Effects of norepinephrine on hypoperfusion-reperfusion injuries in hearts isolated from normal and diabetic rats

Contractile and energy-metabolic functions were investigated in paced hearts isolated from normal (Normal) and streptozotocin-diabetic rats (DM) during hypoperfusion at 1 ml/min with or without 10(-6) M norepinephrine (NE) and during reperfusion at the pre-hypoperfusion flow. Left ventricular pressure (LVP) and contractile force (CF) were monitored, respectively, through a water-filled balloon in LV and through a hook attached to the apex. A 1-h hypoperfusion without NE caused significant elevations in resting LVP and resting CF only in DM hearts, smaller transmural lactate accumulations in DM hearts, and similar ATP decreases in both groups. Significant decreases in developed LVP and developed CF were observed in both groups. NE during hypoperfusion caused deterioration of these cardiac dysfunctions in both groups, particularly in DM hearts. A 1-h reperfusion caused elevations in resting LVP and resting CF with no recovery in developed CF in Normal hearts, while it caused partial recovery in resting and developed CF in DM hearts. Both groups showed similar partial recovery of ATP. NE during hypoperfusion improved the mechanical dysfunction during reperfusion in DM hearts, but there was a smaller recovery in ATP than in hearts without NE. In vivo insulin treatment in DM restored the cardiac functions to Normal levels. Thus, DM hearts were more vulnerable to hypoperfusion, while Normal hearts were more vulnerable to reperfusion injury.