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Am J Transl Res. 2018 Mar 15;10(3):816-826. eCollection 2018.

No indications for platelet activation in acute clinical myocardial or renal ischemia/reperfusion injury.

American journal of translational research

Kirsten A Kortekaas, Dorottya K de Vries, Mark Roest, Marlies Ej Reinders, Eric P van der Veer, Robert Jm Klautz, Philip G de Groot, Alexander F Schaapherder, Jan H Lindeman

Affiliations

  1. Department of Cardiothoracic Surgery, Leiden University Medical CenterLeiden, The Netherlands.
  2. Department of Cardiology, OLVG OostAmsterdam, The Netherlands.
  3. Department of Surgery, Leiden University Medical CenterLeiden, The Netherlands.
  4. Department of Clinical Chemistry and Hematology, University Medical Center UtrechtUtrecht, The Netherlands.
  5. Current address: Department of Biochemistry, Cardiovascular Research Institute, Maastricht UniversityMaastricht, The Netherlands.
  6. Department of Nephrology, Leiden University Medical CenterLeiden, The Netherlands.

PMID: 29636871 PMCID: PMC5883122

Abstract

The pathophysiology of ischemia/reperfusion (I/R) injury is complex and poorly understood. Animal studies imply platelet activation as an initiator of the inflammatory response upon reperfusion. However, it remains unclear whether and how these results translate to clinical I/R. This study evaluates putative platelet activation in the context of two forms of clinical I/R (heart valve surgery with aortic-cross clamping, n = 39 and kidney transplantation, n = 34). The technique of sequential selective arteriovenous (AV) measurements over the reperfused organs was applied to exclude the influence of systemic changes occurring during surgery while simultaneously maximizing sensitivity. Platelet activation and degranulation was evaluated by assessing the expression levels of established markers, i.e. RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), β-thromboglobulin (β-TG), platelet-derived growth factor (PDGF)-BB and CXCL8 (known as interleukin-8), and by employing an in-vitro assay that specifically tests for platelet excitability. Moreover, a histological analysis was performed by means of CD41 staining. Results show stable RANTES, β-TG, PDGF-BB and CXCL8 AV-concentrations within the first half hour over the reperfused organs, suggesting that myocardial and renal I/R are not associated with platelet activation. Results from the platelet excitability assay were in line with these findings and indicated reduced and stable platelet excitability following renal and myocardial reperfusion, respectively. Histological analysis yield evidence of platelet marginalization in the reperfused organs. In conclusion, results from this study do not support a role for platelet activation in early phases of clinical I/R injury.

Keywords: Ischemia; inflammation; platelets; reperfusion

Conflict of interest statement

None.

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