Resistin worsens cardiac ischaemia-reperfusion injury

We provide the first report of direct effects of resistin upon haemodynamic and neurohumoral parameters in isolated perfused rat heart preparations. Pre-conditioning with 1 nmol L−1 recombinant human resistin prior to ischaemia significantly impaired contractile recovery during reperfusion, compared with vehicle-infused hearts (P < 0.05, n = 12). This was accompanied by a significant increase in both A-type and B-type natriuretic peptides (P < 0.05, n = 12 both ANP and BNP vs vehicle), creatine kinase, and tumour necrosis factor-α (TNF-α) release in resistin-infused hearts. Resistin had no significant effect on myocardial glucose uptake. Co-infusion of resistin with Bay 11 7082 (an NF-κB inhibitor) improved contractile recovery following ischaemia and reduced both natriuretic peptide and creatine kinase release. This is the first evidence indicating resistin impairs cardiac recovery following ischaemia, stimulates cardiac TNF-α secretion, and modulates reperfusion release of natriuretic peptides and biochemical markers of myocardial damage. A TNF-α signalling related mechanism is suggested as one component underlying these effects.