Abstract 359: Systemic Administration of Allogeneic Mesenchymal Stem Cells Attenuates Post-Resuscitation Left Ventricular Dysfunction in a Porcine Model of Cardiac Arrest

Abstract

Introduction: Advances in CPR have increased the likelihood of achieving ROSC after cardiac arrest (CA), but >50% of initially resuscitated patients die before hospital discharge. Evidence that a systemic inflammatory response exacerbates post-ROSC injury supports investigation of anti-inflammatory therapies in this setting. Accordingly, we tested the efficacy of allogeneic mesenchymal stem cell (MSC) administration early after ROSC in a porcine model of CA. Methods: Swine (n=33) were subjected to 10 min CA followed by mechanical CPR with defibrillation and intravenous epinephrine (EPI; 0.015 mg/kg). Animals that achieved ROSC (n=19) were blindly randomized to intraventricular saline (n=9) or allogeneic bone marrow-derived MSCs (55±2 x 10 6 ; n=10) 30 min post-ROSC. Intravenous EPI was given during the post-ROSC period as needed to maintain MAP ≥60 mmHg. Left ventricular (LV) function and plasma cardiac troponin I (cTnI) were assessed for 4 hr post-ROSC, at which time heart tissue was collected to assess myocardial inflammation (RT-PCR). Results: Compared with saline-treated controls, MSC-treated animals exhibited improved post-ROSC LV wall thickening ( A ) and lower cTnI levels, indicative of reduced myocardial injury. By design, both groups had a similar post-ROSC MAP and cardiac output, but the saline group required significantly more EPI ( B ). Although a similar degree of monocyte infiltration (CCR2) and macrophage expansion (CD68) was observed in both groups, MSCs increased expression of the anti-inflammatory marker Arginase1 ( C ) and tended to attenuate the post-ROSC rise in circulating IL-6 ( D ). Conclusion: Early post-ROSC delivery of allogeneic MSCs attenuates LV dysfunction and reduces the need for pharmacologic hemodynamic support after CA in swine. These results indicate that systemic MSC administration may be an effective immunomodulatory strategy to reduce post-resuscitation injury, particularly if protective effects extend to the brain.