Abstract 290: Endothelial Dysfunction in a Rat Model of Asphyxia-Induced Cardiac Arrest
Background: Altered vasoreactivity and elevated markers of endothelial activation are found following cardiac arrest (CA) and resuscitation. However, it is unknown whether the described altered vasoreactivity reflects influence from humoral factors, affection of the underlying smooth muscle or a change in the endothelium itself. Furthermore, it is unknown how the inflammatory markers correlate to endothelial function.
The aim of the present study was to assess endothelial function and the relation to plasma markers of inflammation and adhesion, CA and resuscitation.
Methods: Male Sprague Dawley rats underwent 5 min. of asphyxia-induced CA and subsequent resuscitation. After return of spontaneous circulation (ROSC) animals were euthanized after 30 min. or 2 hrs. Sham operated animals were used as controls. At the end of the experiment blood was drawn and analyzed for IL-1β, IL-6, IL-10, TNF-α, ICAM-1, VCAM-1, VEGF-α, vWF and sP-Selectin. Segments of the Left coronary artery (LCA) and mesenteric resistance arteries were mounted in microvascular myographs. Concentration-response curves for acetylcholine (ACH), NS309, and sodium nitroprusside where obtained.
Results: LCA-segments exhibited an impaired vasodilation to ACH after 30 min. of ROSC as CA animals dilated to a max of 66 ± 2 vs. 94 ± 8% in the sham group (Mean ± SE; P=0.0014). After 2 hrs. of ROSC vasoreactivity was comparable to sham groups for all drugs tested. The mesenteric arteries exhibited a larger response to NS309 after 2 hrs. of ROSC compared to 2 hr. sham (logEC50 ± SE: 0.43 ± 0.05 vs. 1.85 ± 0.23 µM; P<0,001). Levels of sP-selectin, vWF and sVCAM-1 were elevated in both CA groups vs. sham groups, with no correlation to vasoreactivity.
Conclusion: Endothelium-dependent ACH-induced nitric oxide (NO)-mediated vasodilation was blunted in LCA segments in the early post-resuscitation phase, NS309-induced endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation was enhanced in mesenteric resistance arteries in the intermediate post-resuscitation phase. There was no relation of vasoreactivity to plasma markers of adhesion and inflammation. The altered vascular reactivity may explain impaired coronary flow and hypotension in the restitution phase after cardiac arrest.
- © 2012 by American Heart Association, Inc.