Improvement of doxorubicin induced cardiomyopathy in rats treated with insulin-like growth factor I

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Abstract
Objectives: This study was designed to assess the effects of treatment with insulin-like growth factor-I (IGF-I) on cardiac function and structure in rats with an established cardiomyopathy. Methods: Adult male Wistar rats were injected with doxorubicin (2 mg·kg−1 subcutaneously) weekly for 12 weeks and either rhIGF-I (0.8 mg·kg−1·day−1; n=16, D-I group) or saline (n=25, D-S group) subcutaneously via an osmotic pump from weeks 9 to 12. A non-doxorubicin injected control group was also studied. After 12 weeks survivors were anaesthetised and cardiac output determined with radiolabeled microspheres. At postmortem pleural effusion and ascitic volumes were measured and the heart was removed for histological examination by light and transmission electron microscopy. Results: Doxorubicin treated animals showed less mean weight gain from week 2 than the untreated control group. Animals treated with IGF-I from week 9 showed a significant (pv 91.4(6.4) ml·min−1, pv 0.226(0.02) ml, pConclusions: Administration of IGF-I may improve the function of damaged myocardium, although the mechanisms are unclear. Further studies with earlier coadministration of IGF-I, quantitative histological analysis, and with other models of cardiac injury are indicated. Cardiovascular Research 1993;27:1368-1373

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