# Inhaled Argon during Cardiopulmonary Resuscitation -A Novel Therapy to Improve Vital Organ Function and Survival after Cardiac Arrest > **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · — ## Abstract As a board-certified VA anesthesiologist and cardiovascular physiologist, I study protective mechanisms against ischemia/reperfusion (IR) injury of vital organs ultimately geared to help our often multi-morbid Veteran patients who are at an increased risk for myocardial infarction and, thus, cardiac arrest (CA). In fact, more than 380,000 patients in the US alone suffer an out-of-hospital CA each year, a leading cause of often debilitating illness and death worldwide. Timely reperfusion by cardiopulmonary resuscitation (CPR) is of utmost importance; yet, reperfusion itself paradoxically adds to IR injury, lethal arrhythmias and cell death, and even with the best mechanical CPR, >90% still have severe neurological deficits or die. Thus, organ-protective strategies early during resuscitation are desperately warranted. The beneficial effect of ventilating with the non- anesthetic noble gas Argon (Ar) after successful resuscitation, i.e. return of spontaneous circulation (ROSC), has been tested in only very few CA studies, none of which, though, has utilized Ar to its full potential of organ protection when given immediately upon reperfusion, i.e. the very beginning of CPR, to increase the rate of ROSC, nor have they explored specific mechanisms of action. Despite lack of chemical reactivity due to completely filled outer electron orbitals, noble gases can exert discernible biological effects by interacting with signaling proteins, ion channels, and/or receptors. Supported by strong preliminary ex and in vivo data, we hypothesize that Ar improves survival and neurologically favorable outcome after prolonged CA and extended CPR by i) decreasing arrhythmias and ii) increasing vital organ perfusion primarily due to pulmonary vasorelaxation with increased right-to-left blood flow and, thus, increased systemic cardiac output and blood flow to vital organs during and after CPR. Hence, our revised multi-pronged study has three specific aims: AIM 1: Define the mechanism by which Ar exerts its anti-arrhythmic effect. In vitro electrophysiological patch-clamping experiments complement ex vivo optical mapping in rat isolated hearts in the absence/ presence of Ar with or without IR. Experiments in Aim 3 will confirm and quantify the benefit of this effect in vivo. This provides the first systematic characterization of Ar’s anti-arrhythmic properties. AIM 2: Define the mechanism by which Ar regulates pulmonary and peripheral vascular tone. Experi- ments in rat isolated systemic and pulmonary vessels will be scaled up and tested in ex vivo models of isolated intact hearts and lungs with or without IR and in the absence or presence of Ar and/or putative pathway agonists or antagonists. Experiments in Aim 3 will confirm and quantify the benefits of these effects in vivo. This will lead to previously undescribed mechanisms of vascular tone regulations by Ar. AIM 3: Evaluate the therapeutic potential of early Ar inhalation to improve ROSC, cardiac and cerebral recover... ## Key facts - **NIH application ID:** 10589390 - **Project number:** 1I01BX005993-01A1 - **Recipient organization:** VETERANS HEALTH ADMINISTRATION - **Principal Investigator:** Matthias L. Riess - **Activity code:** I01 (R01, R21, SBIR, etc.) - **Funding institute:** VA - **Fiscal year:** 2024 - **Award amount:** — - **Award type:** 1 - **Project period:** 2023-10-01 → 2027-09-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10589390 ## Citation > US National Institutes of Health, RePORTER application 10589390, Inhaled Argon during Cardiopulmonary Resuscitation -A Novel Therapy to Improve Vital Organ Function and Survival after Cardiac Arrest (1I01BX005993-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10589390. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*