The effect of
neocuproine on cardiac injury was studied using retrogradely perfused isolated rat hearts in two experimental systems. In the first system, where
hydrogen peroxide-induced damage was studied,
neocuproine at the range of 40-175 microM provided protection at the level of 70-85%, as demonstrated by the reduced loss in the peak systolic pressure (P), in +dP/dt and in -dP/dt. In the second system, where
ischemia/reperfusion-induced arrhythmias were studied,
neocuproine (42 microM) provided a marked protection against cardiac injury as demonstrated by the lowering of the incidence in irreversible
ventricular fibrillation, by decreasing the duration of
ventricular fibrillation and by the concomitant increase of the duration of normal sinus rhythm, and by improving the post-ischemic recovery of P, +dP/dt and -dP/dt.
Free radicals have already been implicated as causative agents in cardiac injury resulting from either
hydrogen peroxide or
ischemia followed by reperfusion. Additionally,
iron and
copper have already been shown to drastically exacerbate the injurious effects of
free radicals. Thus, the results reported here with
neocuproine, a highly effective
chelator for both
iron and
copper, as well as with adventitious
copper and with the combination of
neocuproine and
copper, are in accord with the mediatory role of transition metals in enhancing the deleterious effects induced by
free radicals.