Published ahead of print on March 5, 2003, doi:10.1164/rccm.200208-963OC
Am. J. Respir. Crit. Care Med., Volume 167, Number 11, June 2003, 1540-1547
A more recent version of this article appeared on June 1, 2003
Submitted on September 3, 2002
Accepted on March 1, 2003
Respiratory Effects of Gestational Intermittent Hypoxia in the Developing Rat
David Gozal1*, Stephen R Reeves1, Barry W Row2, Jennifer J Neville2, Shang Z Guo2, and Andrew J Lipton2
1 Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Louisville, KY, USA; Pharmacology and Toxicology, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Louisville, KY, USA,
2 Pediatrics, Kosair Children's Hospital Research Institute, University of Louisville School of Medicine, Louisville, KY, USA
* To whom correspondence should be addressed. E-mail: david.gozal{at}louisville.edu.
Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea, occurs frequently during pregnancy. We hypothesized that IH leads to persistent post-natal changes in respiratory responses to acute hypoxia and adverse effects on spatial function. Time-pregnant Sprague Dawley rats were exposed to IH (IHRA; 21% and 10% O2 alternations every 90 sec) or to normoxia (RARA) until delivery. Ventilatory and metabolic responses to a 20-min acute hypoxic challenge (10% O2) were conducted at post-natal ages 5-30 days. In addition, spatial task learning was assessed in the Morris water maze at 1 and 4 months. Normoxic ventilation was higher at all time points in IHRA rats (p<0.01). Peak hypoxic ventilatory responses (pHVR) were attenuated in IHRA at 5-days of age and hypoxic ventilatory depression (HVD) was accentuated at this age. However, ventilatory equivalents (minute ventilation/oxygen consumption) revealed significant reductions in IHRA at pHVR and HVD at all post-natal ages (p<0.01). Acquisition and retention of a spatial task were similar in the 2 groups at both 1 and 4 months of age. We conclude that gestational intermittent hypoxia elicits long-lasting alterations in respiratory control. We postulate that such IH-induced respiratory plasticity may create selective vulnerability to hypoxia during development.
Key words: sleep, intermittent hypoxia, obstructive sleep apnea, cognitive impairment, memory, water maze, hypoxic ventilatory response
This article has been cited by other articles:
|
|
|
|
 
G. K. Soukhova-O'Hare, Z. A. Shah, Z. Lei, A. D. Nozdrachev, C. V. Rao, and D. Gozal
Erectile Dysfunction in a Murine Model of Sleep Apnea
Am. J. Respir. Crit. Care Med.,
September 15, 2008;
178(6):
644 - 650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Soukhova-O'Hare, R. V. Ortines, Y. Gu, A. D. Nozdrachev, S. D. Prabhu, and D. Gozal
Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats: The Role of Reactive Oxygen Species and L-Ca2+ Channels
Hypertension,
July 1, 2008;
52(1):
156 - 162.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Bavis and G. S. Mitchell
Long-term effects of the perinatal environment on respiratory control
J Appl Physiol,
April 1, 2008;
104(4):
1220 - 1229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dubois, H. Houchi, M. Naassila, M. Daoust, and O. Pierrefiche
Blunted response to low oxygen of rat respiratory network after perinatal ethanol exposure: involvement of inhibitory control
J. Physiol.,
March 1, 2008;
586(5):
1413 - 1427.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Mahamed and G. S. Mitchell
Sleep Apnoea & Hypertension: Physiological bases for a causal relation: Is there a link between intermittent hypoxia-induced respiratory plasticity and obstructive sleep apnoea?
Exp Physiol,
January 1, 2007;
92(1):
27 - 37.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Reeves, G. S. Mitchell, and D. Gozal
Early postnatal chronic intermittent hypoxia modifies hypoxic respiratory responses and long-term phrenic facilitation in adult rats
Am J Physiol Regulatory Integrative Comp Physiol,
June 1, 2006;
290(6):
R1664 - R1671.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Soukhova-O'Hare, Z. Cheng, A. M. Roberts, and D. Gozal
Postnatal intermittent hypoxia alters baroreflex function in adult rats
Am J Physiol Heart Circ Physiol,
March 1, 2006;
290(3):
H1157 - H1164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Greer, G. D. Funk, and K. Ballanyi
Preparing for the first breath: prenatal maturation of respiratory neural control
J. Physiol.,
February 1, 2006;
570(3):
437 - 444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Zhan, F. Serrano, P. Fenik, R. Hsu, L. Kong, D. Pratico, E. Klann, and S. C. Veasey
NADPH Oxidase Mediates Hypersomnolence and Brain Oxidative Injury in a Murine Model of Sleep Apnea
Am. J. Respir. Crit. Care Med.,
October 1, 2005;
172(7):
921 - 929.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Zhan, P. Fenik, D. Pratico, and S. C. Veasey
Inducible Nitric Oxide Synthase in Long-term Intermittent Hypoxia: Hypersomnolence and Brain Injury
Am. J. Respir. Crit. Care Med.,
June 15, 2005;
171(12):
1414 - 1420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. McGuire and L. Ling
Ventilatory long-term facilitation is greater in 1- vs. 2-mo-old awake rats
J Appl Physiol,
April 1, 2005;
98(4):
1195 - 1201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Sleep-Disordered Breathing, Control of Breathing, Respiratory Muscles, Pulmonary Function Testing in AJRCCM 2003
Am. J. Respir. Crit. Care Med.,
January 15, 2004;
169(2):
254 - 264.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Tobin
Pediatrics, Surfactant, and Cystic Fibrosis in AJRCCM 2003
Am. J. Respir. Crit. Care Med.,
January 15, 2004;
169(2):
277 - 287.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. S Cherniack
Oxygen sensing: applications in humans
J Appl Physiol,
January 1, 2004;
96(1):
352 - 358.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2003 American Thoracic Society
|
|
|
