title: Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.
abstract: BACKGROUND
  Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.
  
  
  METHODS
  165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.
  
  
  RESULTS
  There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.
  
  
  CONCLUSIONS
  Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses.
authors.affiliation: Imperial College School of Medicine, Imperial College, London, United Kingdom; National Heart and Lung Institute (NHLI) Cardiovascular Science, Imperial College, London, United Kingdom; Respiratory Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Vatshalan
authors.initials: V
authors.lastname: Santhirapala
authors.affiliation: Respiratory Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Louisa C
authors.initials: LC
authors.lastname: Williams
authors.affiliation: Respiratory Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Tighe
authors.affiliation: Department of Imaging, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: Jackson
authors.affiliation: National Heart and Lung Institute (NHLI) Cardiovascular Science, Imperial College, London, United Kingdom; Respiratory Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Shovlin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood; D001165:Arteriovenous Malformations / Q000150:complications; D056352:Athletes; D001784:Blood Gas Analysis; D004909:Erythrocyte Indices; D015444:Exercise; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*; D011086:Polycythemia / Q000097:blood* / Q000209:etiology / Q000503:physiopathology*; D011651:Pulmonary Artery / Q000002:abnormalities; D011667:Pulmonary Veins / Q000002:abnormalities; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D007501:Iron; D010100:Oxygen