stilbenes and Heart-Arrest

To investigate the protective effects and its potential mechanism of resveratrol preconditioning on rat cardiac arrest after return of spontaneous circulation (ROSC) with the study of hemodynamic parameters and nitrative stress in myocardium.. Cardiac arrest SPF SD rat model was established by transoesophageal cardiac alternating current stimulation. Intervention was implemented 15 min before cardiac arrest. Twenty four rats with ROSC after cardiac arrest were randomly assigned into five groups: vehicle, sham, resveratrol 2.3 mg/kg (A group), resveratrol 0.23 mg/kg (B group) and resveratrol 0.023 mg/kg (C group). Heart rate, mean arterial pressure, and left ventricular variables (+ dp/dtmax and - dp/dtmin) were recorded in 0.5 h, 1.0 h, 2.0 h, 3.0 h, and 4.0 h respectively. Rats were sacrificed at 4 h after ROSC, and hearts were removed for determining expression of inducible nitric oxide synthase (iNOS) protein, myocardial peroxynitrite, and nitrotyrosine.. Global ROSC rate was 72.7% after the induction of cardiac arrest. Resveratrol preconditioning did not improve ROSC rate significantly. Heart rate and blood pressure declined at early phase of ROSC, then heart rate recovered to the baseline value, but blood pressure still declined progressively. There were no significant differences between resveratrol groups and vehicle group. Myocardial function worsened progressively even after ROSC. Resveratrol improved cardiac function significantly, especially in lower concentration groups. Myocardial iNOS expression, peroxynitrite, and nitrotyrosine content increased significantly after ROSC. Resveratrol decreased these products significantly, and lower concentration groups did better.. Resveratrol preconditioning could improve cardiac dysfunction after ROSC, which may be associated with its inhibitory effect on nitrative stress.

Topics: Animals; Disease Models, Animal; Heart; Heart Arrest; Ischemic Preconditioning; Nitric Oxide Synthase Type II; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Tyrosine

Resveratrol is a natural polyphenol found in grapes and wine and has been associated with protective effects against cardiovascular diseases. In vitro, both resveratrol preconditioning (RPC) and ischemic preconditioning (IPC) require activation of sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, to induce neuroprotection against cerebral ischemia. In the present study, we tested two hypotheses: (a) that neuroprotection against cerebral ischemia can be induced by RPC in vivo; and (b) that RPC neuroprotection involves alterations in mitochondrial function via the SIRT1 target mitochondrial uncoupling protein 2 (UCP2). IPC was induced by 2 min of global ischemia (temporary bilateral carotid artery occlusion with hypotension), and RPC, by i.p. injection of resveratrol at 10, 50 and 100 mg/kg dosages. Forty-eight hours later, we compared the neuroprotective efficacy of RPC and IPC in vulnerable cornu ammonis 1 hippocampal pyramidal neurons using a rat model of asphyxial cardiac arrest (ACA). SIRT1 activity was measured using a SIRT1-specific fluorescent enzyme activity assay. In hippocampal mitochondria isolated 48 h after IPC or RPC, we measured UCP2 levels, membrane potential, respiration, and the mitochondrial ATP synthesis efficiency (ADP/O ratio). Both IPC and RPC induced tolerance against brain injury induced by cardiac arrest in this in vivo model. IPC increased SIRT1 activity at 48 h, while RPC increased SIRT1 activity at 1 h but not 48 h after treatment in hippocampus. Resveratrol significantly decreased UCP2 levels by 35% compared to sham-treated rats. The SIRT1-specific inhibitor sirtinol abolished the neuroprotection afforded by RPC and the decrease in UCP2 levels. Finally, RPC significantly increased the ADP/O ratio in hippocampal mitochondria reflecting enhanced ATP synthesis efficiency. In conclusion, in vivo resveratrol pretreatment confers neuroprotection similar to IPC via the SIRT1-UCP2 pathway.

Topics: Adenosine Triphosphate; Animals; Asphyxia; Benzamides; Brain Ischemia; Carotid Artery Diseases; Disease Models, Animal; Heart Arrest; Hippocampus; Hypotension; Ion Channels; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Proteins; Naphthols; Neuroprotective Agents; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Respiration; Resveratrol; Signal Transduction; Sirtuin 1; Sirtuins; Stilbenes; Uncoupling Protein 2