Editorial – Hypoxia and Reoxygenation: From Basic Science to Bedside

Citation: Samaja M and Milano G (2015) Editorial – Hypoxia and reoxygenation: from basic science to bedside. A condition with inadequate oxygen supply to the tissues, hypoxia plays a pivotal role in the pathology of cyanotic congenital heart defects and several adult diseases as myocardial infarction, stroke, cancer, diabetes, aging, and pulmonary obstruction. Most cell responses to hypoxia are modulated by hypoxia-inducible factors [HIFs (1)], DNA-binding transcription factors that mediate hypoxia adaptation through activation of a multitude of genes encoding proteins needed to improve tissue oxygen delivery, energy metabolism, efficient management of hypoxia-induced stress and regulation of apoptosis, autophagy, and cell cycle. The reoxygenation that follows hypoxia usually induces bursts of reactive oxygen species, which not only cause the oxidative damage central in the pathophysiol-ogy of hypoxia/reoxygenation (HReox) injury but also activate signaling mechanisms that in part synergize and in part oppose those induced by hypoxia. Consequently, it becomes often difficult to distinguish what is attributable to hypoxia and what to the reoxygenation that follows hypoxia. A new research frontier may foster clues to understand the mechanisms underlying HReox injury and to identify appropriate targets to design interventions aimed at reducing the toll of this injury in several diseases. One example is paradigmatic. For many years, hypoxia was believed to be associated with car-dioprotection. However, it is now evident that it is not hypoxia, but HReox, the factor providing cardioprotection (2), or hypoxic preconditioning (3). In hearts exposed to hypoxia, alterations in several signaling paths (4, 5) converge into deleterious phenotypes as right ventricular hypertrophy and impaired ability to resist ischemia/reperfusion (6). These findings are corroborated by the clinical observation that the outcome of surgery for repair of cyanotic congenital heart defects is complicated by myocardial damage due to HReox at the moment of the institution of cardiopulmonary bypass with elevated oxygen content, followed by ischemia/reperfusion injury when heart is arrested to perform the intra-cardiac repair (7). HReox is related to the intermittent hypoxia (IH) paradigm, e.g., repeated exposure to short periods of hypoxia 5–10 times/day. Although displaying protective features in the favor of musculoskeletal, pulmonary, central nervous, and cardiopulmonary systems (8), IH may have Janus-like features (9): on the one hand, IH is a form of hypoxic preconditioning (10); on the other hand, it may become dangerous and pave the road to obstructive sleep apnea syndrome (OSAS) (11, 12), which causes harmful redox stress (13). The purpose of this …