Effect of long-term remote ischaemic conditioning on platelet function and fibrinolysis in patients with chronic ischaemic heart failure.
BACKGROUND
Remote ischaemic conditioning (RIC) protects against ischaemia-reperfusion injury through cellular protective pathways, but may also modulate haemostasis. We aimed to investigate the effect of long-term RIC on platelet function and fibrinolysis in patients with chronic ischaemic heart failure (CIHF).


METHODS
In a prospective, outcome-assessor blinded, paired study, 16 patients with CIHF and 21 age- and gender-matched controls without ischaemic heart disease (IHD) were treated with RIC once daily for 28±4days. RIC was performed as four cycles of 5min upper arm ischaemia and reperfusion. We evaluated collagen and arachidonic acid induced platelet aggregation (Multiplate® Analyzer), platelet turnover (Sysmex® XE-5000), platelet activation (plasma soluble-platelet-selectin) and fibrinolysis (clot lysis time, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1)). We compared blood samples assessed at baseline and following long-term RIC.


RESULTS
Long-term RIC did not affect platelet aggregation, turnover or activation or PAI-1 in any study groups. Long-term RIC did not affect fibrin clot lysis time in patients with CIHF but reduced fibrin clot lysis time in matched controls without IHD (median: 773s (interquartile range: 689-936) vs. 658s (618-823), p=0.03). t-PA was increased following long-term RIC in CIHF patients (2.5 (1.7-3.4) vs. 2.9 (1.8-4.0), p=0.03) and in matched controls without IHD (1.5 (1.3-1.9) vs. 1.6 (1.4-2.3), p=0.03).


CONCLUSIONS
While long-term RIC did not affect collagen or arachidonic acid induced platelet aggregation, platelet turnover or sP-selectin, fibrinolysis was increased although most consistently in matched controls without IHD. This finding suggests that RIC may stimulate fibrinolysis potentially reducing the risk of thrombosis.
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Kasper
K
Pryds
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Centre for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Jacobina
J
Kristiansen
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Søs
S
Neergaard-Petersen
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Roni R
RR
Nielsen
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Michael R
MR
Schmidt
Department of Cardiology, Viborg Region Hospital, Regional Hospital Central Jutland, Viborg, Denmark.
Jens
J
Refsgaard
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Steen D
SD
Kristensen
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Hans Erik
HE
Bøtker
Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark; Centre for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Anne-Mette
AM
Hvas
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; Faculty of Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. Electronic address: erikgrove@dadlnet.dk.
Erik L
EL
Grove
D000368:Aged; D001792:Blood Platelets / Q000473:pathology*; D002908:Chronic Disease; D005260:Female; D005342:Fibrinolysis; D006333:Heart Failure / Q000097:blood / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D019007:P-Selectin / Q000097:blood; D010974:Platelet Aggregation; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000517:prevention & control; D016896:Treatment Outcome
D019007:P-Selectin
Chronic heart failure; Fibrinolysis; Haemostasis; Ischemic heart disease; Platelet function; Remote ischemic conditioning