Here we investigate the effects of
erythropoietin (EPO) on the tissue/organ injury caused by
hemorrhagic shock (HS), endotoxic
shock, and regional
myocardial ischemia and reperfusion in anesthetized rats. Male Wistar rats were anesthetized with
thiopental sodium (85 mg/kg i.p.) and subjected to
hemorrhagic shock (HS; i.e., mean arterial blood pressure reduced to 45 mmHg for 90 min, followed by
resuscitation with shed blood for 4 h),
endotoxemia (for 6 h), or left anterior descending coronary artery occlusion (25 min) and reperfusion (2 h). HS and
endotoxemia resulted in renal dysfunction and liver injury. Administration of EPO (300 IU/kg i.v., n = 10) before
resuscitation abolished the renal dysfunction and liver injury in hemorrhagic, but not endotoxic,
shock. HS also resulted in significant increases in the kidney of the activities of
caspases 3, 8, and 9. This increase in
caspase activity was not seen in HS rats treated with EPO. In cultured human proximal tubule cells, EPO concentration-dependently reduced the cell death and increase in
caspase-3 activity caused by either
ATP depletion (simulated
ischemia) or
hydrogen peroxide (oxidative stress). In the heart, administration of EPO (300 IU/kg i.v., n = 10) before reperfusion also caused a significant reduction in
infarct size. In cultured rat cardiac myoblasts (H9C2 cells), EPO also reduced the increase in DNA fragmentation caused by either serum deprivation (simulated
ischemia) or
hydrogen peroxide (oxidative stress). We propose that the acute administration of EPO on reperfusion and/or
resuscitation will reduce the tissue injury caused by
ischemia-reperfusion of the heart (and other organs) and
hemorrhagic shock.