Abstract 2465: Neutrophil Activation and Platelet Interaction After Cardiac Arrest Resuscitation
Background: After initial resuscitation from cardiac arrest, patients suffer an ischemia-reperfusion pathophysiology that remains poorly characterized. The mechanisms for this “post-resuscitation syndrome”, and therefore potential pharmacologic targets for therapy, also remain unclear.
Objective: We hypothesized that neutrophil activation and neutrophil-platelet interaction occur in the 24 hrs after initial resuscitation.
Methods: A prospective cohort of initial arrest survivors were proxy consented and enrolled for serial blood sampling between Dec 2007 and Jan 2009 at one tertiary care hospital. Blood sampling occurred at 0, 6, 12 and 24 hrs after initial resuscitation. Neutrophil activation and neutrophil-platelet interactions were measured via fluorescent-antibody cell sorting assays, and IL-6, IL-10 and soluble TNF-alpha receptor (sTNF-aR) levels were measured via enzyme-linked immunosorbent assays. Healthy volunteers served as controls for both assays.
Results: A cohort of 16 post-arrest patients was enrolled. Mean age was 64±15, 38% were female, and 25% survived to discharge. Cell fraction with CD18+:CD41+ double-positivity, indicating activated neutrophils bound to platelets, increased from 0 hr to a peak elevation at the 6 hr timpoint (0.38±0.21 vs. 0.45±0.24 cell fraction, p=0.03) and then fell by 24 hrs. sTNF-aR levels increased throughout the 24 hr period and at each sampling this elevation was statistically significant (p=0.01) compared to the initial timepoint, while IL-6 and IL-10 remained static at clinically elevated levels. Compared to healthy control subjects, all three humoral factors (sTNF-R, IL-6, IL-10) were markedly elevated at all timepoints, consistent with prior work.
Conclusions: Neutrophil activation and interaction with platelets occurs over a clinically relevant timecourse post-resuscitation. Complexes of neutrophils-platelets may be a source of microvascular dysfunction and poor flow through microvascular beds as has been postulated in post-resuscitation syndrome.