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Platelet dynamics in natural and pharmacologically induced hibernation

Title:  Platelet dynamics in natural and pharmacologically induced hibernation.
Investigator:  EL de Vrij
Promotor:  RH Henning
Co-promoter(es):   HR Bouma
Summary:  Blood platelets serve primarily to initiate hemostasis following blood vessel injury. In addition to a myriad of other processes, platelets are also involved in the pathogenesis of thrombo-embolic processes and inflammatory responses.

Cardiopulmonary bypass (CPB) is a commonly used technique that allows cardiac surgery under cardiac arrest. We hypothesize that inappropriate activation of platelets plays a significant role in the pathogenesis of renal injury following CPB. Platelet activation results in a widespread activation of the hemostatic system, associated with postoperative coagulation defects and organ dysfunction. Likely, platelets are involved in the pathogenesis of organ injury through formation of emboli and amplification of the inflammatory response.

Prevention of platelet activation might reduce post-operative morbidity and mortality following CPB. Mammalian hibernation, divided in periods of torpor and arousal, might yield new tools to prevent organ dysfunction and postoperative bleeding time in CPB patients. Despite the potential procoagulant state of hibernation due to hypothermia, low blood flow, increased blood viscosity, immobility, hypoxia and repetitive cooling and rewarming, no signs of platelet activation or organ injury can be found. The experiments proposed in this research investigate the changes in coagulation during hibernation, specifically focusing on platelet count and function, and the applicability in a CPB model.

In this research we intend to identify the underlying mechanisms in hibernators that prevent thrombo-embolic processes, and to exploit these mechanisms in CPB. We propose to characterize platelet amounts, function and localization during hibernation (torpor and arousal) and to assess whether platelet function is affected by temperature-independent factors including H2S. Finally, we aim to assess whether pharmacologically induced thrombocytopenia protects from organ damage during cardiopulmonary bypass (CPB).

Financing:  Junior Scientific Masterclass, MD/PhD bursary, de Cock Foundation
Start:  1-11-2013
End:  1-11-2016 
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