Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

Abstract

Resveratrol has been shown to potentiate mitochondrial function and extend longevity; however, there is no evidence to support whether resveratrol can improve survival or prolong life following hemorrhagic shock. We sought to determine whether (a) resveratrol can improve survival following hemorrhage and resuscitation and (b) prolong life in the absence of resuscitation. Using a hemorrhagic injury (HI) model in the rat, we describe for the first time that the naturally occurring small molecule, resveratrol, may be an effective adjunct to resuscitation fluid. In a series of three sets of experiments we show that resveratrol administration during resuscitation improves survival following HI (p < 0.05), resveratrol and its synthetic mimic SRT1720 can significantly prolong life in the absence of resuscitation fluid (<30 min versus up to 4 h; p < 0.05), and resveratrol as well as SRT1720 restores left ventricular function following HI. We also found significant changes in the expression level of mitochondria-related transcription factors Ppar-α and Tfam, as well as Pgc-1α in the left ventricular tissues of rats subjected to HI and treated with resveratrol. The results indicate that resveratrol is a strong candidate adjunct to resuscitation following severe hemorrhage.

Alteration of cytokine profile following hemorrhagic shock

“…Sperry et al have shown that increase in IL-6 levels in HI correlates with multiple organ failure (MOF); male gender with higher IL-6 serum levels being more prone to MOF [14]. In our study in male SD rats, IL-6 level in plasma remained high at 2h and 3h post-resuscitation and was reduced with RSV administration consistent with the better outcome after injury [11]. This is consistent with a previous study that showed increased hepatic myeloperoxidase activity, cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, ICAM-1, and IL-6 levels [6].…”

“…HI leads to declined organ function and mortality which are significantly improved by resuscitation in the presence of small molecule activators of SIRT1, resveratrol and SRT1720 [5, 11]. In order to understand the events leading to declined cardiac function, we tested the gene expression level of NF-κb, a transcription factor that promotes the expression of inflammatory genes and a panel of NF-κb-regulated cytokines in the heart following HI and resuscitation, by real time PCR (Figure 1).…”

“…HI procedure and hemodynamics were described before [11]. Briefly, HI was induced by bleeding 60% of the circulating blood volume in 45 minutes and maintaining the animals at low blood pressure (40+5 mm Hg) for another 45 minutes followed by resuscitation as described below.…”

“…Our continued studies demonstrated that resveratrol can improve survival and prolong life following HI even in the absence of resuscitation fluid [11]. However the role of resveratrol on the inflammatory response following HI or the role of NF-κb regulated genes is not well defined.…”

Mitochondrial function in hypoxic ischemic injury and influence of aging

“…Further studies are necessary to determine whether additional targets exists for resveratrol and the contribution of SIRT1 activation in in vivo studies using resveratrol. A recent study published from our laboratory demonstrates that salutary effect of resveratrol in prolonging life after severe hemorrhage could be at least partially mimicked by the STAC SRT1720 (Ayub et al , 2015). …”