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. 2015 Apr 13;21(1):305-12.
doi: 10.2119/molmed.2015.00013.

Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

Ahmar Ayub  1 , Ninu Poulose  1 , Raghavan Raju  1   2   3
Affiliations

Resveratrol Improves Survival and Prolongs Life Following Hemorrhagic Shock

Ahmar Ayub et al. Mol Med. .

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.

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Figures

Figure 1
Figure 1
Resveratrol (RSV) improves survival after HI. (A) Kaplan-Meier survival curves for HI + Veh (n = 12) and HI + RSV (n = 8) groups. p < 0.05. (B) Weight gain/loss for HI + Veh (n = 5) and HI + RSV (n = 7), Mean ± SE; * indicates p < 0.05 compared with weight in the Veh treated group on the respective day. (C) dP/dt 10 d following HI; (n = 4–6); Bars represent mean ± SE. *indicates p < 0.05 compared with the Veh control.
Figure 2
Figure 2
Resveratrol (RSV) and SRT1720 prolongs life after HI without resuscitation. (A) Kaplan-Meier survival curves for HI + Veh, HI + RSV and HI + SRT1720 (n = 5–6). *p < 0.05 versus HI + Veh, both curves. (B) Mean arterial pressure (MAP) at maximum bleed out (MBO), treatment (TX) with Veh, RSV or SRT1720, 5 min after TX, 10 min after TX and 15 min after TX in HI + Veh, HI + RSV and HI + SRT1720 (n = 5–6). Bars represent mean ± SE. *p < 0.05 versus HI + Veh. (C) MAP from the onset of hemorrhage to immediately prior to euthanasia in individual animals in HI + Veh, HI + RSV and HI + SRT1720 groups. (n = 5–6). Black lines: HI + Veh; blue lines: HI + SRT1720; red lines: HI + RSV.
Figure 3
Figure 3
Hemodynamics at 2 h after resuscitation: mean arterial pressure (MAP) (A) and heart rate (HR) (B) at the start of resuscitation and at 2 h after resuscitation in HI + Veh, HI + resveratrol (RSV) and HI + SRT1720; n = 5–6; bars represent mean ± SE; * indicates p < 0.05 compared with the respective value at resuscitation. (C) ±dP/dt in sham group and at 2 h after resuscitation in HI + Veh, HI + RSV and HI + SRT1720 groups; (n = 4–5); bars represent mean ± SE. p < 0.05 compared with sham (*) or HI + Veh (#). (D) Lactate levels before HI and at 2 h after resuscitation in HI + Veh, HI + RSV and HI + SRT1720; n = 5–6; bars represent mean ± SE; p < 0.05 versus HI + Veh; * indicates p < 0.05 compared with preresuscitation.
Figure 4
Figure 4
Effect of resveratrol (RSV) and SRT1720 on Tfam, Ppar-α and Pgc-1α expression following HI. HI down regulated the mRNA expression of Ppar-α (A) mitochondrial transcription factor Tfam (B) and Pgc-1α (C) in the heart and the levels restored by RSV treatment. The values are normalized to sham; n = 4–6. Bars represent mean ± SE. p < 0.05 compared with sham (*) or HI + Veh (#).
Figure 5
Figure 5
Effect of resveratrol (RSV) and SRT1720 (SRT) on Tfam, Ppar-α and Pgc-1α protein level following HI. HI significantly downregulated Ppar-α (A,D) and Pgc-1 expressions (C,F) and the levels were restored significantly with RSV. RSV and SRT augmented Tfam expression levels (B,E). Western blots from three experiments were used in the semiquantitation. Bars represent mean + SE. n = 4–6. p < 0.05 compared with sham (*) or HI + Veh (#).
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