between animals via whole blood transfusion. Preconditioning at a distance refers to the reduction in myocardial infarct size seen when coronary artery occlusion is preceded by brief ischemic episodes of noncardiac tissue. Isolation of the trigger signal responsible for this effect may be useful in the diagnosis and treatment of acute coronary occlusive syndromes. Rabbits were paired by crossmatching blood samples prior to experimentation. Crossmatched pairs were placed into either preconditioned (P) or control sets. Rabbits in the preconditioned sets were further divided into donor (PD) and acceptor (PA) animals. PD animals underwent five episodes of circumflex and renal artery occlusion followed by reperfusion. Before and after each preconditioning episode, a whole blood exchange was performed between PD and PA animals. Alternatively, control rabbits underwent the same surgical procedures and time-sequenced transfusion without preconditioning. All animals then underwent prolonged circumflex occlusion (60 minutes) followed by reperfusion (30 minutes). The area of myocardium at risk (R) was determined by isotope-labeled microsphere injection. Infarct size (I) was determined by NBT staining. The percent infarct within the risk area (I/R) was then compared. The I/R was significantly lower in the PA (14.0% +/- 12.2) and PD (14.3% +/- 11.2) groups as compared with controls (61% +/- 20. 6). There was no significant difference between the tPA and TPD groups. In conclusion, the ischemic preconditioning effect can be transferred to nonpreconditioned animals via whole blood transfusion, suggesting a humoral mechanism for preconditioning at a distance.
本研究旨在验证缺血预处理能否通过全血输注在动物之间进行传递这一假设。远程预处理是指在冠状动脉闭塞之前,非心脏组织先经历短暂缺血发作时,心肌梗死面积会减小。分离负责这种效应的触发信号可能对急性冠状动脉闭塞综合征的诊断和治疗有用。实验前通过交叉配血将兔子配对。交叉配对的兔子被分为预处理组(P)或对照组。预处理组的兔子进一步分为供体(PD)和受体(PA)动物。PD动物经历五次冠状动脉回旋支和肾动脉闭塞再灌注。在每次预处理前后,在PD和PA动物之间进行全血交换。或者,对照兔子接受相同的外科手术和按时间顺序的输血,但不进行预处理。然后所有动物都经历长时间的冠状动脉回旋支闭塞(60分钟),随后再灌注(30分钟)。通过同位素标记微球注射确定危险心肌面积(R)。通过NBT染色确定梗死面积(I)。然后比较危险区域内的梗死百分比(I/R)。与对照组(61%±20.6)相比,PA组(14.0%±12.2)和PD组(14.3%±11.2)的I/R显著降低。tPA组和TPD组之间没有显著差异。总之,缺血预处理效应可通过全血输注传递给未预处理的动物,提示存在远程预处理的体液机制。