Lindenblatt Nicole, Menger Michael D, Klar Ernst, Vollmar Brigitte
Dept. of Experimental Surgery and Dept. of General Surgery, Univ. of Rostock, Schillingallee 70, 18055 Rostock, Germany.
Am J Physiol Heart Circ Physiol. 2005 Dec;289(6):H2680-7. doi: 10.1152/ajpheart.00425.2005. Epub 2005 Aug 12.
Cold is supposed to be associated with alterations in blood coagulation and a pronounced risk for thrombosis. We studied the effect of clinically encountered systemic hypothermia on microvascular thrombosis in vivo and in vitro. Ferric chloride-induced microvascular thrombus formation was analyzed in cremaster muscle preparations from hypothermic mice. Additionally, flow cytometry and Western blot analysis was used to evaluate the effect of hypothermia on platelet activation. To test whether preceding hypothermia predisposes for enhanced thrombosis, experiments were repeated after hypothermia and rewarming to 37 degrees C. Control animals revealed complete occlusion of arterioles and venules after 742 +/- 150 and 824 +/- 172 s, respectively. Systemic hypothermia of 34 degrees C accelerated thrombus formation in arterioles and venules (279 +/- 120 and 376 +/- 121 s; P < 0.05 vs. 37 degrees C). This was further pronounced after cooling to 31 degrees C (163 +/- 57 and 281 +/- 71 s; P < 0.05 vs. 37 degrees C). Magnitude of thrombin receptor activating peptide (TRAP)-induced platelet activation increased with decreasing temperatures, as shown by 1.8- and 3.0-fold increases in mean fluorescence after PAC-1 binding to glycoprotein (GP)IIb-IIIa and 1.6- and 2.9-fold increases of fibrinogen binding on incubation at 34 degrees C and 31 degrees C. Additionally, tyrosine-specific protein phosphorylation in platelets was increased at hypothermic temperatures. In rewarmed animals, kinetics of thrombus formation were comparable to those in normothermic controls. Concomitantly, spontaneous and TRAP-enhanced GPIIb-IIIa activation did not differ between rewarmed platelets and those maintained continuously at 37 degrees C. Moderate systemic hypothermia accelerates microvascular thrombosis, which might be mediated by increased GPIIb-IIIa activation on platelets but does not cause predisposition with increased risk for microvascular thrombus formation after rewarming.
感冒被认为与血液凝固的改变以及明显的血栓形成风险有关。我们研究了临床中遇到的全身性低温对体内和体外微血管血栓形成的影响。在低温小鼠的提睾肌标本中分析了氯化铁诱导的微血管血栓形成。此外，使用流式细胞术和蛋白质印迹分析来评估低温对血小板活化的影响。为了测试先前的低温是否会导致血栓形成增强，在低温和复温至37℃后重复实验。对照动物分别在742±150秒和824±172秒后显示小动脉和小静脉完全闭塞。34℃的全身性低温加速了小动脉和小静脉中的血栓形成（分别为279±120秒和376±121秒；与37℃相比，P<0.05）。冷却至31℃后这种情况更加明显（分别为163±57秒和281±71秒；与37℃相比，P<0.05）。凝血酶受体激活肽（TRAP）诱导的血小板活化程度随着温度降低而增加，如在34℃和31℃孵育时，PAC-1与糖蛋白（GP）IIb-IIIa结合后平均荧光分别增加1.8倍和3.0倍，纤维蛋白原结合分别增加1.6倍和2.9倍所示。此外，在低温下血小板中的酪氨酸特异性蛋白磷酸化增加。在复温的动物中，血栓形成动力学与正常体温对照相当。同时，复温血小板与持续维持在37℃的血小板之间，自发和TRAP增强的GPIIb-IIIa活化没有差异。中度全身性低温会加速微血管血栓形成，这可能是由血小板上GPIIb-IIIa活化增加介导的，但不会导致复温后微血管血栓形成风险增加的易感性。
