CORP: Sources and degrees of variability in whole animal intermittent hypoxia experiments.

Chamber exposures are commonly used to evaluate the physiological and pathophysiological consequences of intermittent hypoxia in animal models. Researchers in this field use both commercial and custom-built chambers in their experiments. The purpose of this Cores of Reproducibility in Physiology paper is to demonstrate potential sources of variability in these systems that researchers should consider. Evaluating the relationship between arterial oxygen saturation and inspired oxygen concentration, we found that there are important sex-dependent differences in the commonly used C57BL6/J mouse model. The time delay of the oxygen sensor that provides feedback to the system during the ramp-down and ramp-up phases was different, limiting the number of cycles per hour that can be conducted and the overall stability of the oxygen concentration. The time to reach the hypoxic and normoxic hold stages, and the overall oxygen concentration, were impacted by the cycle number. These variables were further impacted by whether there are animals present in the chamber, highlighting the importance of verifying the cycling frequency with animals in the chamber. At ≤14 cycles/h, instability in the chamber oxygen concentration did not impact arterial oxygen saturation but may be important at higher cycle numbers. Taken together, these data demonstrate the important sources of variability that justify reporting and verifying the target oxygen concentration, cycling frequency, and arterial oxygen concentration, particularly when comparing different animal models and chamber configurations.NEW & NOTEWORTHY Intermittent hypoxia exposures are commonly used in physiology and many investigators use chamber systems to perform these studies. Because of the variety of chamber systems and protocols used, it is important to understand the sources of variability in intermittent hypoxia experiments that can impact reproducibility. We demonstrate sources of variability that come from the animal model, the intermittent hypoxia protocol, and the chamber system that can impact reproducibility.

Case Studies in Physiology: Untangling the cause of hypoxemia in a patient with obesity with acute leukemia.

Diagnosing the cause of hypoxemia and dyspnea can be complicated in complex patients with multiple comorbidities. This "Case Study in Physiology" describes an man with obesity admitted to the hospital for relapse of acute lymphoblastic leukemia, who experienced progressive hypoxemia, shortness of breath, and dyspnea on exertion during his hospitalization. After initial empirical treatment with diuresis and antibiotics failed to improve his symptoms and because an arterial blood gas measurement was not readily available, we applied a novel, recently described physiological method to estimate the arterial partial pressure of oxygen from the peripheral saturation measurement and calculate the alveolar-arterial oxygen difference to discern the source of his hypoxemia and dyspnea. Using basic physiological principles, we describe how hypoventilation, anemia, and the use of a ß blocker and furosemide, collaborated to create a "perfect storm" in this patient that impaired oxygen delivery and limited utilization. This case illustrates the application of innovative physiology methodology in medicine and provides a strong rationale for continuing to integrate physiology education in medical education.NEW & NOTEWORTHY Discerning the cause of dyspnea and hypoxemia in complex patients can be difficult. We describe the "real world" application of an innovative methodology to untangle the underlying physiology in a patient with multiple comorbidities. This case further demonstrates the importance of applying physiology to interrogate the underlying cause of a patient's symptoms when treatment based on probability fails.