STUDIES OF HYPOXEMIC REOXYGENATION INJURY - WITHOUT AORTIC CLAMPING .3. COMPARISON OF THE MAGNITUDE OF DAMAGE BY HYPOXEMIA/REOXYGENATION VERSUS ISCHEMIA/REPERFUSION/

The immature heart is more tolerant to ischemia than the adult heart, yet infants with cyanosis show myocardial damage after surgical correc tion of congenital cardiac defects causing hypoxemia. This study teste d the hypothesis that the hypoxemic developing heart is susceptible to oxygen-mediated damage when it is reoxygenated during cardiopulmonary bypass and that this hypoxemic/reoxygenation injury is more severe th an ischemic/reperfusion stress. Fifteen Duroc-Yorkshire piglets (2 to 3 weeks old, 3 to 5 kg) underwent 60 minutes of 37 degrees C cardiopul monary bypass. Five piglets (control) were not made ischemic or hypoxe mic. Five underwent 30 minutes of normothermic ischemia (aortic clampi ng) and 25 minutes of reperfusion before cardiopulmonary bypass was di scontinued. Five others underwent 30 minutes of hypoxemia (bypass circ uit primed with blood with oxygen tension 20 to 30 mm Hg) and 30 minut es of reoxygenation during cardiopulmonary bypass. Functional (left-ve ntricular contractility) and biochemical (levels of plasma and tissue conjugated dienes and antioxidant reserve capacity) measurements were made before ischemia/hypoxemia and after reperfusion/reoxygenation. Ca rdiopulmonary bypass (no ischemia or hypoxemia) caused no changes in l eft-ventricular function or coronary sinus levels of conjugated dienes . The tolerance to normothermic ischemia was confirmed, inasmuch as le ft-ventricular function returned to 108% of control values and coronar y sinus levels of conjugated dienes did not rise after reperfusion, Co nversely, reoxygenation raised plasma levels of conjugated dienes in c oronary sinus blood in the hypoxic group 57% compared with end-hypoxic levels (p < 0.05 versus end-hypoxic levels and versus ischemia, by an alysis of variance), Antioxidant reserve capacity showed the lowest le vels (highest production of malondialdehyde) in the hypoxemic group (5 1% higher than control values; p < 0.05 by analysis of variance). Thes e biochemical changes were associated with a 62% depression of left-ve ntricular function after bypass because end-systolic elastance recover ed only 38% of control levels (p < 0.05 by analysis of variance), Thes e data confirm the tolerance of the immature heart to ischemia and rep erfusion and document a hypoxemic/reoxygenation injury that occurs in immature hearts reoxygenated during bypass. Hypoxemia seems to render the developing heart susceptible to reoxygenation damage that depresse s postbypass function and is associated with lipid peroxidation. These findings suggest that starting bypass in cyanotic immature subjects c auses an unintended reoxygenation injury that may potentially be count eracted by adding antioxidants to the prime of the extracorporeal circ uit.