P. Ferdinandy et al., ROLE OF NITRIC-OXIDE AND TPEN, A POTENT METAL CHELATOR, IN ISCHEMIC AND REPERFUSED RAT ISOLATED HEARTS, Clinical and experimental pharmacology and physiology, 25(7-8), 1998, pp. 496-502
1, The role of nitric oxide (NO) was studied in the control of ischaem
ic/reperfused cardiac function and the effect of N,N',N'-tetrakis-[2-p
yridylmethyl]-ethylenediamine (TPEN), a potent metal chelator, on the
regulation of cardiac NO formation, 2, Rat isolated working hearts wer
e subjected to 30 min ischaemia and reperfusion, The incidence of repe
rfusion-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 mu mol/L of TPEN administered prior to ischaemia, the
drug produced a reduction in the incidence of VF from its control val
ue 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 give
n 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 re
flected in the improvement of cardiac function both in the pre- and po
stischaemic TPEN-treated groups, 5, TPEN reduced basal cardiac NO cont
ent and prevented the accumulation of NO during ischaemia/reperfusion.
6, The results show that TPEN exerts beneficial effects on postischae
mic cardiac function and dysrhythmias in relation to inhibition of the
accumulation of NO in ischaemic/reperfused myocardium.