3′,4′‐Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep

• Published in: British journal of pharmacology 2004-06, Vol.142 (3), p.443-452
• Main Authors: Wang, Sheng, Dusting, Gregory J, May, Clive N, Woodman, Owen L
• Format: Article
• Language: English
• Subjects: Animals; antioxidant; Antioxidants - administration & dosage; Antioxidants - therapeutic use; Biological and medical sciences; Cardiology. Vascular system; Coronary Circulation - drug effects; Coronary heart disease; Disease Models, Animal; Flavonoid; Flavonoids - administration & dosage; Flavonoids - therapeutic use; Heart; ischaemia; Medical sciences; Myocardial Contraction - drug effects; myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Neutrophil Infiltration - drug effects; nitric oxide; Nitric Oxide - metabolism; reperfusion; Sheep; Superoxides - metabolism; Time Factors
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705815

The antioxidant properties of flavonols in vivo and their potential benefits in myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We evaluated the ability of a synthetic flavonol, 3′,4′‐dihydroxyflavonol (DiOHF) to scavenge superoxide in post‐I/R myocardium and to prevent myocardial I/R injury. Anaesthetized sheep were studied in four groups (n=5–6): control, ischaemic preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg−1, i.v.). The left anterior descending coronary artery was occluded distal to the second diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial function, NADPH‐activated superoxide generation and biochemical markers of injury were measured. DiOHF (10−8–10−4 M) incubated in vitro with post‐I/R myocardium from the vehicle group suppressed superoxide production dose‐dependently. DiOHF administered in vivo also significantly reduced superoxide generation in vitro. DiOHF and IPC markedly reduced infarct size, which was 73±2% of the area at risk in vehicle, 50±4% in DiOHF, 75±5% in control and 44±4% in IPC. Post‐I/R segment shortening within the ischaemic zone was greater in DiOHF (2.3±0.7%; P