![]() ![]() These elongated platelets are then sequestered in the spleen of the torpid ground squirrel. The thrombocytopenia is caused by an organizational change in the platelet's band of circumferential microtubules (MT), resulting in the formation of elongated rods that distort the shape of the platelet ( 13). However, during torpor their blood clotting times are prolonged by a 70% decrease in Factors VIII and IX and a 90% drop in platelet and leukocyte levels ( 9, 12). Ground squirrels are rodents about the size of rats, and have clotting times similar to those of rats and mice when in their normothermic nonhibernating state. Ground squirrels are able to survive 5 mo of hibernation, with 10–20 cycles of torpor and interbout arousal without forming lethal clots ( 9, 13, 26). These periods of torpor are interrupted by short interbout arousals during which body temperatures return to 37☌ for 12–24 h before entering the next phase of torpor. Hibernation consists of extended bouts of torpor lasting from days to weeks during which time body temperatures drop to 4–8☌ and heart rates drop down to 3–5 beats/min. ![]() To survive in extreme environments, hibernating mammals such as 13-lined ground squirrels ( Ictidomys tridecemlineatus), hereafter referred to as ground squirrels, have developed profound physiological adaptations. Identifying a model organism that can store its platelets in the cold without developing platelet storage lesions would be very helpful in identifying mechanisms to allow human platelets to be stored in the cold. However, the authors note that proper functioning of these chemically modified platelets in hemostasis is questionable ( 25). Human platelets infused with trehalose, freeze dried and rehydrated, retained some function. Cells from organisms that undergo cold desiccating conditions often infuse their cells with cryoprotectants such as the sugar trehalose ( 6). Many other cold-induced structural and functional changes occur in human platelets, leading to increased aggregation and degranulation upon warming ( 22). Two potential mechanisms of this clearance involve a clustering of von Willebrand factor (vWF) receptors (GPIbα-V-IX complex) on the surface of the platelets, followed by clearance through binding of platelet GPIbα to complement type 3 receptors (CR3) on Kupffer cells (hepatic macrophages) ( 8) or clearance by lectin receptors on hepatocytes ( 14, 15). ![]() Human, baboon, and mouse platelets that are cooled even briefly to 4☌ and then transfused are rapidly cleared, negating any benefit of storage in the cold ( 2, 4, 10, 21). Because of cold-induced platelet storage lesions ( 18, 20), platelets must stored at 22☌ with only a 5-day shelf life to avoid bacterial contamination ( 7). ![]() In 2006, over 4 million units of platelets were processed for transfusions in the United States, of which 15% expired before they could be used ( 23). Elucidating these adaptations could lead to the development of methods to store human platelets in the cold, extending their shelf life. Our results demonstrate that ground squirrel platelets appear to be resistant to the platelet cold storage lesions observed in other mammals, allowing prolonged storage in cold stasis and preventing rapid clearance upon spring arousal. Transfusion of autologous platelets stored at 4☌ or 37☌ showed the same clearance rates in ground squirrels, whereas rat platelets stored in the cold had a 140-fold increase in clearance rate. These released platelets were capable of forming stable clots and remained in circulation for at least 2 days before newly synthesized platelets were detected. Here we show that ground squirrel platelets stored in vivo at 4–8☌ were released back into the blood within 2 h of arousal in the spring with a body temperature of 37☌ but were not rapidly cleared from circulation. Upon arousal in the spring, these ground squirrels must be able to quickly restore normal clotting activity to avoid bleeding. During hibernation, 13-lined ground squirrels ( Ictidomys tridecemlineatus) must suppress hemostasis to survive prolonged body temperatures of 4–8☌ and 3–5 heartbeats per minute without forming lethal clots. Hibernating mammals have developed many physiological adaptations to extreme environments. ![]()
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