Improvement of Hypoperfusion with Norepinephrine Injury by Ex Vivo Insulin in Isolated Diabetic Rat Hearts

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Effects of insulin on contractile and energy metabolic dysfunctions during hypoperfusion (2 ml/min/g heart wt., 60 min) with 10^-6 M norepinephrine were studied in paced hearts isolated from streptozotocin-diabetic rats. Insulin (2 mU/ min/g heart wt.) was infused 20 min before and during hypoperfusion (pre-treated group) or 30 min after the onset of hypoperfusion (post-treated group). Hearts in the non-treated group were hypoperfused without insulin and other hearts in the control group were not hypoperfused. In the non-treated group, resting contractile force (CF) and resting left ventricular pressure (LVP) were significantly elevated to maximum levels within 30 min after hypoperfusion and these elevations were restored in the pre-treated group but not in the post-treated group. Developed CF was depressed in the non-treated group and improved significantly in the pretreated group but not in the post-treated group. Developed LVP was depressed in the non-treated group, and depression was slightly larger in the pre-treated group. In the non-treated group, ATP and creatine phosphate contents in the left ventricle significantly decreased. Decreases in ATP and creatine phosphate contents in the inner layer were partially restored in the pre-treated group but not in the posttreated group. Lactate significantly increased in the non-treated group and increased even further in the insulin treated groups. These results indicate that contractile dysfunction during hypoperfusion with norepinephrine is improved by pre-treated insulin, as is partial recovery of energy metabolism.