These results indicate early endothelial damage and ongoing endothelial dysfunction detected by elevated CECs and EMPs in resuscitated worldwide distributors patients compared with control groups. Furthermore, numbers of EPCs increased on the second day after ROSC, which points to an early initiation of endothelial regeneration. The direct comparison with patients with stable CAD undergoing coronary intervention excluded effects possibly caused by CAD or coronary intervention.In this study we could also demonstrate a significant positive correlation between the CEC count and the duration of CPR. In the literature, a long period of ischemia and longer duration of resuscitation efforts are associated with poor outcome [27,28], and the timing of the ischemic insult and the length of the reperfusion have been shown to correlate with endothelial dysfunction variables and biochemical or histological evidence for cellular damage [25,29].

Therefore, the correlation described in this study might reflect a greater extent of endothelial damage occurring during longer periods of CPR. However, we have to state that this positive correlation is largely due to a small number of patients with a long duration of CPR with CEC values outside the data cloud.After cardiac arrest and mechanical resuscitation, there is growing evidence for an ischemia and reperfusion syndrome resulting in several inflammation cascades, including activation of leucocytes [30], up-regulation of selectins [4,6], and adhesion molecules [5,31] on the surface of the endothelium.

Adrie and colleagues reported a ‘sepsis-like syndrome’ after resuscitation, with an increase in circulating interleukins, TNF, and a generalized systemic inflammatory response [3]. Researchers recently stated that an early toll-like receptor 4-induced vascular injury might be an important trigger of the systemic inflammatory response in resuscitated mice [32]. In analogy to the data obtained in our study, there are reports of elevated numbers of CECs in critically ill patients presenting with acute respiratory distress syndrome [33] and severe inflammatory disease conditions such as septic shock [34]. Hence, we excluded patients with septic shock from the study. The relatively few patients in the study with in-hospital arrests and the high percentage of patients with cardiac-related arrest suggest that most patients were not critically ill prior to cardiac arrest.

Moreover, in critically ill patients, who did not undergo CPR, CEC counts were only slightly elevated (comparable with the levels of the CAD group; data not shown). Therefore, it seems to be unlikely that critical illness or ICU procedures themselves contribute to the elevation of CECs. The currently available data does not allow for a clear differentiation Brefeldin_A of whether the increase of CECs is the cause or effect of the inflammatory reaction taking place.