Mitochondrial Oxygenation During Cardiopulmonary Bypass: A Pilot Study

Oxygen (O(2)) is an essential nutrient that serves as a key substrate in cellular metabolism and bioenergetics. In a variety of physiological and pathological states, organisms encounter insufficient O(2) availability, or hypoxia. In order to cope with this stress, evolutionarily conserved responses are engaged. In mammals, the primary transcriptional response to hypoxic stress is mediated by the hypoxia-inducible factors (HIFs). While canonically regulated by prolyl hydroxylase domain-containing enzymes (PHDs), the HIFα subunits are intricately responsive to numerous other factors, including factor-inhibiting HIF1α (FIH1), sirtuins, and metabolites. These transcription factors function in normal tissue homeostasis and impinge on critical aspects of disease progression and recovery. Insights from basic HIF biology are being translated into pharmaceuticals targeting the HIF pathway. Copyright © 2010 Elsevier Inc. All rights reserved.

Continuous real-time monitoring of the adequacy of cerebral perfusion can provide important therapeutic information in a variety of clinical settings. The current clinical availability of several non-invasive near-infrared spectroscopy (NIRS)-based cerebral oximetry devices represents a potentially important development for the detection of cerebral ischaemia. In addition, a number of preliminary studies have reported on the application of cerebral oximetry sensors to other tissue beds including splanchnic, renal, and spinal cord. This review provides a synopsis of the mode of operation, current limitations and confounders, clinical applications, and potential future uses of such NIRS devices.

The extensive oxygen gradient between the air we breathe (Po2 ~21 kPa) and its ultimate distribution within mitochondria (as low as ~0.5-1 kPa) is testament to the efforts expended in limiting its inherent toxicity. It has long been recognized that cell culture undertaken under room air conditions falls short of replicating this protection in vitro. Despite this, difficulty in accurately determining the appropriate O2 levels in which to culture cells, coupled with a lack of the technology to replicate and maintain a physiological O2 environment in vitro, has hindered addressing this issue thus far. In this review, we aim to address the current understanding of tissue Po2 distribution in vivo and summarize the attempts made to replicate these conditions in vitro. The state-of-the-art techniques employed to accurately determine O2 levels, as well as the issues associated with reproducing physiological O2 levels in vitro, are also critically reviewed. We aim to provide the framework for researchers to undertake cell culture under O2 levels relevant to specific tissues and organs. We envisage that this review will facilitate a paradigm shift, enabling translation of findings under physiological conditions in vitro to disease pathology and the design of novel therapeutics.