TOLERANCE OF THE DEVELOPING HEART TO ISCHEMIA - IMPACT OF HYPOXEMIA FROM BIRTH

Many infants who require cardiac surgery have cyanotic heart disease. We assessed the relative tolerances to ischemia of hearts from immatur e normoxemic rabbits versus hearts from immature rabbits subjected to hypoxemia since birth. Normoxemic animals were raised from birth in an environment where the inspired fractional concentration of oxygen (F- IO2) was 0.21; for the hypoxemic studies F-IO2 was reduced to 0.09. He arts (n = 6/group) from normoxemic and chronically hypoxemic rabbits a t 7-12, 21-28, 35-44, and 51-56 days of age underwent aerobic ''workin g'' perfusion with Krebs bicarbonate buffer, and cardiac function was measured. Hearts were then arrested by a 3-min infusion with either co ld (14 degrees C) Krebs buffer (hypothermia alone group) or St. Thomas ' Hospital II solution (hypothermia plus cardioplegia group) before 6 h of hypothermic (14 degrees C) global ischemia. Hearts were reperfuse d, and postischemic creatine kinase leakage and recovery of function w ere measured. For hearts protected with hypothermia alone, recovery of aortic flow was better in hearts hyperemic from birth compared with n ormoxemic controls at 7-12 days (78 +/- 7 vs. 60 +/- 6%, P < 0.05) and 21-28 days old (81 +/- 12 vs. 26 +/- 28%, P < 0.05). Protection with hypothermia plus cardioplegia was also better in hearts hypoxemic from birth compared with normoxemic controls at 7-12 days (74 +/- 8 vs. 63 +/- 10%, P < 0.05) and 21-28 days old (84 +/- 3 vs. 71 +/- 5%, P < 0. 05). Protection with hypothermia alone and hypothermia plus cardiopleg ia was no different within chronically hypoxemic age groups. In normox emic animals, protection with hypothermia alone gradually declined wit h increasing age, while protection with hypothermia plus cardioplegia progressively increased with age. Immature myocardium hypoxemic from b irth was more tolerant of ischemia than normoxemic myocardium during e arly stages of postnatal development when protected with either hypoth ermia alone or hypothermic St. Thomas' II solution. This early protect ive effect was rapidly lost as the chronically hypoxemic rabbit mature d.