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

Masahiko Izumizaki, Masakatsu Tamaki, Yo Ichi Suzuki, Michiko Iwase, Takuji Shirasawa, Hiroshi Kimura, Ikuo Homma

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


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)-O2 affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% CO2 in O2) and hypoxia (10 and 15% O2 in N2) were assessed in mutant mice expressing Hb Presbyterian (mutation in the β-globin gene, β108 Asn → Lys). O2 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 PCO2 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 O2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures.

Original languageEnglish
Pages (from-to)R747-R753
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4 54-4
Publication statusPublished - 2003 Oct 1


  • Breathing
  • Hypercapnia
  • Hyperoxia
  • Hypoxia
  • Tissue

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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