DEVELOPMENTAL DIFFERENCES IN SUPEROXIDE PRODUCTION IN ISOLATED GUINEA-PIG HEARTS DURING REPERFUSION

The production of free radicals on reperfusion has been implicated as an important factor governing post-ischemic recovery of cardiac functi on. Although the response of the heart to ischemia and reperfusion is known to change during cardiac development, it is not known if differe nt rates of free radical production play a role in these altered respo nses. The aim of this investigation was to determine if the production of the superoxide anion (O-2(-)) on reperfusion differs in the immatu re and mature heart. Immature hearts, obtained from 3-day premature gu inea pigs (delivered by cesarean section) were compared with those fro m adults (7 weeks old), Using the isolated Langendorff preparation. O- 2(-) production was measured during reperfusion following ischemic dur ations [0 (aerobic control), 15, 20, 30, and 60 min, n=6/group] by the reduction of succinylated ferricytochrome c in the perfusate, Both im mature and mature hearts exhibited a bell-shaped relationship between ischemic duration and peak O-2(-) production on reperfusion: (13.4 +/- 5.9: 22.2 +/- 5.4; 23.0 +/- 7.8; 59.3 +/- 16.2; 33.7 +/- 15.1, 32.6 /- 8.5 nmol/min/g wet weight in the immature heart and 15.7 +/- 1.9; 5 5.0 +/- 30.2; 82.8 +/- 14.0; 78.8 +/- 33.8; 40.6 +/- 16.4; 45.4 +/- 13 .1 nmolmin/g wet weight in the mature heart after 0; 15; 20; 30; 45 an d 60 min of ischemia, respectively), A similar relationship was also d emonstrated with total O-2(-) production over the 20-min reperfusion p eriod: (134.0 +/- 57.1: 106.5 +/- 46.2: 199.3 +/- 50.6; 362.0 +/- 99.5 ; 375.0 +/- 60.9; 221.0 +/- 73.0 nmol/20 min/g wet weight in the immat ure heart and 97.8 +/- 54; 282.0 +/- 139.0; 933.3 +/- 210.3; 964.0 +/- 374.0; 443.0 +/- 106.0; 352.0 +/- 1551.0 nmol/20 min/g wet weight in the mature heart after 0, 15, 20, 30, 45 and 60 min of ischemia, respe ctively). Mature hearts consistently produced more O-2(-) than immatur e hearts on reperfusion, while there was no significant difference in their capacity to produce O-2(-) during aerobic perfusion, We conclude that the immature heart may be at less risk from the free radical com ponent of reperfusion injury than the mature heart. (C) 1998 Academic Press.