Abstract 331: Argon Promotes Vasorelaxation in Rat Pulmonary and Mesenteric Arteries

Abstract

Introduction: Despite cardiopulmonary resuscitation (CPR), more than 90% of patients having an out-of-hospital cardiac arrest in the US still die or endure severe neurological damage due to ischemia/reperfusion (IR) injury. Ventilation with Argon during CPR improves oxygenation, cardiac output, and survival in a porcine model of cardiac arrest. Similarly, inhalation of the volatile anesthetic, Sevoflurane, during CPR improves hemodynamic outcomes, but its usefulness is limited by its anesthetic effect and potential harm to providers and bystanders. In contrast, non-anesthetic noble gases like Argon can be safely administered outside of the hospital and may serve as a feasible adjuvant to mitigate IR injury following cardiac arrest. We hypothesize that Argon can decrease pulmonary and/or systemic vascular resistance, which may improve hemodynamic outcomes. Methods: Pressure myography assays were performed on isolated rat pulmonary and mesenteric arteries to determine the ability of Argon to promote vasodilation. Vessels were mounted in microvessel perfusion chambers and challenged with oxygenated Krebs buffer balanced with Argon (65%Argon:30%O 2 :5%CO 2 ) or Nitrogen (65%N 2 :30%O 2 :5%CO 2 ). Changes in intra-luminal diameter were recorded. Statistics: one-way ANOVA, p< 0.05. Results: Pulmonary arteries dilated in response to O 2 , while mesenteric arteries constricted. Argon exposure made pulmonary vessels significantly more sensitive to O 2 -induced dilation (mean Argon dilation = 133%, mean N 2 dilation = 99%). Conversely, argon blunted the ability of O 2 to constrict mesenteric arteries (argon mean constriction = 35%, nitrogen mean constriction = 41%). Conclusion: Our results indicate that Argon has vasodilatory effects in both the pulmonary and systemic circulations, making it a potentially useful therapeutic tool for mitigating IR injury following cardiac arrest or other instances of prolonged hypoperfusion. Future studies will address the mechanism underlying the ability of an inert noble gas to affect vasoactive signaling pathways.