title: Erythropoietin facilitates resuscitation from ventricular fibrillation by signaling protection of mitochondrial bioenergetic function in rats.
abstract: OBJECTIVE
  We previously reported beneficial myocardial effects during chest compression after administration of high-dose erythropoietin. We hypothesized that erythropoietin also elicits post-resuscitation myocardial benefits partly linked to protection of mitochondrial bioenergetic function.
  
  
  METHODS
  Two series of 10 rats each underwent ventricular fibrillation for 10 minutes (series-1) and 8 minutes (series-2) and were randomized to erythropoietin (5,000 U/kg) or 0.9% NaCl before chest compression. Dobutamine was infused post-resuscitation in series-2 harvesting their hearts at 120 minutes.
  
  
  RESULTS
  During chest compression, a statistically insignificant trend showing progressively higher coronary perfusion pressure in the erythropoietin group was observed consistent with previously reported preservation of left ventricular distensibility. Post-resuscitation, in the absence of dobutamine (series-1) erythropoietin failed to improve post-resuscitation myocardial function or survival; in the presence of dobutamine (series-2) all rats survived and those treated with erythropoietin reversed post-resuscitation myocardial dysfunction yielding higher cardiac work index (CWI; 39±3 vs 25±10 mmHg·ml/kg, p<0.01) and higher mean aortic pressure (MAP; 99±4 vs 83±16, p<0.01) at 120 minutes post-resuscitation. Better myocardial function was associated with lesser increases in plasma cytochrome c, attaining levels which inversely correlated with CWI (p=0.026) and MAP (p=0.025). Hearts from erythropoietin-treated rats had higher phosphorylation levels of cytosolic Akt and higher phosphorylation levels of cytosolic and mitochondrial PKCε and maintained cytochrome c oxidase activity.
  
  
  CONCLUSIONS
  Erythropoietin activated mitochondrial protective mechanisms that helped maintain bioenergetic function enabling reversal of post-resuscitation myocardial dysfunction in the presence of dobutamine.
authors: Department of Medicine and Resuscitation Institute at Rosalind Franklin University of Medicine and Science 3333 Green Bay Road, North Chicago, Illinois 60064, USA.
authors: Jeejabai
authors: J
authors: Radhakrishnan
authors: Madhav P
authors: MP
authors: Upadhyaya
authors: Matthew
authors: M
authors: Ng
authors: Ari
authors: A
authors: Edelheit
authors: Hawnyeu M
authors: HM
authors: Moy
authors: Iyad M
authors: IM
authors: Ayoub
authors: Raúl J
authors: RJ
authors: Gazmuri
keywords: Cardiopulmonary resuscitation; erythropoietin; mitochondrial function; myocardial function; rats; ventricular fibrillation
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