Mechanisms that modulate peripheral oxygen delivery during exercise in heart failure

Tomohiko Kisaka, William W. Stringer, Akira Koike, Piergiuseppe Agostoni, Karlman Wasserman

Research output: Contribution to journalArticlepeer-review


Oxygen uptake (V O2) measured at the mouth, which is equal to the cardiac output (CO) times the arterial-venous oxygen content difference [C(a-v)O2], increases more than 10- to 20-fold in normal subjects during exercise. To achieve this substantial increase in oxygen uptake [V O2 = CO×C(a-v)O2] both CO and the arterial-venous difference must simultaneously increase. Although this occurs in normal subjects, patients with heart failure cannot achieve significant increases in cardiac output and must rely primarily on changes in the arterial-venous difference to increase V O2 during exercise. Inadequate oxygen delivery to the tissue during exercise in heart failure results in tissue anaerobiosis, lactic acid accumulation, and reduction in exercise tolerance. H1 is an important regulatory and feedback mechanism to facilitate additional oxygen delivery to the tissue (Bohr effect) and further aerobic production of ATP when tissue anaerobic metabolism increases the production of lactate (anaerobic threshold). This H1 production in the muscle capillary promotes the continued unloading of oxygen (oxyhemoglobin desaturation) while maintaining the muscle capillary PO2 (Fick principle) at a sufficient level to facilitate aerobic metabolism and overcome the diffusion barriers from capillary to mitochondria ("critical capillary PO2," 15-20 mm Hg). This mechanism is especially important during exercise in heart failure where cardiac output increase is severely constrained. Several compensatory mechanisms facilitate peripheral oxygen delivery during exercise in both normal persons and patients with heart failure.

Original languageEnglish
Pages (from-to)S40-S47
JournalAnnals of the American Thoracic Society
Publication statusPublished - Jul 1 2017


  • Bohr effect
  • Critical capillary PO
  • Fick's Law of Diffusion
  • Lactate threshold
  • Oxygen dissociation from hemoglobin during exercise

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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