Effects of Hibernation on Hemostasis in 13-lined Ground Squirrels

冬眠对十三行地松鼠止血的影响

• 批准号: 8227401
• 负责人: SCOTT T COOPER
• 金额: $ 30.37万
• 依托单位: UNIVERSITY OF WISCONSIN LA CROSSE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-07 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8227401
• 关键词: Animal Model; Animals; Arousal; Back; Binding; Biological Assay; Blood; Blood Circulation; Blood Clot; Blood Platelets; Blood coagulation; Blood flow; Body Temperature; Cardiovascular system; Cell physiology; Cells; Chills; Coagulation Process; Complex; Cryopreservation; DNA; Drops; Environment; Factor IX; Factor VIII; Fibrinolysis; Genetic Transcription; Goals; Heart; Heart Rate; Hemophilia B; Hemostatic Agents; Hemostatic function; Hibernation; Hour; Human; Implant; In Vitro; Label; Lead; Lesion; Liver; Location; Mammals; Measures; Medical; Methodology; Mus; Organ; Patients; Physiological; Physiological Adaptation; Plasma Proteins; Productivity; Publications; Regulation; Research; Resistance; Risk; Role; Spermophilus; Spleen; Staging; Stress; Stroke; Students; Techniques; Telemetry; Temperature; Thrombosis; Thrombus; cold temperature; deep vein; direct application; expectation; extracellular; in vivo; induced hypothermia; neutrophil; novel; prevent; research study; response; sensor; uptake; von Willebrand Disease; von Willebrand Factor; warm temperature

DESCRIPTION (provided by applicant): Hibernating ground squirrels have dramatically decreased heart rates (3-5 beats per minute) and blood flow, which should put them at risk of forming blood clots. In response, they have several adaptations during hibernation that prevent blood clotting, including 3-fold decreases in Factors VIII (FVIII) and IX (FIX), and 10-fold decreases in von Willebrand factor (vWF), neutrophils, and platelets. The specific aims of this proposal are to study the effects of hibernation on platelet activity, formation of deep vein thrombi (DVT), and activation of fibrinolysis. By implanting ground squirrels with telemetry sensors, we will be able to determine when animals are in the five stages of hibernation: non-hibernating, entering hibernation, hibernating, interbout arousal, and emerging from hibernation. During hibernation, platelets are stored in the spleen at temperatures of 4-80C for up to six months. Within two hours of arousal in the spring, platelet levels return to normal and do not appear to be cleared rapidly. In contrast, human platelets that are stored in the cold are rapidly cleared by the liver when re-injected back into a patient. Ground squirrels will be transfused with platelets from non-hibernating and recently aroused animals, as well as platelets stored at warm or cold temperatures, to determine their rate and location of clearance in vivo. Extracellular traps, or DNA nets, from neutrophils have been detected in DVT, suggesting a protective role in the decrease of neutrophils as well. The activity of platelets and neutrophils isolated at all five stages of the hibernation cycle will be measured. These results could have direct application in extending storage of human platelets in the cold and preventing DVT. Finally, hibernation appears to increase fibrinolysis, which could help break down any clots that do form under low flow conditions. Understanding of how a ground squirrel can adapt to extreme physiological stresses on their cardiovascular system may lead to medical advances to prevent DVT, store human platelets in the cold, and regulate blood coagulation in cases of accidental or induced hypothermia. PUBLIC HEALTH RELEVANCE: This research may lead to medical advances to prevent blood clots, store human platelets in the cold, regulate blood clotting in cases of accidental or induced hypothermia, and treat hemophilia B or von Willebrand disease.

描述（由申请人提供）：冬眠的地松鼠的心率（每分钟3 - 5次）和血流量急剧下降，这应该使它们有形成血栓的风险。作为回应，它们在冬眠期间有几种适应性变化，防止血液凝固，包括因子VIII（FVIII）和IX（FIX）减少3倍，血管性血友病因子（vWF）减少10倍，中性粒细胞和血小板。这项建议的具体目标是研究冬眠对血小板活性、深静脉血栓（DVT）形成和纤溶激活的影响。通过给地松鼠植入遥测传感器，我们将能够确定动物何时处于冬眠的五个阶段：非冬眠、进入冬眠、冬眠、间歇觉醒和从冬眠中醒来。在冬眠期间，血小板在4 - 80 ℃的温度下储存在脾脏中长达六个月。在春季觉醒的两小时内，血小板水平恢复正常，似乎不会迅速清除。相比之下，储存在寒冷中的人类血小板在重新注射回患者体内时会迅速被肝脏清除。地松鼠将输注来自非冬眠和最近唤醒的动物的血小板，以及储存在温暖或寒冷温度下的血小板，以确定它们在体内的清除率和位置。已在DVT中检测到来自中性粒细胞的细胞外陷阱或DNA网，这表明在中性粒细胞减少中也具有保护作用。将测量在冬眠周期的所有五个阶段分离的血小板和中性粒细胞的活性。这些结果可以直接应用于延长人血小板在低温下的储存和预防DVT。最后，冬眠似乎增加了纤维蛋白溶解，这可能有助于分解在低流量条件下形成的任何凝块。了解地松鼠如何适应其心血管系统的极端生理压力可能会导致医学进步，以防止DVT，在寒冷中储存人类血小板，并在意外或诱导性体温过低的情况下调节血液凝固。 公共卫生相关性：这项研究可能会导致医学进步，以防止血液凝块，在寒冷中储存人类血小板，在意外或诱导体温过低的情况下调节血液凝固，以及治疗血友病B或血管性血友病。