Oral Presentation Australasian Extracellular Vesicles Conference 2018

Enhanced fibrinolysis and altered extracellular vesicles after remote ischaemic preconditioning in non-diabetic coronary artery disease patients (#37)

Caroline J Reddel 1 , Jerrett K Lau 1 2 , Gabrielle J Pennings 1 , Vivien M Chen 1 , Leonard Kritharides 1 2
  1. ANZAC Research Institute, CONCORD, NEW SOUTH WALES, Australia
  2. Department of Cardiology, Concord Repatriation General Hospital, Concord, NSW, Australia

Aim. Brief non-harmful ischaemia, remote ischaemic preconditioning (RIPC) has been shown to confer benefit to patients with coronary artery disease (CAD). Some studies indicate lesser benefit in patients with diabetes1. RIPC may enhance fibrinolysis2,3.

Hypothesis: RIPC causes an increase in fibrinolytic potential through release of fibrinolytic factors from the endothelium or fibrinolysis-supporting extracellular vesicles (EV) and this effect is less evident in patients with diabetes.

Method. Patients at Concord Hospital with suspected CAD were administered RIPC (sphygmomanometer on the arm, 3x5 min cycles, n=37) or sham (n=29) before angiography. Blood was collected pre- and immediately post-RIPC/sham and platelet-free plasma generated. Global coagulation/fibrinolytic potential was measured by overall haemostatic potential assay4 and various fibrinolytic factors by ELISA. EV were assessed by flow cytometry5 using surface markers for phosphatidylserine, platelets (CD41a, CD61, CD62P), leukocytes (CD45), monocytes (CD14), MAC-1 (CD11b), endothelial cells (CD144) and erythrocytes (CD235a). Positive events were defined with supernatant of ultracentrifuged pooled normal plasma as negative control. Changes pre-post RIPC were assessed by paired t-test.

Result. In the whole population there was no effect of RIPC on fibrinolytic factors or concentrations of EV. However, in non-diabetic patients, RIPC increased overall fibrinolytic potential and leukocyte-derived EV and decreased platelet-derived EV. These effects were not seen after sham treatment. The effects of RIPC were not seen in patients with diabetes mellitus.

Conclusion. There is a global increase in fibrinolytic potential after RIPC treatment in patients without diabetes mellitus, which may be contributed to by increased leukocyte-derived EV and/or decreased platelet-derived EV.

  1. Moretti C, Cerrato E, Cavallero E, Lin S, Rossi ML, Picchi A, et al. The EUROpean and Chinese cardiac and renal Remote Ischemic Preconditioning Study (EURO-CRIPS CardioGroup I): A randomized controlled trial. Int J Cardiol. 2018; 257: 1-6.
  2. Meng R, Ding Y, Asmaro K, Brogan D, Meng L, Sui M, et al. Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment. Neurotherapeutics. 2015; 12(3): 667-77.
  3. Kristiansen J, Grove EL, Rise N, Neergaard-Petersen S, Wurtz M, Kristensen SD, et al. Effect of remote ischaemic conditioning on coagulation and fibrinolysis. Thromb Res. 2016; 141: 129-35.
  4. Reddel CJ, Curnow JL, Voitl J, Rosenov A, Pennings GJ, Morel-Kopp MC, et al. Detection of hypofibrinolysis in stable coronary artery disease using the overall haemostatic potential assay. Thromb Res. 2013; 131(5): 457-62.
  5. Reddel CJ, Pennings GJ, Curnow JL, Chen VM, Kritharides L. Procoagulant Effects of Low-Level Platelet Activation and Its Inhibition by Colchicine. Thromb Haemost. 2018; 118(4): 723-33.