Deferoxamine infusion during coronary artery bypass grafting ameliorates lipid peroxidation and protects the myocardium against reperfusion injury: immediate and long-term significance.

ABSTRACT

AIMS: Previous reports have demonstrated enhanced myocardial protection and better post-ischaemic recovery using the oxygen free radical scavenger deferoxamine (DEF) during cardioplegia. The aim of this study was to test whether, in patients undergoing coronary artery bypass grafting (CABG), DEF i.v. infusion can reduce reperfusion injury on a short- and long-term basis. METHODS AND RESULTS: Forty-five consecutive male patients were randomly allocated to two groups in group D (n=25, age 60.8+/-8.6 years), 4 g of DEF were infused for 8 h starting immediately after the induction of anaesthesia; in group C (n=20, age 62.2+/-6.4 years) dextrose solution was given for the same time as placebo. Haemodynamic monitoring and measurement of oxygen free radical production [by measuring thiobarbituric acid reactive substances (TBARS)] were carried out before and after CABG. Left ventricular ejection fraction (EF) and wall motion score index (WMSI) were measured before and after CABG and 12 months later. Haemodynamic measurements were similar in both groups before and after CABG. TBARS peaked at 4.8+/-1.1 nmol/mL in group C, but remained unchanged (2.4+/-0.9 nmol/mL) in group D (P=0.01). At baseline, both the EF and WMSI were similar between the groups. Following CABG, EF increased more in group D (8.8+/-8.4%) than in group C (1.3+/-6.7%), P=0.008, while WMSI decreased more in group D (-0.7+/-0.3) than in group C (-0.2+/-0.2), P=0.0001. Dividing group D according to the pre-operative median EF value (38%), we observed that after 1 year follow-up, DEF infusion conferred more protection in patients with a lower EF (EF increased by 19.3+/-6.2%, WMSI decreased by -1.1+/-0.2) than in those with a higher EF (EF increased by 7.7+/-4.5%, WMSI decreased by -0.8+/-0.2), P=0.001, respectively. CONCLUSION: In patients undergoing CABG, DEF i.v. infusion ameliorates oxygen free radical production and protects the myocardium against reperfusion injury. Patients with a lower EF seem to benefit more by DEF i.v. infusion.