THE BLOOD CONTRIBUTION TO EARLY MYOCARDIAL REPERFUSION INJURY IS AMPLIFIED IN DIABETES

Cardiovascular disease is excessive in diabetes, and blood cell functi on is altered. It is not clear, however, if alterations in the blood c ontribute to the excessive cardiovascular complications of this diseas e. In this study, we compared the contribution of nondiabetic and diab etic blood to myocardial reperfusion injury. The recovery of cardiac c ontractile function following no-flow ischemia was studied in isolated diabetic and nondiabetic rat hearts perfused with diabetic or nondiab etic diluted whole blood. Hearts were isolated from 10- to 12-week-old diabetic (streptozotocin, 65 mg/kg, i.v.) and nondiabetic rats and pe rfused with a Krebs-albumin-red cell solution (K2RBC, Hct 20%). After a 30-min preischemic control period, during which cardiac pump functio n was evaluated, diabetic and nondiabetic hearts were perfused for 5 m in with diluted whole blood (DWB; Hct 20%) collected from either diabe tic or nondiabetic donor animals. Coronary flow was then stopped and t he hearts subjected to 30 min of no-flow ischemia. Following ischemia, the hearts were reperfused with the K2RBC perfusate. Cardiac contract ile function was evaluated throughout the 60-min reperfusion period. S ix groups were studied: diabetic and nondiabetic hearts perfused befor e ischemia with either K2RBC, nondiabetic DWB (NDDWB), or diabetic DWB (DDWB). Perfusion with DWB prior to ischemia impaired the recovery of contractile function in all cases. The impairment to recovery was gre ater with DDWB than with NDDWB. Although diabetic hearts perfused with K2RBC throughout recovered quite well, the effect of DDWB perfusion i n the diabetic hearts was dramatic. In an effort to determine why diab etic blood impaired functional recovery, measures of blood filterabili ty and the generation of reactive oxygen species (ROS) were made. We f ound that diabetic blood was less filterable than nondiabetic blood; t hat is, the diabetic blood cells tended to plug the 5-mu m filter pore s more readily than the nondiabetic blood cells. Also, we found that t he diabetic blood was capable of generating significantly greater ROS (oxygen free radicals) than nondiabetic blood (P < 0.05). These findin gs suggest that the blood contribution to myocardial reperfusion injur y is amplified in diabetes. A tendency for diabetic blood cells to plu g capillary-sized pores and show enhanced oxygen free radical producti on may account for the excessive contribution of diabetic blood to rep erfusion injury in the heart.