Abstract Sun203: Peripheral Vasodilation by the Noble Gas Argon Is Mediated by Endothelial Nitric Oxide in Rat Mesenteric Arteries

Abstract

Introduction: Increasing evidence shows that noble gas postconditioning by inhaled Xenon or Argon (Ar) after return of spontaneous circulation (ROSC) improves survival with favorable neurological function. When given during cardiopulmonary resuscitation (CPR), though, i.e. before ROSC, Ar increases cardiac output during chest compressions in a pig and a rat model of cardiac arrest. We believe it does so by decreasing pulmonary resistance as shown in isolated lungs and by decreasing systemic vascular resistance, subject of the present IACUC-approved study on isolated arteries. Methods: In a first set of experiments, we used pressurized (20 mmHg, no flow) 4 th generation mesenteric arteries isolated freshly from euthanized adult Sprague Dawley rats to measure diameter changes by confocal microscopy. Vessels were super-fused by oxygenated Krebs buffer balanced with 87.5% Ar; 7.5% O 2 ; 5% CO 2 or 87.5% N 2 ; 7.5% O 2 ; 5% CO 2 in a micro-vessel perfusion chamber. To test whether Ar promotes vasodilation through endothelial nitric oxide (NO), we then repeated these experiments in the presence of either the NO synthase inhibitor L-NG-Nitroarginine methyl ester (LN, 0.5 mM) or sodium deoxycholate (SDC, 0.2 mM), a detergent to inactivate endothelial cells and eliminate endothelium-dependent relaxation. All vessels were pre-constricted with 1 µM norepinephrine throughout the experiment and vasoconstricted by 25 mM KCl or vasodilated by 1 µM of the endothelium-independent vasodilator sodium nitroprusside (SNP) at the end. Diameters were normalized to baseline %, data are mean ± SEM. Statistics: ANOVA for repeated measures, p<.05 * vs control. Results: Argon increased the diameter by +6.7±1.4%* (n=15) from baseline; KCl decreased it by -5.5±2.3%* (Fig 1). LN (n=6) vs SDC (n=7) alone had no significant effects on diameter: -1.9±1.4% vs -0.4±0.8%, respectively, but abolished dilation by Argon completely: -3.1±1.7% vs -0.6±0.9%, respectively. All vessels still significantly dilated with SNP afterwards: +4.7±1.1%* vs +6.2±1.2%*, respectively. Conclusion: Argon’s mild but significant vasodilatory effect on peripheral vasculature appears mediated by endothelial NO release. Along with increased cardiac output by improved right-to-left heart flow due to pulmonary vasodilation, it may aid to improved peripheral perfusion during and after cardiac arrest. Future studies will address underlying signaling pathways and clinical applicability in more detail.