The ability of fishes, amphibians, and reptiles to survive extremes of oxygen availability derives from a core triad of adaptations: profound metabolic suppression, tolerance of ionic and pH disturbances, and mechanisms for avoiding free-radical injury during reoxygenation. For long-term anoxic survival, enhanced storage of glycogen in critical tissues is also necessary. The diversity of body morphologies and habitats and the utilization of dormancy have resulted in a broad array of adaptations to hypoxia in lower vertebrates. For example, the most anoxia-tolerant vertebrates, painted turtles and crucian carp, meet the challenge of variable oxygen in fundamentally different ways: Turtles undergo near-suspended animation, whereas carp remain active and responsive in the absence of oxygen. Although the mechanisms of survival in both of these cases include large stores of glycogen and drastically decreased metabolism, other mechanisms, such as regulation of ion channels in excitable membranes, are apparently divergent. Common themes in the regulatory adjustments to hypoxia involve control of metabolism and ion channel conductance by protein phosphorylation. Tolerance of decreased energy charge and accumulating anaerobic end products as well as enhanced antioxidant defenses and regenerative capacities are also key to hypoxia survival in lower vertebrates.

Multivariate analysis indicated that Sao2 level, sensor type, skin color, and gender were predictive of errors in Spo2 estimates at low Sao2 levels. The data suggest that clinically important bias should be considered when monitoring patients with saturations below 80%, especially those with darkly pigmented skin; but further study is needed to confirm these observations in the relevant populations.

The three tested pulse oximeters overestimated arterial oxygen saturation during hypoxia in dark-skinned individuals.

Snakebite remains a neglected medical problem of the developing world with up to 125,000 deaths each year despite more than a century of calls to improve snakebite prevention and care. An estimated 75% of fatalities from snakebite occur outside the hospital setting. Because phospholipase A2 (PLA2) activity is an important component of venom toxicity, we sought candidate PLA2 inhibitors by directly testing drugs. Surprisingly, varespladib and its orally bioavailable prodrug, methyl-varespladib showed high-level secretory PLA2 (sPLA2) inhibition at nanomolar and picomolar concentrations against 28 medically important snake venoms from six continents. In vivo proof-of-concept studies with varespladib had striking survival benefit against lethal doses of Micrurus fulvius and Vipera berus venom, and suppressed venom-induced sPLA2 activity in rats challenged with 100% lethal doses of M. fulvius venom. Rapid development and deployment of a broad-spectrum PLA2 inhibitor alone or in combination with other small molecule inhibitors of snake toxins (e.g., metalloproteases) could fill the critical therapeutic gap spanning pre-referral and hospital setting. Lower barriers for clinical testing of safety tested, repurposed small molecule therapeutics are a potentially economical and effective path forward to fill the pre-referral gap in the setting of snakebite.

While responsive to desaturation, cerebral oximeters exhibited large variation in reading errors between subjects, with mean bias possibly related to variations in the ratio of arterial and venous blood in the sampling area of the brain. This ratio is probably not fixed, as assumed by the manufacturers, but dynamically changes with hypoxia. Better understanding these factors could improve the performance of cerebral oximeters and help establish saturation or blood flow thresholds for brain well-being.