627.7 - Exacerbated Vascular Inflammation Following Traumatic Hemorrhage in Obese Rats

Belinda McCully (Western University of Health Sci, Oregon Health amp; Science University), Jazmin Cole (University of Oregon), Sahana Kumaran (University of Oregon), Jonathan Kato (University of Oregon), Xinhao Zhuang (University of Oregon), Julia Wolf (University of Oregon), Grant Henson (University of Oregon), Ashley Walker (University of Oregon)

Introduction: Obesity increases the risk for morbidity and mortality in trauma patients. These complications are associated with prolonged tissue hypoperfusion, hypercoagulability, and edema that reflect profound vascular damage. Traumatic hemorrhage acutely attenuates vascular responsiveness, but the degree of this dysfunction during the obese state is not known. Traumatic hemorrhage also increases circulating inflammatory cytokines; however, the local inflammatory response in vascular cells is unknown. We hypothesized that obesity potentiates trauma-induced vascular inflammation and dysfunction.

Methods: Male Sprague-Dawley rats (~250g) fed either normal chow (NC; 13.5% kcal fat, n=20), moderate-fat (MF; 33% kcal fat, n=20), or high-fat (HF; 60% kcal fat, n=20) diet for 6-8 weeks were assigned to a traumatic hemorrhage protocol or sham control. Under anesthesia, hemorrhage was induced by the laceration of a mesenteric artery and a Grade V splenic injury. Hypotension (mean arterial pressure = 30–40 mm Hg) was maintained for 30 minutes. Vasoconstrictor and vasodilator properties were assessed ex vivo in isolated mesenteric arteries pre- and post- hemorrhage. Carotid arteries collected after hemorrhage or sham control were flushed with trizol to collect endothelial cells (ECs). Gene expression was assessed in ECs and the remaining carotid artery (media + adventitia) cells for pro-inflammatory interleukin (IL)-1β, and IL-6, pro-oxidant NADPH oxidase 2 (NOX2), and α-adrenergic receptor.

Results: In NC rats, hemorrhage attenuated norepinephrine-induced vasoconstriction and endothelium-dependent dilation. This was accompanied by elevated IL-1β expression in carotid artery ECs and elevated IL-1β, IL-6, NOX2, and α-adrenergic receptor expression in the carotid artery media + adventitia post-hemorrhage versus sham control. In MF and HF rats, norepinephrine-induced vasoconstriction and endothelium-dependent dilation did not change pre- to post-hemorrhage. In sham animals, endothelial cell IL-1β and NOX2 expression were higher in HF compared with NC rats. Similar to NC rats, the MF and HF rats had higher IL-1β expression in carotid artery ECs, and IL-1β, IL-6, NOX2, and α-adrenergic receptor expression in the carotid artery media + adventitia post-hemorrhage compared with sham. The hemorrhage-induced elevation of IL-1β in carotid artery ECs and media + adventitia was greater in HF rats compared with NC and MF rats.

Conclusion: Our clinically-relevant model of traumatic hemorrhage attenuates vascular responsiveness and induces vascular inflammation. The attenuated vascular responsiveness following hemorrhage is absent in MF and HF rats, while the elevated vascular inflammation persists. HF rats have an amplified arterial inflammatory response to hemorrhage, both in ECs and in cells of the media + adventitia. The augmented vascular inflammatory response to hemorrhage in HF rats may explain the worse outcomes in obese trauma patients.

Support or Funding Information

Funding: University of Oregon - OHSU Collaborative Seed Fund