Hypoxia-dependent signaling in perioperative and critical care medicine

Abstract

A critical goal of patient management for anesthesiologists and intensivists is to maintain oxygen homeostasis in patients admitted to operation theaters and intensive care units. For this purpose, it is imperative to understand the strategies of the body against oxygen imbalance—especially oxygen deficiency (hypoxia). Adaptation to hypoxia and maintenance of oxygen homeostasis involve a wide range of responses that occur at different organizational levels in the body. These responses are greatly influenced by perioperative patient management including factors such as perioperative drugs. Herein, the influence of perioperative patient management on the body's response to oxygen imbalance was reviewed with a special emphasis on hypoxia-inducible factors (HIFs), transcription factors whose activity are regulated by the perturbation of oxygen metabolism. The 2019 Nobel Prize in Physiology or Medicine was awarded to three researchers who made outstanding achievements in this field. While previous studies have reported the effect of perioperatively used drugs on hypoxia-induced gene expression mediated by HIFs, this review focused on effects of subacute or chronic hypoxia changes in gene expression that are mediated by the transcriptional regulator HIFs. The clinical implications and perspectives of these findings also will be discussed. Understanding the basic biology of the transcription factor HIF can be informative for us since anesthesiologists manage patients during the perioperative period facing the imbalances the oxygen metabolism in organ and tissue. The clinical implications of hypoxia-dependent signaling in critical illness, including Coronavirus disease (COVID-19), in which disturbances in oxygen metabolism play a major role in its pathogenesis will also be discussed.

The incidence and risk factors of perioperative cardiac complications in noncardiac major surgery in high-altitude areas: A prospective trial in Tibet autonomous region, China

“…The hypoxic environment in high-altitude areas leads to a decrease in arterial partial pressure of oxygen (PaO 2 ) and pulse oxygen saturation (SpO 2 ). Long-term exposure to chronic hypoxia can cause pulmonary arterioles to contract, which leads to pulmonary artery hypertension (PAH) and increased right ventricular load ( 6 , 7 ). In addition to cardiac overload, the incidences of hyperhemoglobinemia, hyperlipemia, and hypercoagulability are also higher than those found in patients living in plain areas ( 8 ).…”

Role of hypoxia-inducible factor in postoperative delirium of aged patients: A review

“…[10–15] HIF-1 may have a protective role in regulating neuron apoptosis in neonatal hypoxia-ischemia brain damage and may promote the repair and rebuilding process in the brain that was damaged by hypoxia and ischemia. [10] Animal experiments show that neuron-specific loss of HIF-1 increases ischemic brain injury, and the recovery of neural function in ischemic rats is related to the increased expression of hypoxia-inducible factor subtype 1α (HIF-1α). [10,11] And more recently, anesthetics and perioperative drugs have been reported to affect HIF-1 activity.…”

“…[4][5][6] Hypoxia stimulates the expression of hypoxia-inducible factor-1 (HIF-1), which controls the hypoxic response. [10][11][12][13][14][15] HIF-1 may have a protective role in regulating neuron apoptosis in neonatal hypoxia-ischemia brain damage and may promote the repair and rebuilding process in the brain that was damaged by hypoxia and ischemia. [10] Animal experiments show that neuron-specific loss of HIF-1 increases ischemic brain injury, and the recovery of neural function in ischemic rats is related to the increased expression of hypoxia-inducible factor subtype 1α (HIF-1α).…”

“…[10] Animal experiments show that neuron-specific loss of HIF-1 increases ischemic brain injury, and the recovery of neural function in ischemic rats is related to the increased expression of hypoxia-inducible factor subtype 1α (HIF-1α). [10,11] And more recently, anesthetics and perioperative drugs have been reported to affect HIF-1 activity. [16][17][18][19][20] Research reports that the anesthetics inhibit HIF-1 activation and downstream gene expression.…”