Increase in bilirubin levels of patients with obstructive sleep apnea in the morning--a possible explanation of induced heme oxygenase-1.
OBJECTIVE
In the absence of heme oxygenase-1 (HO-1), which catalyzes the oxidation of heme to generate carbon monoxide and indirect bilirubin, hypoxia induces severe right ventricular dilation and infarction. Despite severe hypoxemia during sleep, patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) rarely die during sleep. We hypothesized that apnea-related hypoxemia would induce HO-1 and increase bilirubin levels in the morning in OSAHS patients. Therefore, bilirubin levels in OSAHS patients were analyzed before and after nasal continuous positive airway pressure (nCPAP) therapy.


METHODS
Bilirubin levels in the afternoon before sleep and in the morning immediately after sleep were determined before and after nCPAP treatment.


METHODS
University Hospital in Kyoto, Japan.


METHODS
The subjects were 22 patients with OSAHS (mean (SEM) apnea and hypopnea index of 60 (5)) who were treated with nCPAP and 13 controls.


METHODS
N/A.


RESULTS
Before nCPAP treatment, total after-sleep bilirubin level was significantly higher than the pre-sleep level (p<0.0001). The difference between the serum indirect bilirubin levels in the morning versus in the previous afternoon [D-(M-A)-IB] decreased significantly with nCPAP treatment (p<0.01). The magnitude of decrease in D-(M-A)-IB after nCPAP treatment correlated significantly with changes in the percent time spent with arterial O2 saturation below 90% (r=0.44; p=0.04) and 85% (r=0.49; p=0.02), respectively, during sleep after nCPAP treatment.


CONCLUSIONS
The increase in bilirubin level by HO-1 might protect OSAHS patients from disorders related to hypoxemia.
Department of Physical Therapeutics, Kyoto University Hospital of Medicine, Japan. chink@kuhp.kyoto-u.ac.jp
K
K
Chin
M
M
Ohi
K
K
Shimizu
T
T
Nakamura
F
F
Miyaoka
M
M
Mishima
T
T
Nakamura
D001663:Bilirubin / Q000097:blood*; D002940:Circadian Rhythm / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D017286:Polysomnography; D011175:Positive-Pressure Respiration; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000175:diagnosis / Q000628:therapy
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001663:Bilirubin