OBJECTIVE: A proposal that injury in ischaemic/reperfused rat heart is critically dependent on the availability of free iron rather than on the efficiency of O2-. and H2O2 production was examined. METHODS: Isolated working rat hearts from 152 male Wistar rats (200-250 g weight), subjected to 20-40 min of global ischaemia and reperfused for 30 min, were perfused with 10 mumol.litre-1 Fe[III] or Fe[II] and/or 0.6 mmol.litre-1 desferrioxamine, 10 mmol.litre-1 dimethylthiourea, and 1 mmol.litre-1 allopurinol. Curves relating the recoveries of haemodynamic functions and the reperfusion lactate dehydrogenase release to the duration of the preceding ischaemic period were constructed. Morphological examination was also performed. RESULTS: In the untreated hearts, the duration of ischaemia resulting in 50% loss of cardiac output was 29 min. This time was decreased to 24 min and 20 min by Fe[III] and Fe[II], respectively, and was increased to 36 min and 37 min by desferrioxamine and dimethylthiourea, respectively. Desferrioxamine prevented the effect of Fe[III] but not that of Fe[II], whereas dimethylthiourea prevented the effect of Fe[II]. Neither the effect of Fe[III] nor that of Fe[II] was prevented by allopurinol which, however, proved to be beneficial in the untreated hearts. CONCLUSIONS: The beneficial effect of desferrioxamine and dimethylthiourea suggest that it is intensification of the Fenton reaction by iron which accounts for iron induced aggravation of the reperfusion injury. Thus we speculate that the availability of free iron, rather than O2-. and H2O2, is a limiting factor in the development of injury in an ischaemic/reperfused rat heart. What remains unclear is why allopurinol is unable to prevent iron induced changes.
OBJECTIVE: A proposal that injury in ischaemic/reperfused rat heart is critically dependent on the availability of free iron rather than on the efficiency of O2-. and H2O2 production was examined. METHODS: Isolated working rat hearts from 152 male Wistar rats (200-250 g weight), subjected to 20-40 min of global ischaemia and reperfused for 30 min, were perfused with 10 mumol.litre-1 Fe[III] or Fe[II] and/or 0.6 mmol.litre-1 desferrioxamine, 10 mmol.litre-1 dimethylthiourea, and 1 mmol.litre-1 allopurinol. Curves relating the recoveries of haemodynamic functions and the reperfusion lactate dehydrogenase release to the duration of the preceding ischaemic period were constructed. Morphological examination was also performed. RESULTS: In the untreated hearts, the duration of ischaemia resulting in 50% loss of cardiac output was 29 min. This time was decreased to 24 min and 20 min by Fe[III] and Fe[II], respectively, and was increased to 36 min and 37 min by desferrioxamine and dimethylthiourea, respectively. Desferrioxamine prevented the effect of Fe[III] but not that of Fe[II], whereas dimethylthiourea prevented the effect of Fe[II]. Neither the effect of Fe[III] nor that of Fe[II] was prevented by allopurinol which, however, proved to be beneficial in the untreated hearts. CONCLUSIONS: The beneficial effect of desferrioxamine and dimethylthiourea suggest that it is intensification of the Fenton reaction by iron which accounts for iron induced aggravation of the reperfusion injury. Thus we speculate that the availability of free iron, rather than O2-. and H2O2, is a limiting factor in the development of injury in an ischaemic/reperfused rat heart. What remains unclear is why allopurinol is unable to prevent iron induced changes.
Authors: S Pucheu; F Boucher; T Sulpice; N Tresallet; Y Bonhomme; B Malfroy; J de Leiris Journal: Cardiovasc Drugs Ther Date: 1996-07 Impact factor: 3.727