Perdrizet George A, Lena Christopher J, Shapiro David S, Rewinski Michael J
Department of Surgery and Trauma, Hartford Hospital and University of Connecticut School of Medicine, Farmington, CT 06102-5037, USA.
J Thorac Cardiovasc Surg. 2002 Jul;124(1):162-70. doi: 10.1067/mtc.2002.122312.
All forms of surgical therapy are stressful and injurious. The problems of paralysis, renal dysfunction, and colonic ischemia associated with aortic occlusion are due to acute ischemia-reperfusion injury at the cellular level. Acute-anterior spinal cord ischemia is the most devastating outcome of these iatrogenic-ischemic events. The majority of surgical procedures are performed electively and therefore provide an opportunity to preoperatively condition the patient to minimize these ischemia-related morbidities.
We sought to determine whether acute spinal cord injury associated with aortic occlusion can be prevented by induction of the cellular stress response by means of preoperative administration of whole-body hyperthermia or stannous chloride.
The study consisted of an experimental rabbit model of infrarenal aortic occlusion for 20 minutes at normothermic body temperature.
Control rabbits experienced an 88% (7/8) incidence of paralysis after spinal cord ischemia induced by 20 minutes of aortic occlusion, whereas animals treated preoperatively with either whole-body hyperthermia (0/9) or stannous chloride (0/4) never became paralyzed (P <.001 for control vs treated groups). Ischemic protection of the spinal cord was associated with increased content of stress proteins within tissues of pretreated animals.
Prior induction of the heat shock response in the whole animal will increase the content of stress proteins within the spinal cord and other tissues and result in the prevention of hind-limb paralysis associated with aortic occlusion. We have designated the preoperative induction of the cellular stress response for the prevention of ischemic tissue injury stress conditioning. We suggest that stress-conditioning protocols represent the opportunity to practice preventative medicine at the molecular level.
所有形式的外科治疗都具有压力且会造成损伤。与主动脉阻断相关的瘫痪、肾功能障碍和结肠缺血问题,是由于细胞水平的急性缺血再灌注损伤所致。急性脊髓前动脉缺血是这些医源性缺血事件最具破坏性的后果。大多数外科手术是择期进行的,因此为术前对患者进行预处理以尽量减少这些缺血相关的发病率提供了机会。
我们试图确定术前给予全身热疗或氯化亚锡诱导细胞应激反应,是否能预防与主动脉阻断相关的急性脊髓损伤。
该研究包括一个在正常体温下肾下腹主动脉阻断20分钟的实验兔模型。
在20分钟主动脉阻断诱导脊髓缺血后,对照兔出现瘫痪的发生率为88%(7/8),而术前接受全身热疗(0/9)或氯化亚锡(0/4)治疗的动物从未出现瘫痪(对照组与治疗组比较,P<.001)。脊髓的缺血保护与预处理动物组织中应激蛋白含量增加有关。
预先在整个动物体内诱导热休克反应会增加脊髓和其他组织中应激蛋白的含量,并导致预防与主动脉阻断相关的后肢瘫痪。我们将术前诱导细胞应激反应以预防缺血性组织损伤称为应激预处理。我们认为应激预处理方案代表了在分子水平上实践预防医学的机会。