Role of insulin receptors in myocardial ischaemia-reperfusion injury during cardiopulmonary bypass.

Abstract

Ischaemia-reperfusion injury after cardiac bypass causes cardiac dysfunction and tissue damage. Insulin resistance during reperfusion contributes to the dysfunction, but the role of changes in myocardial insulin receptors during this period has not been determined yet. Twelve mongrel dogs underwent cardiac bypass, 6 for 30 min and 6 for 120 min. Blood samples were taken from the coronary artery and coronary sinus and tissue samples from the apex of the left ventricle before bypass and 15, 45, and 75 min after termination of bypass surgery and initiation of reperfusion. Plasma glucose and insulin, the Insulin Resistance Index, myocardial glycogen, insulin receptor alpha and beta subunits, and total insulin mRNA were measured in these samples. Plasma glucose and insulin and the insulin resistance index all increased significantly during the reperfusion period. A significant decrease in myocardial glycogen occurred at the same time. The alpha subunits of the insulin receptor were seen on the myocyte surface and the beta subunits mostly in the cytoplasm.The expression of both subunits and total insulin mRNA decreased in a similar manner after termination of bypass surgery. All parameters gradually returned toward pre-bypass values as the post-bypass period progressed. And at all post-bypass time points, the 120-min bypass group showed a significantly greater effect from ischaemia than the 30-min bypass group. A decrease in insulin receptor expression is a cause of post-bypass insulin resistance, and this decrease is initiated at the mRNA level. Increased insulin resistance leads to excessive reliance on myocardial glycogen as an energy source and a deficit in energy substrates that contributes to cardiac dysfunction.