Circulating annexin V positive microparticles in patients after successful cardiopulmonary resuscitation.
BACKGROUND
Ischemia/reperfusion after cardiopulmonary resuscitation (CPR) induces systemic inflammatory response and activation of endothelium and coagulation, resulting in a post-cardiac arrest syndrome. We analysed circulating (annexin V+) microparticles and their conjugates in resuscitated patients.


METHODS
36 patients after successful resuscitation, 20 control patients with stable cardiac disease and 15 healthy subjects were included prospectively. Two blood samples were drawn, one immediately and one 24 hours after return of spontaneous circulation (ROSC) to detect (annexin V+) monocyte-derived microparticles (MMPs) or procoagulant (annexin V+) platelet-derived microparticles (PMPs) and conjugates of endothelial-derived (annexin V+) microparticles (EMPs) with monocytes (EMP-MC) or platelets (EMP-PC). Measurements were performed by flow cytometric analysis. Additionally, the effect of isolated microparticles on cultured endothelial cells was assessed by ELISA.


RESULTS
MMPs were significantly elevated immediately after ROSC compared to the cardiological control group (control; p < 0.01) and healthy subjects (healthy; p < 0.05) and persisted to be elevated in the following 24 hours after CPR (p < 0.05 vs. control and healthy, respectively). Procoagulant PMPs increased within the first 24 hours after ROSC (p < 0.01 vs. control and p < 0.005 vs. healthy). Conjugates of EMP with monocytes and platelets were both significantly elevated immediately after CPR (EMP-MC: p < 0.05 vs. control and p < 0.05 vs. healthy; EMP-PC: p < 0.05 vs. control and p < 0.05 vs. healthy), while only EMP-MC showed persisting high levels within 24 hours after CPR (p < 0.05 vs. control and p < 0.01 vs. healthy). MMP levels of ≥ 1.0/μL 24 hours after CPR predicted adverse outcome at 20 days (p < 0.05). Furthermore, isolated microparticles circulating in CPR patients early after ROSC led to enhanced endothelial apoptosis ex vivo compared to those of the healthy controls (p < 0.005).


CONCLUSIONS
Resuscitated patients show substantially increased levels of different (annexin V+) microparticles and their conjugates immediately and 24 hours after cardiopulmonary resuscitation, suggesting an early onset of inflammation, an ongoing endothelial activation and a procoagulatory state. Additionally, microparticles of CPR patients may contribute to endothelial apoptosis. These results point to an involvement of microparticles in the development of the post-cardiac arrest syndrome.
Department of Cardiology and Angiology, University Hospital of Freiburg, Hugstetter Str. 55, 79106 Freiburg im Breisgau, Germany. katrin.fink@uniklinik-freiburg.de
Katrin
K
Fink
Linda
L
Feldbrügge
Meike
M
Schwarz
Natascha
N
Bourgeois
Thomas
T
Helbing
Christoph
C
Bode
Tilmann
T
Schwab
Hans-Jörg
HJ
Busch
D000368:Aged; D017304:Annexin A5 / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D016887:Cardiopulmonary Resuscitation; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005260:Female; D006323:Heart Arrest / Q000150:complications / Q000628:therapy; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D017304:Annexin A5