Translating organ conditioning: On the use of remote ischaemia and helium

Daniel Brevoord

Research output: ThesisThesis, fully internal

Abstract

This thesis explores two promising forms of conditioning for organ protection against ischaemia and reperfusion injury: remote ischaemia and helium inhalation. We evaluated whether these methods of conditioning could be translated into clinical practice; and what the possible underlying mechanism is.
We reviewed the results of 23 different randomised clinical trials on remote ischaemic conditioning and although this reduced cardiac injury, there was no improvement in clinical outcome. In a randomised controlled trial in cardiac surgery patients we found no effect of remote ischaemic conditioning on the molecular markers ERK-1, ERK-2, STAT3 or STAT5 in myocardial tissue. Nor did we see a reduction in myocardial injury as measured by troponin T release after surgery. This was the case in patients with or without diabetes mellitus.
We demonstrated that helium conditioning prevents endothelial dysfunction in healthy volunteers after forearm ischaemia. This was not mediated by eNOS and we found no effect on the level of circulating cytokines or microparticles. In cardiac surgery patients however, we did not see an effect of helium pre- or postconditioning on ERK-1, ERK-2, p-38 mitogen-activated protein kinase or protein kinase C-epsilon activation. Nor did conditioning with helium reduce troponin T release after surgery. We demonstrated that helium can safely be administered to patients admitted to the intensive care unit after cardiac arrest and this allowed for a reduction in respiratory rate and minute volume ventilation.
Despite promising early results, neither form of conditioning protected against ischaemia and reperfusion injury in patients in a clinically relevant setting.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Amsterdam
Supervisors/Advisors
  • Hollmann, Markus W., Supervisor
  • Preckel, Prof. dr. , Benedikt, Supervisor
  • Hauck, Nina C., Co-supervisor
  • Horn, Johanna, Co-supervisor
  • Hollmann, W.M., Supervisor, External person
Award date28 Oct 2020
Print ISBNs9789463809856
Publication statusPublished - 2020

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