Acute normobaric hypoxia does not increase blood or plasma viscosity

1 Introduction

Chronic hypoxia, and the resulting polycythemia, is known to increase blood viscosity [1, 2]. Likewise, maximal exercise, which is known to result in hemoconcentration and acute hypoxemia in about half of endurance athletes, also increases blood viscosity [3, 4]. In both these scenarios, however, the increase in hematocrit may have confounded how to interpretation the effect hypoxemia has on blood viscosity [5–7]. Considering the above, the purpose of the current study was to determine the effect of acute hypoxia on blood and plasma viscosity independent of alterations in Hct. This was accomplished using acute normobaric hypoxia (inspired oxygen = 15%), which typically causes hemoglobin oxygen saturation to decrease from 98% to approximately 85% during seated rest [8].

2 Methods

The subjects for this study were nine healthy volunteers (five males and four females all non-smokers) with a mean±SD age of 28±4 years. The study was approved by the SDSU IRB and signed informed consent was obtained prior to the start of data collection. Subjects reported to the laboratory eight hours post-prandial and after having refrained from exercise for at least ten hours. The subjects breathed room air for 30 min while sitting in a chair, after which blood was collected via venipuncture into EDTA treated vacutainers. Hemoglobin oxygen saturation was measured every five minutes on the left index finger using a Nonin pulse oximeter (model 8500). While remaining seated, the subjects next breathed 15% oxygen for 30 minutes from an inflated 100 liter Douglas bag via a one-way valve. The bag was filled with 15% oxygen using an oxygen scrubber (Higher Peak, Boston MA) and was continually monitored for oxygen concentration using a portable oxygen analyzer (Oxycheq, Marianna, FL). The inspired oxygen concentration for all experiments ranged between 14.8 and 15.2%. Hemoglobin oxygen saturation was again measured every five min using a pulse oximeter. At the end of the 30 min seated exposure to 15% oxygen, a second blood sample was collected as previously described. The treatment order was normoxia for the first 30 min followed by 30 min of hypoxia for all subjects to eliminate any potential residual effect that hypoxia might have had on blood viscosity. Pilot data revealed that 30 min of normoxia had no effect on blood viscosity during the subsequent 30 min time period.

Both the normoxic and hypoxic blood samples were measured for hematocrit, blood viscosity, and plasma viscosity. To keep the blood samples from being exposed to ambient air, a blunt tip needle was inserted into the vacutainer cap and approximately 3 ml of blood was aspirated by hand into a syringe. The tip of the needle was then removed from the vacutainer and immediately inserted into a blind-ended glass tube that had an internal diameter equal to the external diameter of the needle. Blood was then expressed by hand into the glass tube from the blind end until it was completely filled at which time a stainless steel ball was added; after which it was immediately capped. Blood viscosity was measured using a rolling ball viscometer (Anton–Parr, model 2000). Shear rates greater than 200 s^–1 were used for all blood and plasma viscosity measurements. The remainder of the blood in the syringe was then used to fill two microcapillary tubes which were spun in a microhematocrit centrifuge for five min and read to determine Hct. The vacutainer was then centrifuged at 4 °C for 15 min at 2500 rpm to obtain a plasma sample which was extracted as previously described. Plasma viscosity was measured using the same viscometer. Blood and plasma viscosity were measured within 30 min of collection.

Paired t tests were used to compare normoxic vs. hypoxic data. The alpha level was set a P < 0.05 and each comparison was corrected using the Bonferroni procedure.

3 Results

The mean±SD hemoglobin oxygen saturation significantly (P < 0.05) decreased from 98±1% during normoxia to 87±2% during hypoxia. The magnitude of the decrease is consistent with past findings [8]. Hematocrit was essentially identical for the two conditions (42.1±1.6% vs. 42.0±1.7%). Blood viscosity was not significantly different for the two conditions with a mean of 2.89±0.17 cP during normoxia and 2.83±0.19 cP during hypoxia. Likewise, plasma viscosity was not significantly different for the two conditions with a mean of 1.19±0.04 cP during normoxia and 1.19±0.05 cP during hypoxia.

4 Discussion

Chronic hypoxia from altitude exposure is well known to increase blood viscosity [1, 2]. Most of the increase is believed to be the result of the profound polycythemia that occurs with altitude acclimation. For example, Stauffer et al. [1] have reported that blood viscosity at a shear rate of 45 s^–1 is significantly increased 3-fold in highland residents living at 5,100 m compared to lowlanders at sea level. Hematocrit was also significantly different (65 vs. 42%, respectively) in the two groups. Interestingly, at 5,100 m, highland residents with moderate to severe chronic mountain sickness, who displayed significant hypoxemia, had a higher blood viscosity compared to highlanders without chronic mountain sickness, even at a corrected hematocrit (40%). Such results suggest that increased blood viscosity is involved in chronic mountain sickness pathophysiology.

Maximal exercise, which is known to cause exercise induced hypoxemia in approximately half of endurance athletes, has also been shown to increase blood viscosity and hematocrit [3, 4]. In this case the increased hematocrit is the result of hemoconcentration from increased plasma fluid loss via changes in hydrostatic pressure. Previous studies suggest that increases in blood viscosity during exercise may promote hypoxemia via stress failure at the pulmonary capillary level [4, 9].

The current study found no change in blood or plasma viscosity after 30 min of breathing 15% oxygen, which significantly decreased the mean arterial hemoglobin oxygen saturation from 98 to 87%. To our knowledge this is the first study to examine the effect of acute normobaric hypoxia on blood and plasma viscosity in humans. Such results are an important addition to the scientific literature, as comparing the effect of hypoxemia from either chronic altitude exposure or maximal exercise in endurance-trained athletes to acute, normobaric hypoxia- which was used in the current study- is difficult as different physiological adaptations and mechanisms are involved.

Our data are consistent with past studies that have examined the effect of acute hypoxia on blood viscosity/RBC deformability. For example, Usami et al. [10] reported that decreasing the PO₂ to as low as 4 mmHg had no effect on blood viscosity at both high (208 s^–1) and low (0.052 s^–1) shear rates. Likewise, Doyle and Walker [11] reported that acute hypoxia (3% O₂) had no effect on rat RBC deformability as measured by microcapillary filtration compared to normoxia (21% O₂). Lastly, Moon et al. [12] have recently shown that RBC deformability was unchanged in resting human subjects breathing air with 11.2% oxygen vs. normoxia, even though the arterial hemoglobin saturation was reduced to 78% during hypoxia.

In conclusion, the results of the current study suggest that acute normobaric hypoxia, independent of changes in hematocrit, does not increase blood or plasma viscosity.