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Cardiovascular Research 2006 69(2):459-465; doi:10.1016/j.cardiores.2005.10.008
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Copyright © 2005, European Society of Cardiology

Enhanced efficiency of superoxide dismutase-induced cardioprotection by retrograde intracoronary administration

Satsuki Fukushima, Steven R. Coppen, Anabel Varela-Carver, Gemma Brindley, Kenichi Yamahara, Padmini Sarathchandra, Magdi H. Yacoub and Ken Suzuki*

Cell and Gene Therapy Group, Harefield Heart Science Centre, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, UK

* Corresponding author. Cell and Gene Therapy Group, Harefield Heart Science Centre, Harefield, Middlesex, UB9 6JH, UK. Tel.: +44 1895 453 846; fax: +44 1895 828 864. Email address: k.suzuki{at}ic.ac.uk

Objective: We hypothesized that modification of the infusion route may improve the efficiency of superoxide dismutase (SOD)-induced cardioprotection against reperfusion injury. The routes for SOD delivery previously examined were intravenous, via the left atrium, or by a combination of these, all of which can deliver SOD into the ischemic myocardium only after reperfusion. In contrast, retrograde intracoronary infusion may be able to deliver SOD before reperfusion. We investigated the feasibility and efficiency of the retrograde intracoronary infusion of SOD to attenuate reperfusion injury.

Methods and results: Lewis rats underwent 30-min left coronary artery occlusion followed by reperfusion for 24 h. Just before reperfusion, CuZn–SOD was administered intravenously (15,000 U/kg, V-SOD group) or by retrograde intracoronary infusion (1500 U/kg, R-SOD group) through a catheter inserted into left cardiac vein via left superior vena cava as we have previously reported. This method has been shown to perfuse the whole left ventricular free walls. Controls for each group were injected with phosphate buffer saline only via the same routes (V-PBS and R-PBS group). The R-SOD group demonstrated significantly preserved left ventricular ejection fraction (LVEF; 71.3 ± 1.7% vs. 60.8 ± 2.3%, p=0.028), reduced infarct size (23.3 ± 2.3% vs. 42.4 ± 3.5%, p<0.001), and attenuated polymorphonuclear leukocyte (PMNL) infiltration (11.8 ± 0.4 vs. 14.8 ± 0.2 103/mm2, p<0.001) compared to the V-SOD group. The V-SOD group demonstrated significantly improved reflow (64.3 ± 2.1% vs. 53.4 ± 2.4%, p=0.017) and attenuated PMNL infiltration (14.8 ± 0.2 vs. 16.8 ± 0.7 103/mm2, p=0.018) compared to the V-PBS group.

Conclusion: Retrograde intracoronary infusion is a promising, clinically applicable method to enhance the efficacy of SOD-induced myocardial protection against ischemia–reperfusion injury.

KEYWORDS Reperfusion injury; Free radicals; Cardioprotection; Acute inflammation; Retrograde intracoronary injection

Time for primary review 24 days


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