1. Recently, we have demonstrated that hypoxic breathing is followed b
y an increase in plasma digoxin-like substance in normal men. 2. This
study was undertaken in order to evaluate whether or not a low arteria
l O-2 partial pressure is combined with an increase in plasma digoxin-
like substance in chronic pathological conditions also. 3. Sixteen mal
e patients (mean age 53.1+/-3.7 years) affected by chronic obstructive
pulmonary disease of a mild stage were studied. They were further sub
-divided according to their arterial O-2 partial pressure into 'mild h
ypox;ic' (n = 8, mean age 52.5+/-2.7 years), with an arterial O-2 part
ial pressure between 66 and 75 mmHg, and 'severe hypoxic' (n = 8, mean
age 54.3+/-5.1 years), with an arterial O-2 partial pressure less tha
n or equal to 65 mmHg, groups. Seven healthy men (mean age 48.5+/-4.8
years) voluntarily participated as the control group. 4. Plasma digoxi
n-like substance levels were significantly higher in 'severe hypoxic'
patients (203.5+/-9.9 pg/ml) than in both 'mild hypoxic' patients (169
.5+/-31.4 pg/ml, P<0.02) and normal subjects (158.9+/-12.4 pg/ml, P<0.
0001) and were directly correlated with urinary Na+ excretion (severe
hypoxic group, r = 0.756, P<0.007; mild hypoxic group, r = 0.789, P<0.
02). Considering the two hypoxic groups together, plasma digoxin-like
substance levels were negatively correlated with arterial O-2 partial
pressure (r = -0.740, P<0.001). However, when patients were subdivided
according to the degree of hypoxia, the negative correlation between
arterial O-2 partial pressure and plasma digoxin-like substance persis
ted only in severe hypoxic patients (r = -0.761, P<0.03). 5. These res
ults indicate a clear linkage between blood O-2 and endogenous digoxin
-like substance regulation. In particular, hypoxia may be regarded as
an important stimulus for the release of the endogenous digoxin-like s
ubstance in man.