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The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with Presbyterian hemoglobinopathy

The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with... The purpose of this study was to test whether chronically enhanced O 2 delivery to tissues, without arterial hyperoxia, can change acute ventilatory responses to hypercapnia and hypoxia. The effects of decreased hemoglobin (Hb)-O 2 affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% CO 2 in O 2 ) and hypoxia (10 and 15% O 2 in N 2 ) were assessed in mutant mice expressing Hb Presbyterian (mutation in the -globin gene, 108 Asn → Lys). O 2 consumption during normoxia, measured via open-circuit methods, was significantly higher in the mutant mice than in wild-type mice. Respiratory measurements were conducted with a whole body, unrestrained, single-chamber plethysmograph under conscious conditions. During hypercapnia, there was no difference between the slopes of the hypercapnic ventilatory responses, whereas minute ventilation at the same levels of arterial P CO 2 was lower in the Presbyterian mice than in the wild-type mice. During both hypoxic exposures, ventilatory responses were blunted in the mutant mice compared with responses in the wild-type mice. The effects of brief hyperoxia exposure (100% O 2 ) after 10% hypoxia on ventilation were examined in anesthetized, spontaneously breathing mice with a double-chamber plethysmograph. No significant difference was found in ventilatory responses to brief hypoxia between both groups of mice, indicating possible involvement of central mechanisms in blunted ventilatory responses to hypoxia in Presbyterian mice. We conclude that chronically enhanced O 2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures. hyperoxia; hypoxia; hypercapnia; tissue; breathing Address for reprint requests and other correspondence: I. Homma, Dept. of Physiology, Showa Univ. School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan (E-mail: ihomma@med.showa-u.ac.jp ). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Regulatory, Integrative and Comparative Physiology The American Physiological Society

The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with Presbyterian hemoglobinopathy

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References (25)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6119
eISSN
1522-1490
DOI
10.1152/ajpregu.00104.2003
pmid
12829441
Publisher site
See Article on Publisher Site

Abstract

The purpose of this study was to test whether chronically enhanced O 2 delivery to tissues, without arterial hyperoxia, can change acute ventilatory responses to hypercapnia and hypoxia. The effects of decreased hemoglobin (Hb)-O 2 affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% CO 2 in O 2 ) and hypoxia (10 and 15% O 2 in N 2 ) were assessed in mutant mice expressing Hb Presbyterian (mutation in the -globin gene, 108 Asn → Lys). O 2 consumption during normoxia, measured via open-circuit methods, was significantly higher in the mutant mice than in wild-type mice. Respiratory measurements were conducted with a whole body, unrestrained, single-chamber plethysmograph under conscious conditions. During hypercapnia, there was no difference between the slopes of the hypercapnic ventilatory responses, whereas minute ventilation at the same levels of arterial P CO 2 was lower in the Presbyterian mice than in the wild-type mice. During both hypoxic exposures, ventilatory responses were blunted in the mutant mice compared with responses in the wild-type mice. The effects of brief hyperoxia exposure (100% O 2 ) after 10% hypoxia on ventilation were examined in anesthetized, spontaneously breathing mice with a double-chamber plethysmograph. No significant difference was found in ventilatory responses to brief hypoxia between both groups of mice, indicating possible involvement of central mechanisms in blunted ventilatory responses to hypoxia in Presbyterian mice. We conclude that chronically enhanced O 2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures. hyperoxia; hypoxia; hypercapnia; tissue; breathing Address for reprint requests and other correspondence: I. Homma, Dept. of Physiology, Showa Univ. School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan (E-mail: ihomma@med.showa-u.ac.jp ).

Journal

AJP - Regulatory, Integrative and Comparative PhysiologyThe American Physiological Society

Published: Oct 1, 2003

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