United States Department of Transportation
i
Changes in the oxygen-hemoglobin dissociation curve and time of useful function at hypobaric pressures in rats after chronic oral administration of propranolol.
-
1980-05-01
-
[PDF-457.96 KB]
Details:
-
Creators:
-
Corporate Creators:
-
Corporate Contributors:
-
Subject/TRT Terms:
-
Publication/ Report Number:
-
Resource Type:
-
Geographical Coverage:
-
Corporate Publisher:
-
Abstract:Twenty rats were given propranolol, 1.8 mg/kg body weight, by mouth for 12 days. On day 13, these and 20 control rats were tested for time of useful function (TUF) after rapid decompression in a hypobaric chamber. The criterion for TUF was the animal's ability to remain upright in a motor-driven exercise wheel. The decompression profile was achieved by rapidly reducing the pressure to a level equivalent to an altitude of 34,000 ft (10,363 m), holding for 1 min, then recompressing and holding at 29,000 ft (8,839 m) for the remainder of the test. On day 13 the propranolol-treated rats had a significant shift to the right in the oxygen-hemoglobin dissociation curve (ODC), their average P50 was about 3.5 torr greater than that of control animals. Although shifts to the right in the ODC normally occur during adaptation to altitudes, this was of no advantage to the drug-treated group, which had an average TUF of only about 170 s (approximately 50 s less than that of control rats). This finding is consistent with the results of Eaton et al., who found that rats with left-from-normal shifts in the ODC survived longer than did control rats at altitudes approximatley equal to those used in the present study. In other expermients we showed that one metabolite of propranolol, 4-hydroxypropranolol, can produce rightward shifts in the ODC. This result may help explain why chronic administration of the drug causes such shifts, though its concentration in the blood is far less that that required to produce the effect in vitro. Decrements in the TUF seen in these and other (FAA Office of Aviation Medicine Report No. AM-79-10) experiments were probably the result of several mechanisms, including shifts in the ODC, central depression, and cardiovascular effects.
-
Format:
-
Collection(s):
-
Main Document Checksum:
-
Download URL:
-
File Type:
