Platelet dynamics during natural and pharmacologically induced torpor and forced hypothermia.
Hibernation is an energy-conserving behavior in winter characterized by two phases: torpor and arousal. During torpor, markedly reduced metabolic activity results in inactivity and decreased body temperature. Arousal periods intersperse the torpor bouts and feature increased metabolism and euthermic body temperature. Alterations in physiological parameters, such as suppression of hemostasis, are thought to allow hibernators to survive periods of torpor and arousal without organ injury. While the state of torpor is potentially procoagulant, due to low blood flow, increased viscosity, immobility, hypoxia, and low body temperature, organ injury due to thromboembolism is absent. To investigate platelet dynamics during hibernation, we measured platelet count and function during and after natural torpor, pharmacologically induced torpor and forced hypothermia. Splenectomies were performed to unravel potential storage sites of platelets during torpor. Here we show that decreasing body temperature drives thrombocytopenia during torpor in hamster with maintained functionality of circulating platelets. Interestingly, hamster platelets during torpor do not express P-selectin, but expression is induced by treatment with ADP. Platelet count rapidly restores during arousal and rewarming. Platelet dynamics in hibernation are not affected by splenectomy before or during torpor. Reversible thrombocytopenia was also induced by forced hypothermia in both hibernating (hamster) and non-hibernating (rat and mouse) species without changing platelet function. Pharmacological torpor induced by injection of 5'-AMP in mice did not induce thrombocytopenia, possibly because 5'-AMP inhibits platelet function. The rapidness of changes in the numbers of circulating platelets, as well as marginal changes in immature platelet fractions upon arousal, strongly suggest that storage-and-release underlies the reversible thrombocytopenia during natural torpor. Possibly, margination of platelets, dependent on intrinsic platelet functionality, governs clearance of circulating platelets during torpor.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Edwin L
EL
de Vrij
Sulfateq BV, Groningen, the Netherlands.
Pieter C
PC
Vogelaar
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Maaike
M
Goris
Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Martin C
MC
Houwertjes
Zoological Institute, University of Hamburg, Hamburg, Germany.
Annika
A
Herwig
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
George J
GJ
Dugbartey
Department of Chronobiology, University of Groningen, Center for Behaviour & Neurosciences, Groningen, The Netherlands; Department of Molecular Neurobiology, University of Groningen, Center for Behavior & Neurosciences, Groningen, The Netherlands; Department of Nuclear Medicine & Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Ate S
AS
Boerema
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Chronobiology, University of Groningen, Center for Behaviour & Neurosciences, Groningen, The Netherlands.
Arjen M
AM
Strijkstra
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Hjalmar R
HR
Bouma
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Robert H
RH
Henning
D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D001143:Arousal / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology*; D001831:Body Temperature; D006224:Cricetinae; D005260:Female; D006605:Hibernation; D007036:Hypothermia, Induced; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012621:Seasons; D013921:Thrombocytopenia / Q000503:physiopathology; D013997:Time Factors; D064348:Torpor
D019007:P-Selectin; D000244:Adenosine Diphosphate