The reoxygenation injury: Is it clinically important?

Abstract

Repair of cyanotic congenital heart defects necessitating cardiopulmonary bypass (CPB) is becoming more frequent in infants and neonates. Despite apparently successful surgical correction, postoperative myocardial and pulmonary dysfunction continues to be a major contributor to morbidity and mortality and is more severe than after repair of acquired defects in adults with normoxic conditions. [1][2][3] The neonatal heart also has a reduced response to inotropic agents compared with the adult heart. 1,2 Thus, preservation of myocardial function in neonates during cardiac operations assumes even greater importance, because a perioperative insult is less well tolerated and more difficult to treat.Congenital malformations of the heart frequently lead to physiologic abnormalities ("stress") that are quite different from those seen in the adult, and so the concerns during CPB are not necessarily the same. The most common preoperative stress in adults is ischemia, secondary to coronary artery disease, and the major concern is avoidance of a "regional" myocardial reperfusion injury with the reintroduction of blood. 4 In contrast, the most common preoperative stress in pediatric patients is hypoxia (cyanosis). 1,2 The major concern, therefore, is whether a reoxygenation injury (similar to a reperfusion injury) occurs with the abrupt reintroduction of oxygen. The occurrence of such an injury could be even more detrimental, as it would result in "global "damage, since hypoxia affects the entire body, not just the heart.Acute hypoxia and acidosis may occur as a consequence of many congenital heart defects and can result in depletion of glycogen, adenosine triphosphate, and Krebs cycle intermediates, leading to myocardial dysfunction. 2,5,6 Significant acute hypoxia forces the myocardium to rely on anaerobic metabolism, and when acidosis is present, this further heightens these deleterious effects. Chronic hypoxia leads to cyanosis, a condition frequently encountered in infants and children undergoing cardiac operations. Despite compensatory mechanisms, substrate depletion and metabolic derangements are more common in cyanotic hearts than in normoxic hearts. [1][2][3]5,6 Moreover, cyanosis depletes the myocardium of endogenous antioxidants, and a growing body of experimental and clinical evidence indicates that this may make the cyanotic immature heart more susceptible to an oxygen-mediated injury when molecular oxygen is restored. [7][8][9][10] The reversal of hypoxemia occurs with initiation of extracorporeal circulation and precedes the surgical ischemia used for operative repair in children with cyanotic disease. The conventional method of starting CPB in infants and children with hypoxemia is to abruptly raise oxygen tension (Po 2 ) to approximately 400 to 500 mm Hg. Does this sudden reintroduction of oxygen causes a significant "unintended injury" and, if so, can it be prevented? Such an injury might explain why the cyanotic heart is more vulnerable and less tolerant to subsequent surgical ischemia than the normoxic hea...

Arrhythmogenesis in the Developing Heart During Anoxia‐Reoxygenation and Hypothermia‐Rewarming: An In Vitro Model

“…Throughout the embryonic and fetal periods, brief or prolonged reduction in oxygen availability can lead to cardiac dysfunction and, consequently, abnormal development of the whole fetus. As the tolerance to hypoxia is different in the developing and the adult heart, 7 various animal models of embryonic, 8 fetal, 9 and neonatal hearts 10 have been used to investigate the response to hypoxia/reoxygenation (or ischemia/reperfusion) and to improve specific protective strategies.…”

Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide

“…This might be achieved by lowering the O 2 ‐concentration during resuscitation. There is therefore an ongoing debate regarding whether resuscitation of the newborn should be performed with ambient air or 100% O 2 [9–14]. Hyperoxia is thought to increase the production of reactive oxygen species and disrupt the antioxidant mechanisms [15,16].…”

Myocardial Protection in Neonates and Infants: What have we Learnt? Where do we Go?

“…A hot shot is warm, K + containing cardioplegia solution enriched with substrates like histidine, glutathione aspartate which is given prior to releasing the aortic cross clamp and provides to heart along with oxygen and substrates for myocardial recovery.The immature heart is less tolerant to reperfusion injury compared to adult heart [53]. Use of warm substrate-enhanced reperfusate (hot shot) in conjunction with leukocyte depletion and filtration has been useful in preventing reperfusion injury in children [53].…”

“…Use of warm substrate-enhanced reperfusate (hot shot) in conjunction with leukocyte depletion and filtration has been useful in preventing reperfusion injury in children [53].…”