PROTECTION OF RAT-HEART FROM ISCHEMIA-REPERFUSION INJURY BY THE 21-AMINOSTEROID U-74389G

In ischaemia-reperfusion syndromes lipid peroxidation appears an impor tant factor contributing to tissue damage. The 21-aminosteroids (lazar oids) exhibit beneficial effects in various pathological conditions, e specially in post-traumatic lesions of the central nervous system, whe re a peroxidative injury seems to be involved. The aim of our study wa s to ascertain if one of these compounds, U-74389G, plays a significan t role in protecting heart muscle from ischaemia-reperfusion damage. R at hearts used for heterotopic transplantation represented the experim ental model in this investigation. Animals (Wistar rats weighing 200-2 50 g) were divided into five groups: controls, untreated and treated d onors, untreated and treated recipients. Donors were anaesthetized and heparinized, and the heart was excised through a bilateral thoracotom y, arrested with St Thomas solution and stored in cold saline for 2 ho urs. For the recipient preparation, a modified One's technique was use d, and heart reimplantation was performed with a termino-lateral aorto -aortic anasthomosis and a termino-lateral pulmonary-cava anasthomosis . After the anasthomoses were completed hearts were reperfused for 30 min; then hearts were excised and specimens were taken for biochemical and morphological studies. These were conducted on three groups of he arts: (A) hearts reimplanted and reperfused without treatment of the d onor or of the recipient animal; (B) hearts subjected to the same proc edure but in the presence of U-74389G treatment of donors and recipien t rats; (C) control hearts rapidly excised from normal, non-operated a nimals. Electron microscopy studies showed, in hearts transplanted wit hout treatment, the typical morphological aspects of lipoperoxidative injury: swollen mitochondria with disrupted cristae, damaged endotheli al cells with the nucleous bulging into the lumen and a discontinued e ndothelial lining with diffuse oedema among the fibers. Lazaroid treat ment attenuated most of these damages in hearts of group B. As for the biochemical findings, the hearts transplanted in the presence of U-74 389G treatment had significantly higher ATP and creatine phosphate lev els (P<0.01) and lower malondialdehyde concentrations (P<0.05) with re spect to the hearts transplanted without treatment. Furthermore, serum creatine kinase activity was lower in treated than in untreated recip ient animals (P<0.05). Taken together, all these results indicate that U-74389G treatment is effective in protecting cardiac muscle from str uctural and functional ischaemia-reperfusion injuries, at least from t hose arising during a heart transplantation procedure. (C) 1996 The It alian Pharmacological Society