The Role of Beta‐2 Adrenergic Receptors in Cardiac Bioenergetics Following Severe Burns

Abstract

Severe burn injury is characterized by increased energy expenditure, and altered mitochondrial function is thought to be central to the hypermetabolic response to burns. As catecholamines are an important driver of the hypermetabolic stress response to burn, we set out to determine the role of adrenergic signaling through Beta‐2 adrenergic receptors in cardiac mitochondrial function following burn. We hypothesized that a loss of adrenergic signaling would attenuate cardiac mitochondrial dysfunction in response to burns.We used beta ‐2 adrenergic receptor knockout mice (ADRB2‐KO) and wild type controls (WT). Mice received a 30% of total body surface area scald burn or a sham burn and were sacrificed one week following injury. Hearts were excised and mitochondrial function was measured in saponin‐permeabilized myofiber bundles by high‐resolution respirometry. Data were analyzed using two‐way ANOVA and Bonferroni post‐test to compare all groups.Mitochondrial respiratory capacity was significantly reduced in both WT (P<0.01) and KO (P<0.01) mice following burn, although there was no difference between WT and KO mice. In WT animals, respiration coupled to ATP production was significantly lower in the burn animals compared to shams (p< 0.05). In contrast, respiration coupled to ATP production was not different in sham and burn treated ADRB2‐KO mice. Mitochondrial flux control ratios (leak and couple respiration normalized to maximal uncoupled respiration) were significantly higher in burned WT mice compared to sham (P<0.05). However, mitochondrial flux control was not significantly altered by burn in KO mice.Collectively, these data underscore the role of catecholamines and adrenergic stress in the metabolic response to burns. Specifically, ablation of beta 2 adrenergic signaling in the heart prevents cardiac mitochondrial dysfunction in response to severe burn trauma.Support or Funding InformationThis study was supported by grants from the National Institute of Health (P50‐GM60338, R01‐GM56687, and GM 112936‐01), Shriners Hospitals for Children (80100, 87300, 71008, 70900, 85116, 71000), and SSF grant for Craig Porter. This study was also conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advanc‐ing Translational Sciences, National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.