ns-309 and Heart-Arrest

Cardiovascular dysfunction after cardiac arrest is a common finding. It is unknown whether altered endothelium-mediated vasoreactivity contributes to this dysfunction. We hypothesised that cardiac arrest and resuscitation results in impaired endothelial function. This was addressed by measurements of inflammatory and endothelial plasma markers and of endothelium-dependent vasodilatation in coronary and mesenteric arteries in rats after cardiac arrest and resuscitation.. Male Sprague Dawley rats underwent either asphyxia-induced cardiac arrest for 5 min and subsequent resuscitation (n = 30) or a sham procedure (control animals, n = 39). Animals were euthanised after 30 min or 2 h. Blood was analysed for TNF-α, IL-1β, IL-6, IL-10, sE-selectin, sP-selectin, sVCAM-1, ICAM-1, VEGF-α and vWF. Arterial rings of the left anterior descending coronary artery and mesenteric resistance arteries were mounted in microvascular myographs, and concentration-response curves were constructed.. The plasma levels of the endothelial markers, sP-selectin and vWF increased following cardiac arrest at both 30 min and 2 h. Acetylcholine-induced endothelium-dependent and mainly nitric oxide (NO)-mediated vasodilatation was impaired in the coronary arteries at 30 min, but not 2 h after resuscitation. Endothelium-derived hyperpolarisation (EDH)-type vasodilatation induced by NS309 and vasodilatation induced by the NO donor sodium nitroprusside was unaltered. In parallel with systemic hypotension, mesenteric arteries exhibited a larger response to NS309 2 h after resuscitation.. The present results show marked endothelial alterations after cardiac arrest and resuscitation reflected by increased endothelial plasma markers, impaired NO-mediated coronary vasodilatation in the early post-resuscitation phase and enhanced EDH-type vasodilatation in mesenteric arteries later in the post-resuscitation phase.

Topics: Acetylcholine; Animals; Asphyxia; Coronary Vessels; Dose-Response Relationship, Drug; Heart Arrest; Indoles; Male; Mesenteric Arteries; Microcirculation; Myography; Nitric Oxide; Nitric Oxide Donors; Oximes; Rats; Rats, Sprague-Dawley; Vascular Resistance; Vasodilation; Vasodilator Agents