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 function. Although the response of the heart to ischemia and reperfusion is known to change during cardiac development, it is not known if different rates of free radical production play a role in these altered responses. The aim of this investigation was to determine if the production of the superoxide anion (O2−) on reperfusion differs in the immature and mature heart. Immature hearts, obtained from 3-day premature guinea pigs (delivered by cesarean section) were compared with those from adults (7 weeks old). Using the isolated Langendorff preparation. O2−production was measured during reperfusion following ischemic durations [0 (aerobic control), 15, 20, 30, and 60 min,n=6/group] by the reduction of succinylated ferricytochrome c in the perfusate. Both immature and mature hearts exhibited a bell-shaped relationship between ischemic duration and peak O2−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; 55.0±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 and 60 min of ischemia, respectively). A similar relationship was also demonstrated with total O2−production over the 20-min reperfusion period: (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 immature 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, respectively). Mature hearts consistently produced more O2−than immature hearts on reperfusion, while there was no significant difference in their capacity to produce O2−during aerobic perfusion. We conclude that the immature heart may be at less risk from the free radical component of reperfusion injury than the mature heart.