Because cardiac complications after myocardial infarction are more frequent in diabetics, we tested whether experimentally-induced diabetes may increase ischaemic myocardial injury in 23 rabbits, Diabetes was induced in randomized rabbits with the alloxan method. After 2 months, diabetic rabbits underwent a 30-min coronary occlusion followed by 3-h reperfusion and were compared with controls. Collateral Row was measured by the radioactive microsphere technique and infarct size by tetrazolium staining. Infarct size represented 28.6 +/- 4% of area-at risk in controls and 16.5 +/- 3% in diabetics (P<0.05), Collateral flow (0.06 +/- 0.03 ml/min/g in controls and 0.014 +/- 0.004 ml/min/g in diabetics) and area-at-risk: (50.2 +/- 4.2% of left ventricle in controls and 53.9 +/- 5.4% in diabetics) were similar in both groups. There was a significant positive correlation between area-at-risk and infarct size in both groups (r = 0.60 and 0.70, respectively) and for a given area-at-risk, diabetic rabbits developed smaller myocardial infarction than controls (covariance analysis, P<0.01). In additional experiments, hyperglycemia induced by intravenous glucose infusion in non-diabetic rabbits did not protect the ischaemic myocardium (infarct size: 37.9 +/- 12.5%). In conclusion, diabetes in the rabbit induces a chronic and metabolic form of preconditioning. Further studies are needed to explore the mechanism and time course of this protection. (C) 1998 Academic Press