Epidermal growth factor protects the heart against low-flow ischemia-induced injury

Abstract

The role of ErbB4 and ErbB2 in the heart of adult mammals is well established. The heart also expresses ErbB1 (the epidermal growth factor (EGF) receptor), but this receptor has received less attention. We studied the effect of EGF on the response of isolated mouse heart to low-flow ischemia and reperfusion. Reducing perfusate flow to 10% for 30 min resulted in an increase in anaerobic metabolism and the leakage of lactate dehydrogenase during reperfusion. In addition, left ventricle +dP/dt and developed pressure were depressed (20-25%) during reperfusion. The addition of EGF 5 min before and throughout the ischemic period prevented the increase in anaerobic metabolism and the leakage of intracellular lactate dehydrogenase during reperfusion. EGF improved both +dP/dt and developed pressure during ischemia and prevented the decrease in dP/dt during reperfusion. To determine whether the effect of EGF on cell integrity depends on its effect on contractility, we studied nonbeating isolated myocytes. In these cells, anoxia and reoxygenation reduced cell viability by nearly 25%. EGF prevented such a decrease. Our results indicate that, like ErbB4 and ErbB2, ErbB1 also has an important role in the heart of adult animals.