What is Hypoxia-Ischemia (HI)?

Hypoxia-ischemia (HI) is a condition characterized by inadequate oxygen supply (hypoxia) and reduced blood flow (ischemia) to tissues or organs in the body. It typically occurs when there is an imbalance between oxygen demand and oxygen delivery, resulting in tissue injury and dysfunction. Hypoxia-ischemia can affect various organs and tissues throughout the body, leading to a range of clinical manifestations and complications.


There are two main components of hypoxia-ischemia:


  • Hypoxia: Hypoxia refers to a state of reduced oxygen tension or availability in tissues, leading to cellular oxygen deprivation. Hypoxia can occur due to various factors, including reduced oxygen content in the blood (hypoxemia), impaired oxygen transport to tissues, or inadequate oxygenation of blood in the lungs. Cellular hypoxia disrupts aerobic metabolism and impairs cellular functions, ultimately leading to cellular injury and dysfunction.


  • Ischemia: Ischemia refers to a state of reduced blood flow and impaired perfusion to tissues or organs, leading to tissue hypoperfusion and oxygen deprivation. Ischemia can occur due to obstruction or narrowing of blood vessels, such as in the case of arterial occlusion, thrombosis, embolism, or vasoconstriction. Reduced blood flow deprives tissues of oxygen and nutrients, leading to cellular injury, metabolic dysfunction, and tissue damage.


Hypoxia-ischemia can occur in various clinical contexts, including:


  • Cerebral Hypoxia-Ischemia: Hypoxia-ischemia of the brain can lead to cerebral ischemia, stroke, or hypoxic-ischemic encephalopathy. It may result from conditions such as cardiac arrest, stroke, or respiratory failure.
  • Cardiac Hypoxia-Ischemia: Hypoxia-ischemia of the heart can lead to myocardial ischemia, angina pectoris, or myocardial infarction (heart attack). It may result from conditions such as coronary artery disease, atherosclerosis, or acute coronary syndrome.
  • Peripheral Hypoxia-Ischemia: Hypoxia-ischemia of peripheral tissues can lead to tissue necrosis, gangrene, or limb ischemia. It may result from conditions such as peripheral arterial disease, vascular occlusion, or traumatic injuries.


The severity and duration of hypoxia-ischemia determine the extent of tissue injury and the clinical consequences. Prolonged or severe hypoxia-ischemia can lead to irreversible tissue damage, organ dysfunction, and systemic complications.


What is the relationship between HI and oxidative stress?

The relationship between hypoxia-ischemia (HI) and oxidative stress involves complex interactions between cellular oxygen deprivation, ischemic injury, and the generation of reactive oxygen species (ROS) within tissues. Hypoxia-ischemia disrupts cellular metabolism, leading to oxidative stress and tissue damage through several mechanisms:


  • Mitochondrial Dysfunction: Hypoxia-ischemia impairs mitochondrial function, the primary site of ROS production in cells. Oxygen deprivation disrupts the electron transport chain and oxidative phosphorylation, leading to electron leakage and ROS generation. Mitochondrial dysfunction contributes to oxidative stress and amplifies tissue injury during hypoxia-ischemia.


  • Reactive Oxygen Species Production: Ischemic conditions induce the generation of ROS through multiple pathways, including activation of xanthine oxidase, NADPH oxidase, and mitochondrial enzymes. ROS, such as superoxide anion (O2•−), hydroxyl radical (•OH), and hydrogen peroxide (H2O2), are highly reactive molecules that can damage cellular components, including lipids, proteins, and DNA, leading to oxidative stress and tissue injury.


  • Inflammation and Immune Activation: Hypoxia-ischemia triggers an inflammatory response characterized by the release of pro-inflammatory cytokines, activation of immune cells, and recruitment of inflammatory mediators to the site of injury. Inflammatory cells, such as neutrophils and macrophages, produce ROS as part of the immune response to eliminate pathogens and damaged cells. However, excessive ROS production during inflammation overwhelms antioxidant defenses and exacerbates oxidative stress, further propagating tissue injury and inflammation.


  • Impaired Antioxidant Defenses: Hypoxia-ischemia disrupts cellular antioxidant defenses, leading to impaired scavenging of ROS and increased susceptibility to oxidative damage. Antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase normally neutralize ROS and protect against oxidative stress. However, during hypoxia-ischemia, antioxidant enzyme activity may be compromised due to depletion of cofactors, inhibition of enzyme function, or disruption of redox homeostasis, exacerbating oxidative stress and tissue injury.


  • DNA Damage and Cellular Injury: Oxidative stress induced by hypoxia-ischemia can cause damage to DNA, proteins, lipids, and other cellular components within tissues. ROS-induced DNA damage leads to genomic instability, activation of cell death pathways, and apoptosis or necrosis of affected cells. Cellular injury and death contribute to tissue damage, organ dysfunction, and systemic complications associated with hypoxia-ischemia.


Overall, oxidative stress plays a significant role in the pathogenesis and progression of tissue injury and organ dysfunction in hypoxia-ischemia.