Evaluation of hemorrhagic shock and traumatic brain injury effects on hemodynamics and metabolomics

Traumatic brain injury (TBI) is often accompanied by hemorrhage. However, treatment of hemorrhagic shock (HS) after TBI is challenging because the treatment strategies for TBI and HS often conflict. Little is known about the complex pathophysiological differences between these two traumas when happening individually or combined. The aim of the present study was to evaluate effects of HS and TBI individually and combined on hemodynamics, baroreflex and brain metabolomics. Male Wistar rats were instrumented with catheters and subjected to TBI through a pneumatic controlled cortical impact. HS was induced by blood withdrawal to achieve a blood pressure (BP) between 35-40mmHg, and this hypotensive state was maintained for 90 min. Animals were separated into 4 groups (n=5): Sham (underwent surgery, but no TBI or HS was done), HS (animals were placed in the stereotaxic, but no TBI), TBI (TBI was performed and timeline was followed as described, but no HS was done), and TBI+HS. Rats were sacrificed 90 min after HS and tissues were harvested. BP, heart rate (HR), and indices of spontaneous baroreflex sensitivity were evaluated at baseline, 10 min after TBI, and at 10 and 90 min after HS. The brain was harvested and a metabolomic analysis for tricarboxylic acid (TCA) cycle, amino acids and lipids was performed in the impacted area. BP decreased in the TBI group compared to Sham and, as expected, it severely decreased in HS and TBI+HS groups, once they were kept at lower pressure levels for 90 min. Heart Rate (HR) was lower in the HS group compared to Sham and TBI groups. It was observed that HS decreases the BP alteration events’ number during a fixed 10 min period compared to Sham and TBI groups, however the association of TBI with HS normalized this parameter. This suggests that HS is decreasing BP variability in the HS group, while the association of HS with TBI did not show the same response. Baroreflex sensitivity was higher in both HS and HS+TBI compared to both Sham and TBI groups. TCA cycle and amino acids metabolites increased in all the groups with trauma compared to Sham, however the increase in the HS and TBI+HS was around 2.5X-fold, while for the TBI group it was around 1.5X-fold. Moreover, the lipids metabolites decreased for all the groups submitted to trauma, with the highest effects observed for the groups submitted to HS and TBI+HS. These results suggest that HS has a higher effect on metabolites abnormalities compared to TBI alone. Our results suggest that HS has a higher contribution for hemodynamics and metabolism abnormalities when compared to TBI alone. It is interesting that the association of TBI with HS does not seem to change parameters such HR and BP variability. However, further investigations are necessary to better understand the impact of the lack of alteration of these hemodynamics parameters, since this trauma combination is complex and the adequate treatment for these situations remains unclear. This study was supported by National Institutes of Health grants R01HL162120, R01HL159862 and the Department of Defense under grants W81XWH1810059. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.