Effects of crocetin on pulmonary gas exchange in foxhounds during hypoxic exercise

The carotenoid compound crocetin has been hypothesized to enhance the diffu sion of O-2 through plasma, and observations in the rat and rabbit have rev ealed improvement in arterial Po-2 when crocetin is given. To determine whe ther crocetin enhances diffusion of O-2 between alveolar gas and the red bl ood cell in the pulmonary capillary in vivo, five foxhounds, two previously subjected to sham and three to actual lobectomy or pneumonectomy, were stu died while breathing 14% O-2, at rest and during moderate and heavy exercis e before and within 10 min after injection of a single dose of crocetin as the trans isomer of sodium crocetinate (TSC) at 100 mu g/kg iv. This dose i s equivalent to that used in previous studies and would yield an initial pl asma concentration of 0.7-1.0 mu g/ml. Ventilation-perfusion inequality and pulmonary diffusion limitation were assessed by the multiple inert gas eli mination technique in concert with conventional measurements of arterial an d mixed venous O-2 and CO2. TSC had no effect on ventilation, cardiac outpu t, O-2 consumption, arterial Po-2/saturation, or pulmonary O-2 diffusing ca pacity. There were minor reductions in ventilation-perfusion mismatching (l ogarithm of the standard deviation of perfusion fell from 0.48 to 0.43, P = 0.001) and in CO, output and respiratory exchange ratio (P = 0.05), which may have been due to TSC or to persisting effects of the first exercise bou t. Spectrophotometry revealed that TSC disappeared from plasma with a half time of similar to 10 min. We conclude that, in this model of extensive pul monary O-2 diffusion Limitation, TSC as given has no effect on O-2 exchange or transport. Whether the original hypothesis is invalid, thy dose of TSC was too low, or plasma diffusion of O-2 is not rate Limiting without TSC ca nnot be discerned from the present study.