RESUMO
ABSTRACT: Blocking ferroptosis reduces ischemia-reperfusion injury in some pathological contexts. However, there is no evidence that ferroptosis contributes to post-resuscitation myocardial dysfunction (PRMD). Here, we evaluated the therapeutic performance of ferroptosis inhibitors (UAMC-3203âor/and Deferoxamine) on the PRMD in a rat model of cardiac arrest and surveyed the changes of essential ferroptosis markers in the myocardium. Remarkably, all treatments reduce the severity of cardiac dysfunction and microcirculation hypoperfusion after resuscitation compared with control. Consistently, we observe that the ferroptosis marker Glutathione peroxidase 4, 4-hydroxynonenal and non-heme iron altered (1â±â0.060 vs. 0.021â±â0.016, 1â±â0.145 vs. 3.338â±â0.221, 52.010â±â3.587âug/g vs. 70.500â±â3.158âug/g, all Pâ<â0.05) in the myocardium after resuscitation. These changes were significantly suppressed by UAMC-3203 [(0.187â±â0.043, 2.848â±â0.169, all Pâ<â0.05), (72.43â±â4.920âug/g, Pâ >â0.05)], or Deferoxamine (0.203â±â0.025, 2.683â±â0.273, 55.95â±â2.497âug/g, all Pâ<â0.05). Briefly, UAMC-3203âor/and Deferoxamine improve post-resuscitation myocardial dysfunction and provide evidence of ferroptosis involvement, suggesting that ferroptosis inhibitors could potentially provide an innovative therapeutic approach for mitigating the myocardial damage caused by cardiopulmonary resuscitation.
