In contrast, Zingarelli et al. found that ant-TNF-α antibodies improved survival in an extremely severe paradigm of hemorrhagic shock in rats (death by 30 minutes post-hemorrhage) [38].
At a dose similar to those used in most preconditioning studies (26 mg/kg i.p ., post-hemorrhage treatment with hemin reduced parenchymal extravasation of Evans blue by about three-quarters in both the blood injection and collagenase ICH models.
Statistically significant elevations vs. baseline in TNF-α were observed at 60 min (223±52 pg/ml) and 90 min (239±51 pg/ml) post-hemorrhage (Fig. 7A).
In survivors, mean serum TNF-α at baseline was 77±7 pg/ml, rose in a statistically significant fashion following the initial surgery, and remained elevated up to 75 min post-hemorrhage (with statistically significant changes vs. baseline at 0, 15, 30, 45, 60, and 75 min post-hemorrhage; Fig. 5A).
Ayala et al. found that IL-6 increased continuously post-hemorrhage and was already increased after midline laparotomy and before initiation of hemorrhage compared with non-manipulated animals, while TNF-α was only detected once hemorrhage was initiated [35], [41].
A statistically significant difference in circulating IL-10 was observed between survivors and non-survivors at 15 min post-surgical baseline as well as at 15 and 60 min post-hemorrhage (Fig. 5D).
A statistically significant difference in TNF-α was found between survivors and non-survivors at several experimental time points (15 min post-surgical baseline; at the start of hemorrhage [0]; and at 15, 30, 45, 60, and 75 min post-hemorrhage; Fig. 5A).
In contrast, other authors reported that inhibition of endogenous H2S synthesis attenuated post-hemorrhage organ dysfunction [ 4, 5].
These findings are particularly important as sepsis is a common complication in the post-traumatic and post-hemorrhage course.
The factors associated with ICH occurrence and post-hemorrhage survival of these patients were somewhat different from the traditionally reported risk factors for ICH.
