Minocycline prevents the attenuated acute hypoxic ventilatory response and changes in brainstem neurochemistry following neonatal sustained hypoxia exposure (1092.11)

Acclimatization to altitude involves an increase in the acute hypoxic ventilatory response (AHVR). Because low-dose dopamine decreases AHVR and domperidone increases AHVR, the increase in AHVR at altitude may be generated by a decrease in peripheral dopaminergic activity. The AHVR of nine subjects was determined with and without a prior period of 8 h of isocapnic hypoxia under each of three pharmacological conditions: 1) control, with no drug administered; 2) dopamine (3 μg ⋅ min−1 ⋅ kg−1); and 3) domperidone (Motilin, 40 mg). AHVR increased after hypoxia ( P ≤ 0.001). Dopamine decreased ( P ≤ 0.01), and domperidone increased ( P ≤ 0.005) AHVR. The effect of both drugs on AHVR appeared larger after hypoxia, an observation supported by a significant interaction between prior hypoxia and drug in the analysis of variance ( P ≤ 0.05). Although the increased effect of domperidone after hypoxia of 0.40 l ⋅ min−1 ⋅ %saturation−1[95% confidence interval (CI) −0.11 to 0.92 l ⋅ min−1 ⋅ %−1] did not reach significance, the lower limit for this confidence interval suggests that little of the increase in AHVR after sustained hypoxia was brought about by a decrease in peripheral dopaminergic inhibition.

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Effects of A 2 a Receptors on the Hypoxic Ventilatory Response in Rats Exposed to Chronic Sustained Hypoxia

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.659.2 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

K Basaran ◽

Esteban Moya ◽

Zengxing Fu ◽

Frank Powell

Keyword(s):

Ventilatory Response ◽

Hypoxic Ventilatory Response ◽

Sustained Hypoxia

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Role of endogenous adenosine in hypoxic ventilatory response in humans: a study with dipyridamole

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.1.196 ◽

1994 ◽

Vol 76 (1) ◽

pp. 196-203 ◽

Cited By ~ 20

Author(s):

M. Yamamoto ◽

M. Nishimura ◽

S. Kobayashi ◽

Y. Akiyama ◽

K. Miyamoto ◽

...

Keyword(s):

Ventilatory Response ◽

Minute Ventilation ◽

Crossover Fashion ◽

Hypoxic Ventilatory Response ◽

Double Blind ◽

Adenosine Receptor Antagonist ◽

Endogenous Adenosine ◽

Progressive Hypoxia ◽

Sustained Hypoxia

To examine the role of endogenous adenosine in hypoxic ventilatory response, we measured, in nine normal young adults, ventilatory responses to isocapnic progressive hypoxia and subsequent sustained hypoxia [arterial O2 saturation (SaO2); 80%, 20 min] with and without pretreatment with dipyridamole in a double-blind crossover fashion. Dipyridamole, an adenosine uptake blocker, was expected to enhance the effect of endogenous adenosine. Pretreatment with dipyridamole (0.5 mg/kg) significantly augmented the slope of the ventilatory response to isocapnic progressive hypoxia from 0.35 +/- 0.13 (SE) to 0.70 +/- 0.25 l.min-1.%fall of SaO2(-1) (P < 0.01), although there were no significant changes in resting ventilation. On the other hand, minute ventilation, when expressed as a percentage of peak ventilation, declined to 68.4 +/- 4.3% with dipyridamole at the 9–11th min of sustained hypoxia, which was significantly lower than the 90.2 +/- 8.3% with a placebo (P < 0.05), and finally reached 56.1 +/- 7.2% with dipyridamole and 78.7 +/- 9.2% with the placebo (P < 0.1) at the 18–20th min of sustained hypoxia. In an attempt to more specifically examine the role of adenosine, aminophylline (5 mg/kg), an adenosine receptor antagonist, was injected before pretreatment with dipyridamole in four subjects. Aminophylline infusion abolished or at least attenuated the effect of dipyridamole in all four subjects. These data suggest that endogenous adenosine has a modulatory role in hypoxic ventilatory response in adult humans.

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Prior Exposure To Sustained Hypoxia Impairs The Acute Hypoxic Ventilatory Response In Rat Pups Following Postnatal Chronic Intermittent Hypoxia

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.1090.10 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Peter MacFarlane ◽

Jingning Ao ◽

Catherine Mayer ◽

Juliann Di Fiore ◽

Christopher Wilson ◽

...

