UAMC-3203 or/and Deferoxamine Improve Post-Resuscitation Myocardial Dysfunction Through Suppressing Ferroptosis in a Rat Model of Cardiac Arrest
Blocking ferroptosis has been shown to reduce ischemia-reperfusion injury in certain pathological conditions. However, its role in post-resuscitation myocardial dysfunction (PRMD) remains unclear. Here, we assessed the therapeutic efficacy of ferroptosis inhibitors (UAMC-3203 and/or Deferoxamine) on PRMD using a rat model of cardiac arrest. We also examined changes in key ferroptosis markers in the myocardium. Remarkably, all treatments reduced the severity of cardiac dysfunction and microcirculation hypoperfusion post-resuscitation compared to controls. Consistently, we observed alterations in the ferroptosis markers Glutathione peroxidase 4, 4-hydroxynonenal, and non-heme iron (1 ± 0.060 vs. 0.021 ± 0.016, 1 ± 0.145 vs. 3.338 ± 0.221, 52.010 ± 3.587 μg/g vs. 70.500 ± 3.158 μg/g, all P < 0.05) in the myocardium post-resuscitation. These changes were significantly attenuated by UAMC-3203 [(0.187 ± 0.043, 2.848 ± 0.169, all P < 0.05), (72.43 ± 4.920 μg/g, P > 0.05)] or Deferoxamine (0.203 ± 0.025, 2.683 ± 0.273, 55.95 ± 2.497 μg/g, all P < 0.05). In summary, UAMC-3203 and/or Deferoxamine improve PRMD and indicate the involvement of ferroptosis, suggesting that ferroptosis inhibitors could offer a novel therapeutic strategy for mitigating myocardial damage post-cardiopulmonary resuscitation.