Abstract 9769: Bicarbonate Treatment Before Reperfusion Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibition of Spleen-Mediated Inflammatory Response

Introduction: The spleen plays an important role in mediating myocardial ischemia/reperfusion injury (IRI). Sodium bicarbonate (NaHCO 3 ) administration is reported to inhibit spleen-mediated inflammatory responses via vagus nerve activation. Hypothesis: NaHCO 3 treatment attenuates myocardial IRI in a spleen dependent-manner. Methods: C57BL/6 mice underwent 40 minutes of LCA occlusion followed by 60 minutes of reperfusion. PBS (control), NaHCO 3 (1 mEq/ml), or 5.8% NaCl of equivalent osmolality were administered intravenously (IV) 10 minutes before reperfusion at a dose of 1 μl/g. Intraperitoneal (IP) NaHCO 3 was administered 10 minutes before reperfusion at low dose (0.25 mEq/ml, 20 μl/g), high dose (0.5 mEq/ml, 20 μl/g), or as a localized topical rinse of the spleen or liver (1 mEq/ml, 1μl/g). Infarct size (IF), denoted as percentage of risk region (RR, % of LV), was measured by TTC-Phthalo blue staining. Additional groups (n=4) without IRI received IV PBS, IV NaHCO 3 , or IP NaHCO 3 splenic rinse and underwent plasma and spleen harvest 10 minutes after treatment. Results: RR was comparable among all groups with IRI. Among IV-treated groups (Figure A), IF was similar with PBS and 5.8% NaCl (51±4% and 46±3%), while IV NaHCO 3 significantly reduced IF to 25±3% (p<0.05 vs. PBS & 5.8% NaCl). Among IP-treated groups (Figure B), low-dose NaCO3, high-dose NaHCO 3 , and topical NaHCO 3 spleen rinse equally attenuated IF compared to control (p<0.05), while topical NaHCO 3 liver rinse did not reduce IF (51±2%, p = NS vs. control). IV NaHCO 3 administration elevated base excess and HCO 3 - without changing pH, pO 2 or pCO 2 . IV and topical splenic NaHCO 3 elevated plasma GLP-1 and enhanced splenic monocyte M2 polarization. Conclusions: Both IV and IP NaHCO 3 treatment attenuated IF via inhibiting spleen-mediated inflammatory responses. Sodium bicarbonate administered prior to reperfusion may a potential therapeutic adjunct for ischemia/reperfusion injury in acute coronary syndrome.