Cardioprotective effects of erythropoietin on postresuscitation myocardial dysfunction in appropriate therapeutic windows

Objective: Erythropoietin has been noted for its cardioprotective effects. The objective of the study is to investigate its effects on postresuscitation myocardial dysfunction and therapeutic windows. Design: Randomized animal study. Setting: Animal research laboratory. Subjects: Adult male adult Wistar rats. Interventions: Cardiopulmonary resuscitation was started after 6.5 or 9.5 mins of asphyxia-induced cardiac arrest. The resuscitated animals received either erythropoietin (1000, 3000, or 5000 U/kg) or placebo intravenously 3 mins after return of spontaneous circulation. Measurements and Main Results: Erythropoietin treatment improved the 3-day survival and left ventricular dP/dt(40) and peak negative dP/dt after, 6.5 mins asphyxia-induced cardiac arrest. The cardioprotective effects of erythropoietin decreased after 9.5 mins asphyxia-induced cardiac arrest with worse postresuscitation left ventricular dP/dt(40) and peak negative dP/dt (p < .01 for both). The erythropoietin showed a dose-dependent response for its cardioprotective effects. The 3-day survival rates were higher in the group treated with erythropoietin 5000 U/kg than with 3000 and 1000 U/kg groups (p = .045 and .003, respectively). Postresuscitation left ventricular dP/dt(40) and peak negative dP/dt were more preserved in the group treated with erythropoietin 5000 U/kg than the groups with lower doses (p < .05 for both). Conclusions: Erythropoietin has the potential to improve postresuscitation myocardial dysfunction and short-term survival in appropriate therapeutic windows. (Crit Care Med 2008; 36[Suppl.]: S467-S473)