Timing of Erythropoietin Treatment for Cardioprotection in Ischemia/Reperfusion

Abstract

Erythropoietin (EPO) is a hormone known to stimulate hematopoiesis. However, recent research suggests additional properties of EPO, such as protection against ischemia/reperfusion (I/R) injury in various tissues. We studied the effect of timing of EPO administration on cardioprotection during I/R in the heart. Male Sprague-Dawley rats were subjected to 45 minutes of coronary occlusion, followed by 24 hours of reperfusion. Animals were randomized to receive saline or single dose of EPO (5,000 IU/kg) either 2 hours before I/R, at the start of ischemia, or after the onset of reperfusion. The ratio of infarct area/area at risk (planimetry), left ventricular (LV) function (pressure development), and apoptosis (number of active caspase-3 positive cells) were determined after 24-hour reperfusion. Administration of EPO during different time points resulted in a 19 to 23% (P < 0.05) reduction in the infarct area/area at risk, which was accompanied by a trend toward better LV hemodynamic parameters. Apoptosis was significantly attenuated in groups treated with EPO at the start of ischemia (29% reduction) and after the onset of reperfusion (38%), and to a lesser extent (16%) in the group pre-treated with EPO. Thus, in vivo administration of EPO at different time points protects the myocardial structure and preserves cardiac function during I/R. Cardioprotective effect of EPO is associated with inhibition of apoptosis.

Integrin-Linked Kinase Is Required in Hypoxic Mesenchymal Stem Cells for Strengthening Cell Adhesion to Ischemic Myocardium

“…Cell implantation utilizing cardiac stem cells [18], embryonic stem cells [19], hematopoietic stem cells [20], MSCs [21][22][23], skeletal myoblasts [24][25][26], and cardiac myocytes (adult, fetal, or neonatal myocytes) [27,28] has been suggested to be a promising clinical approach for restoration of myocardial function after cardiac infarction. Among these various candidate cell types, MSCs have a great advantage with respect to generating functional cardiac myocytes in the infarcted myocardium because of their ease of preparation and potential to differentiate into a cardiac lineage [29,30] both in vivo and in vitro under appropriate culture conditions.…”

A nonerythropoietic derivative of erythropoietin protects the myocardium from ischemia–reperfusion injury

“…However, it is currently unknown what schedule of dosing will result in maximum tissue salvage. In a recent limited time-window study using EPO, administration at the time of cardiac reperfusion was associated with a better outcome than when given 2 h before (32). However, given the prolonged time course of ventricular remodeling and development of heart failure and its association with continued cardiomyocyte apoptosis (reviewed in refs.…”

Erythropoietin Protects the Intestine Against Ischemia/Reperfusion Injury in Rats

“…EPO was found to have a beneficial effect on intestinal damage such as colitis (12), necrotizing enterocolitis, (13) and anastomosis (14) in animal models. Previous studies have shown that EPO exhibits protective effects on tissue injury associated with I/R in many tissues such as cardiac (15), kidney (16), liver (17), lung (18), brain (19), and retina (20). However, it is not known whether EPO has a protective effect in the intestinal injury associated with I/R.…”