Role of nitric oxide and TPEN, a potent metal chelator, in ischaemic and reperfused rat isolated hearts.

1. The role of nitric oxide (NO) was studied in the control of ischaemic/reperfused cardiac function and the effect of N,N,N',N'-tetrakis-[2-pyridylmethyl]-ethylenediamine (TPEN), a potent metal chelator, on the regulation of cardiac NO formation. 2. Rat isolated working hearts were subjected to 30 min ischaemia and reperfusion. The incidence of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT) and the recovery of cardiac function were measured. Nitric oxide was detected by electron spin resonance (ESR) spectroscopy. 3. With 5.0, 7.5 and 10.0 mumol/L of TPEN administered prior to ischaemia, the drug produced a reduction in the incidence of VF from its control value of 100% to 25% (P < 0.05), 17% (P < 0.05) and 8% (P < 0.05), respectively. The incidence of VT followed the same pattern. 4. When TPEN was given at the moment of reperfusion, a reduction in the incidence of VF and VT was still observed. Reduction in the incidence of VF and VT was reflected in the improvement of cardiac function both in the pre- and post-ischaemic TPEN-treated groups. 5. TPEN reduced basal cardiac NO content and prevented the accumulation of NO during ischaemia/reperfusion. 6. The results show that TPEN exerts beneficial effects on postischaemic cardiac function and dysrhythmias in relation to inhibition of the accumulation of NO in ischaemic/reperfused myocardium.