Dynamic arterial blood gas analysis in conscious, unrestrained C57BL/6J mice during exposure to intermittent hypoxia

Abstract

Rodent models of chronic intermittent hypoxia (IH) are commonly used to investigate the pathophysiological sequelae that result from hypoxic exposure in patients experiencing obstructive sleep apnea (OSA). Despite the widespread use of IH models, little attention has been paid to carefully defining the degree of oxyhemoglobin desaturation that occurs during each hypoxic period. Therefore, we developed a rapid blood sampling technique to determine the arterial blood gas changes that occur in conscious unrestrained mice during a single IH event and hypothesized that the arterial Po(2) (Pa(O(2))) at the nadir level of the inspired oxygen profile causes oxyhemoglobin saturation to fall to between 80% and 90%. Mice were exposed to 120-180 cycles of IH at a rate of 60 cycles/h, and arterial blood samples were withdrawn (<3 s) at baseline and at 10-s time intervals over the course of a single IH cycle. The IH regimen caused a decline in the fraction of inspired oxygen from room air levels to a transient nadir of 6.0 +/- 0.2% over the 30-s hypoxic period. The Pa(O(2)) and arterial oxyhemoglobin saturation reached a nadir of 47 +/- 2 mmHg and 85 +/- 2% at 30 s, respectively. Arterial Pco(2) decreased to a nadir of 26 +/- 2 mmHg at 30 s, associated with a rise in arterial pH to 7.46 +/- 0.2. We conclude that the magnitude of oxyhemoglobin desaturation that is induced in our murine model of IH is consistent with the degree of hypoxic stress that occurs in moderate to severe clinical OSA.

Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea

“…1). This pattern of O 2 concentration in the air breathed by the animals was very close to the ones used in a recent study measuring arterial oxygen saturation (SaO 2 ) in free-moving mice [27]. Accordingly, the arterial oxygen desaturation pattern of the mice in the present study was expected to range between 100% and 85% [27].…”

“…This pattern of O 2 concentration in the air breathed by the animals was very close to the ones used in a recent study measuring arterial oxygen saturation (SaO 2 ) in free-moving mice [27]. Accordingly, the arterial oxygen desaturation pattern of the mice in the present study was expected to range between 100% and 85% [27]. To minimize any potential effect of social stress on tumor progression [28], each group of mice was kept together in a cage, both during the application of intermittent hypoxia and throughout the rest of the day.…”

Sleep Apnea Research in Animals. Past, Present, and Future

“…A common technique lowers the ambient cage oxygen to 5%, 60 times/h, resulting in a mouse arterial oxygen saturation nadir ranging from less than 50% (45) to 67% (33). Lee and colleagues measured arterial blood gases during this type of IH at 10-second intervals and reported a milder nadir of 85%, perhaps related to averaging between sampling intervals (46). Using an electrode to probe tissue oxygen levels in anesthetized mice, Reinke and colleagues (45) noted that IH induced large amplitude fluctuations in liver oxygen, with attenuated or nearly absent fluctuations in muscle and adipose tissue, respectively (Figure 4).…”

Adipose Tissue in Sleep Apnea

“…In mice and rats, exposure to intermittent hypoxia during the daytime (sleep period for rodents) has been extensively used to reproduce the oscillations in arterial oxygen saturation (SaO 2 ) seen in OSA patients during sleep (Jun & Polotsky, 2009;Lee, Woodske, Zou, & O'Donnell, 2009). Another model used upper airway closure to cause OSA in anesthetized rats (Farré et al, 2007).…”