Severe endothelial injury and subsequent repair in patients after successful cardiopulmonary resuscitation.
BACKGROUND
Ischemia and reperfusion after cardiopulmonary resuscitation (CPR) induce endothelial activation and systemic inflammatory response, resulting in post-resuscitation disease. In this study we analyzed direct markers of endothelial injury, circulating endothelial cells (CECs) and endothelial microparticles (EMPs), and endothelial progenitor cells (EPCs) as a marker of endothelial repair in patients after CPR.


METHODS
First we investigated endothelial injury in 40 patients after CPR, 30 controls with stable coronary artery disease (CAD), and 9 healthy subjects, who were included to measure CECs and EMPs. In a subsequent study, endothelial repair was assessed by EPC measurement in 15 CPR, 9 CAD, and 5 healthy subjects. Blood samples were drawn immediately and 24 hours after ROSC and analyzed by flow cytometry. For all statistical analyses P < 0.05 was considered significant.


RESULTS
There was a massive rise in CEC count in resuscitated patients compared to CAD (4,494.1 +/- 1,246 versus 312.7 +/- 41 cells/mL; P < 0.001) and healthy patients (47.5 +/- 3.7 cells/mL; P < 0.0005). Patients after prolonged CPR (>or=30 min) showed elevated CECs compared to those resuscitated for <30 min (6,216.6 +/- 2,057 versus 2,340.9 +/- 703.5 cells/mL; P = 0.13/ns). There was a significant positive correlation of CEC count with duration of CPR (R2= 0.84; P < 0.01). EMPs were higher immediately after CPR compared to controls (31.2 +/- 5.8 versus 19.7 +/- 2.4 events/microL; P = 0.12 (CAD); versus 15.0 +/- 5.2 events/microL; P = 0.07 (healthy)) but did not reach significance until 24 hours after CPR (69.1 +/- 12.4 versus 22.0 +/- 3.0 events/microL; P < 0.005 (CAD); versus 15.4 +/- 4.4 events/microL; P < 0.001 (healthy)). EPCs were significantly elevated in patients on the second day after CPR compared to CAD (1.16 +/- 0.41 versus 0.02 +/- 0.01% of lymphocytes; P < 0.005) and healthy (0.04 +/- 0.01; P < 0.005).


CONCLUSIONS
In the present study we provide evidence for a severe endothelial damage after successful CPR. Our results point to an ongoing process of endothelial injury, paralleled by a subsequent endothelial regeneration 24 hours after resuscitation.
Fink
Katrin
K
Department of Cardiology and Angiology, University Hospital of Freiburg, Hugstetter Str 55, 79106 Freiburg im Breisgau, Germany. katrin.fink@uniklinik-freiburg.de
Schwarz
Meike
M
Feldbrügge
Linda
L
Sunkomat
Julia N
JN
Schwab
Tilmann
T
Bourgeois
Natascha
N
Olschewski
Manfred
M
von Zur Mühlen
Constantin
C
Bode
Christoph
C
Busch
Hans-Jörg
HJ
D000368:Aged; D015415:Biomarkers; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D055252:Cell-Derived Microparticles / Q000378:metabolism; D003324:Coronary Artery Disease / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism; D004727:Endothelium / Q000293:injuries* / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012038:Regeneration; D013234:Stem Cells / Q000378:metabolism; D015599:Trauma Severity Indices; D014945:Wound Healing / Q000502:physiology*
D015415:Biomarkers