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Updated: Jul 9, 2026

Delivery of In Vivo Acute Intermittent Hypoxia in Neonatal Rodents to Prime Subventricular Zone-derived Neural Progenitor Cell Cultures
Published on: November 2, 2015
The effect of two different intermittent hypoxia protocols on ventilatory responses to hypoxia and carbon dioxide at
Michael Koehle1, William Sheel, William Milsom
1University of British Columbia, Faculty of Medicine. michael.koehle@gmail.com
Unlabelled:
Intermittent hypoxia (IH) consists of bouts of hypoxic exposure interspersed with normoxic intervals. The optimal IH regime for increasing the ventilatory response in humans is unknown, although in animals there is evidence that multiple short duration bouts of intermittent hypoxia (SDIH) provoke larger changes in chemosensitivity than longer duration bouts of intermittent hypoxia (LDIH). The purpose of this study was to compare responses to both hypercapnia and hypoxia between the two protocols.
Methods:
In a randomised crossover design, 10 healthy males underwent two 7-day poikilocapnic IH protocols. The LDIH protocol consisted of daily 60-minute exposures to normobaric 12% O2 (balance N2). The SDIH protocol comprised twelve 5-minute bouts of normobaric 12% O2, separated by 5-minute bouts of room air daily. We measured the isocapnic acute hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR) and CO2 threshold and sensitivity by the modified Read rebreathing technique. Pre-testing was performed immediately prior to intermittent hypoxic training. Follow-up testing occurred on the first day following IH and at 7 days after completion of IH. HVR testing was also performed on every day of the IH protocol prior to the hypoxic exposure.
Results:
Following each 7-day IH protocol, mean HVR was significantly (p < 0.05) increased by 67% and 49% (for LDIH and SDIH, respectively). One week post IH, HVR values were not different from pre-values. HCVR was increased significantly by the LDIH protocol by 44.1% (p < 0.01) and remained elevated by 41.5% at 7 days post (p < 0.01). The changes following the SDIH protocol were smaller (20.7% and 13.5%, at 1 and 7 days post IH, respectively) and not significant. The HCVR remained elevated 7 days following IH (26.7%, p < 0.01). In both the hyperoxic and hypoxic modified rebreathing tests, the CO2 sensitivity was unchanged by either intervention. In hypoxia, the CO2 threshold was significantly reduced following both protocols (p < 0.05). LDIH reduced the threshold by 1.60mmHg, whereas following SDIH it was reduced by 1.98mmHg. Under hyperoxic conditions, LDIH reduced the CO2 threshold by 2.06 mmHg, and SDIH caused a reduction of 2.53 mmHg. There were no significant differences between the two IH protocols for any of the above measures. A 7-day intermittent hypoxic protocol consisting of daily 60-minute exposures to normobaric poikilocapnic hypoxia caused increases in HVR and HCVR. This protocol caused a left-shift in the CO2 threshold but no change in CO2 sensitivity by the modified rebreathing protocol. Neither protocol proved superior in effecting these changes in the resting control of breathing.
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