Erythropoietin attenuates the tissue injury associated with hemorrhagic shock and myocardial ischemia.
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.
Abdelrahman
Maha
M
Centre of Experimental Medicine, Nephrology and Critical Care, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London EC1M 6BQ, United Kingdom.
Sharples
Edward J
EJ
McDonald
Michelle C
MC
Collin
Marika
M
Patel
Nimesh S A
NS
Yaqoob
Muhammad M
MM
Thiemermann
Christoph
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000517:prevention & control*
D004921:Erythropoietin