Attenuation of Multiple Organ Damage by Continuous Low-Dose Solvent-Free Infusions of Resveratrol after Severe Hemorrhagic Shock in Rats.

Tobias Müller,Frank Petrat,Michael Kirsch

doi:10.3390/nu9080889

Abstract

Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25–30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer’s. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats.

Highlights

Traumatic hemorrhage, i.e., the rapid and hemodynamically significant loss of intravascular volume, creates great morbidity in the injured [1,2] and leads to the most frequent cause of preventable deaths after severe traumatic injury [3,4,5,6,7]
Our results indicate that very low doses of resveratrol, continuously infused during after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic multiple organ damage in an exacerbated rat model that is close to the clinical situation
Our results indicate that even low doses of the polyphenol (0.06 or 0.18 mg/kg), continuously infused intravenously, diminish liver and intestinal injury by attenuating neutrophil invasion and tissue hemorrhage, as indicated by the decreased tissue MPO activity and tissue Hb concentrations, macroscopic score of the intestine (Figure 3) as well as markers of hepatic injury (Figure 4)

Summary

Introduction

I.e., the rapid and hemodynamically significant loss of intravascular volume, creates great morbidity in the injured [1,2] and leads to the most frequent cause of preventable deaths after severe traumatic injury [3,4,5,6,7]. A model was used that is close to the current practice for treatment after severe trauma and blood loss in humans according to the Trauma Register of the Deutsche Gesellschaft für Unfallchirurgie [9,10,11]. Based on this model, we studied the therapeutic effects of resveratrol (trans-3,40 ,5-trihydroxystilbene), a naturally occurring plant antibiotic (phytoalexine).

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Results

Discussion

Conclusion