Improved Cardiovascular Tolerance to Hemorrhage after Oral Resveratrol Pretreatment in Dogs

Abstract

Resveratrol has been shown to preserve organ function and improve survival in hemorrhagic shock rat models. This study investigated whether seven days of oral resveratrol could improve hemodynamic response to hemorrhage and confer benefits on risk of acute kidney injury (AKI) without inducing coagulopathy in a canine model. Twelve greyhound dogs were randomly allocated to receive oral resveratrol (1000 mg/day) or placebo for seven days prior to inducing hemorrhage until a targeted mean blood pressure of ≤40 mmHg was achieved. AKI biomarkers and coagulation parameters were measured before, immediately following, and two hours after hemorrhage. Dogs were euthanized, and renal tissues were examined at the end of the experiment. All investigators were blinded to the treatment allocation. A linear mixed model was used to assess effect of resveratrol on AKI biomarkers and coagulation parameters while adjusting for volume of blood loss. A significant larger volume of blood loss was required to achieve the hypotension target in the resveratrol group compared to placebo group (median 64 vs. 55 mL/kg respectively, p = 0.041). Although histological evidence of AKI was evident in all dogs, the renal tubular injury scores were not significantly different between the two groups, neither were the AKI biomarkers. Baseline (pre-hemorrhage) maximum clot firmness on the Rotational Thromboelastometry (ROTEM®) was stronger in the resveratrol group than the placebo group (median 54 vs. 43 mm respectively, p = 0.009). In summary, seven days of oral resveratrol did not appear to induce increased bleeding risk and could improve greyhound dogs’ blood pressure tolerance to severe hemorrhage. Renal protective effect of resveratrol was, however, not observed.

The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury

“…Light microscopy features may include dilation of PT lumens, flattening of epithelium, vacuolization, simplification, and loss of brush border (which provides the large surface area needed for reabsorption of nutrients and electrolytes normally) (Fig. 1) [13]. Similarly, PT electronic microscopy demonstrates the loss of brush border cells in association with subtle but notable changes, including mitochondrial swelling and fragmentation (Fig.…”

“…Bar is 2 μm. This figure is reproduced with permission from the publisher of reference [13]. EM, electron micrograph.…”

Editorial: Special Issue “Addressing New Therapeutic Strategies Using Models”

“…Davis et al [ 8 ] demonstrated that resveratrol treatment did not appear to induce an increased bleeding risk and could improve greyhound dogs’ blood pressure tolerance to severe hemorrhage. Despite this, they did not observe the kidney-protective effects of resveratrol.…”