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Administration of glucosamine (GlcN) following trauma-hemorrhage (TH) increased tissue levels of O-linked N-acetylglucosamine (GlcNAc) attenuated circulating proinflammatory cytokines TNF-ct and 1L-6, and improved cardiac function. However, the mechanism(s) by which increased O-GlcNAc levels improve recovery and decrease the inflammatory response is unclear. Therefore, the goal of this study was to determine if the beneficial effect of GlcN was mediated by downregulation of NF-KB signaling pathway following TH. Fasted male rats were subject to TH by bleeding to a mean arterial blood pressure of 40 mmHg for 90 minutes followed by 60 minutes resuscitation; GleN (2.5mls, 150mM) or vehicle (2.5mls normal saline) were administered mid-way through resuscitation. Two hours later mean arterial pressure, heart rate and ±dp/dt were recorded and tissues harvested. Consistent with our earlier study GlcN improved cardiac function at the end of resuscitation. In hearts from vehicle treated rats, there were increased levels of intercellular adhesion molecule 1 protein ICAM 1), IκB-α phosphorylation, nuclear NF-KB protein and increased NF-κB nuclear DNA binding activity compared to sham controls. GlcN treatment significantly decreased ICAMI expression, IκB-α phosphorylation, nuclear NF-κB expression and NF-KB DNA binding activity. Thus, GleN administration during resuscitation attenuated NFKB signaling pathway in the heart and this may contribute to the protection associated with increased protein O-GlcNAc levels. [ABSTRACT FROM AUTHOR]

Although 17β-estradiol (E2) administration after trauma-hemorrhage (T-H) produces salutary effects on cardiac function, the precise mechanism remains unknown. Additional studies have shown that cardiomyocyte Ica-L increased after T-H and the protective effect of E2 on cardiac function correlated with the attenuation of cardiomyocyte Ica-L. Although E2 produces various salutary effects, it is not known whether ER-α agonist (PPT) or β agonist (DPN) also attenuates cardiomyocyte Ica-L. Male rats (250-275 g) underwent T-H (removal of 60% of the circulating blood and fluid resuscitation after 90 min of hypotension) and received PPT, DPN (10 µg/kg, IV) or Cyclodextrin (20.7 mg/kg, IV, control) during resuscitation. Left ventricular (LV) performance was measured at 24 h and cardiomyocytes were then isolated. The whole-cell patch-clamp technique was employed to measure cardiomyocyte Ica-L. The results indicated that LV performance was decreased and cardiomyocyte Ica-L increased significantly after T-H; however, DPN restored cardiac function and attenuated the increase of cardiomyocyte Ica-L. In contrast, the beneficial effects of PPT on cardiac function did not reach a significance level. Thus, the salutary effect of E2 following trauma-hemorrhage appears to be primarily mediated via the ER-β receptor and may be a consequence of attenuation of cardiomyocyte Ica-L [ABSTRACT FROM AUTHOR]