Systemic administration of allogeneic mesenchymal stem cells attenuates post-resuscitation left ventricular dysfunction in a porcine model of cardiac arrest.

BACKGROUND

Based on evidence that a systemic inflammatory response exacerbates multi-organ injury after resuscitation from cardiac arrest (CA), we tested the efficacy of allogeneic mesenchymal stem cell (MSC) administration early after return of spontaneous circulation (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 × 106; n = 10) 30-min post-ROSC. Intravenous EPI was given during the post-ROSC period as needed to maintain MAP ≥ 60 mmHg. Echocardiography, hemodynamic analysis, and serial blood sampling were performed for 4-hours post-ROSC, at which time the heart and brain were collected for post-mortem analysis of inflammation and injury.

RESULTS

Compared with saline-treated controls, MSC-treated animals exhibited improved post-ROSC LV function and lower cTnI levels, indicative of reduced myocardial injury. By design, both groups had a similar post-ROSC blood pressure and cardiac output, but the saline group required significantly more EPI. Allogeneic MSCs also decreased plasma reactive oxygen species and tended to attenuate the post-ROSC rise in circulating IL-6.

CONCLUSIONS

Early post-ROSC delivery of allogeneic MSCs attenuates LV dysfunction and reduces the need for pharmacologic hemodynamic support after CA in swine, suggesting that systemic MSC administration may be an effective strategy to improve patient outcomes after resuscitation from CA.