Keyword(s):

Intermittent Hypoxia ◽

Ventilatory Response ◽

Prior Exposure ◽

Chronic Intermittent Hypoxia ◽

Hypoxic Ventilatory Response ◽

Rat Pups ◽

Sustained Hypoxia

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Effect of brain blood flow on hypoxic ventilatory response in humans

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.3.1100 ◽

1987 ◽

Vol 63 (3) ◽

pp. 1100-1106 ◽

Cited By ~ 16

Author(s):

M. Nishimura ◽

A. Suzuki ◽

Y. Nishiura ◽

H. Yamamoto ◽

K. Miyamoto ◽

...

Keyword(s):

Blood Flow ◽

Ventilatory Response ◽

Minute Ventilation ◽

Venous Blood ◽

Blood Gases ◽

Interindividual Variation ◽

Brain Blood Flow ◽

Hypoxic Ventilatory Response ◽

Arterial O2 Saturation ◽

Sustained Hypoxia

To assess the effect of brain blood flow on hypoxic ventilatory response, we measured arterial and internal jugular venous blood gases and ventilation simultaneously and repeatedly in eight healthy male humans in two settings: 1) progressive and subsequent sustained hypoxia, and 2) stepwise and progressive hypercapnia. Ventilatory response to progressive isocapnic hypoxia [arterial O2 partial pressure 155.9 +/- 4.0 (SE) to 46.7 +/- 1.5 Torr] was expressed as change in minute ventilation per change in arterial O2 saturation and varied from -0.16 to -1.88 [0.67 +/- 0.19 (SE)] l/min per % among subjects. In the meanwhile, jugular venous PCO2 (PjCO2) decreased significantly from 51.0 +/- 1.1 to 47.3 +/- 1.0 Torr (P less than 0.01), probably due to the increase in brain blood flow, and stayed at the same level during 15 min of sustained hypoxia. Based on the assumption that PjCO2 reflects the brain tissue PCO2, we evaluated the depressant effect of fall in PjCO2 on hypoxic ventilatory response, using a slope for ventilation-PjCO2 line which was determined in the second set of experiments. Hypoxic ventilatory response corrected with this factor was -1.31 +/- 0.33 l/min per %, indicating that this factor modulated hypoxic ventilatory response in humans. The ventilatory response to progressive isocapnic hypoxia did not correlate with this factor but significantly correlated with the withdrawal test (modified transient O2 test), which was performed on a separate day. Accordingly we conclude that an increase in brain blood flow during exposure to moderate hypoxia may substantially attenuate the ventilatory response but that it is unlikely to be the major factor of the interindividual variation of progressive isocapnic hypoxic ventilatory response in humans.

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Recovery of the ventilatory response to hypoxia in normal adults

Journal of Applied Physiology ◽

10.1152/jappl.1988.64.2.521 ◽

1988 ◽

Vol 64 (2) ◽

pp. 521-528 ◽

Cited By ~ 61

Author(s):

P. A. Easton ◽

L. J. Slykerman ◽

N. R. Anthonisen

Keyword(s):

Young Adults ◽

Ventilatory Response ◽

Hypoxic Exposure ◽

Hypoxic Ventilatory Response ◽

Air Breathing ◽

Arterial Blood ◽

Complete Reversal ◽

Sustained Hypoxia ◽

Normal Adults ◽

Ventilatory Response To Hypoxia

Recovery of the initial ventilatory response to hypoxia was examined after the ventilatory response had declined during sustained hypoxia. Normal young adults were exposed to two consecutive 25-min periods of sustained isocapnic hypoxia (80% O2 saturation in arterial blood), separated by varying interludes of room air breathing or an increased inspired O2 fraction (FIO2). The decline in the hypoxic ventilatory response during the 1st 25 min of hypoxia was not restored after a 7-min interlude of room air breathing; inspired ventilation (VI) at the end of the first hypoxic period was not different from VI at the beginning and end of the second hypoxic period. After a 15-min interlude of room air breathing, the hypoxic ventilatory response had begun to recover. With a 60-min interlude of room air breathing, recovery was complete; VI during the second hypoxic exposure matched VI during the first hypoxic period. Ventilatory recovery was accelerated by breathing supplemental O2. With a 15-min interlude of 0.3 FIO2 or 7 min of 1.0 FIO2, VI of the first and second hypoxic periods were equivalent. Both the decline and recovery of the hypoxic ventilatory response were related to alterations in tidal volume and mean inspiratory flow (VT/TI), with little alteration in respiratory timing. We conclude that the mechanism of the decline in the ventilatory response with sustained hypoxia may require up to 1 h for complete reversal and that the restoration is O2 sensitive.

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