Flückiger, E.

Verzár, F.

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LACK OF ADAPTATION TO LOW OXYGEN PRESSURE IN AGED ANIMALSE. FLUCKIGER, D.Sc, AND F. VERZAR, M.D.(From the Physiological Institute, University of Basel, Basel, Switzerland)Adaptation to a barometric pressure ofabout half an atmosphere, or the equivalentlow partial oxygen pressure, necessitates vari-ous adjustments in the animal body. Respira-tion and circulation, as well as erythrocyteand hemoglobin production, are changed.We found (1) it to be a very characteristicphenomenon that, in rats, after lowering theatmospheric pressure to 350 mm. Hg (cor-responding to 6,500 M. simulated altitude),the rectal temperature drops several degreesin a few hours. In about 4 or 5 days bodytemperature is restored to normal, althoughthe pressure was kept low. It was alsodemonstrated (2) that rats kept at 350 mm.Hg for a fortnight developed a status, whichwe called "retained adaptation," i. e., if theseanimals were brought to atmospheric pres-sure (732 mm. Hg at Basel) and within a fewdays returned to 350 mm. Hg, only a slightdecrease in rectal temperature was observed.At 732 mm. Hg this status of retained adapta-tion slowly returned to the full reaction, until,10 days later, when exposed to 350 mm. Hg,the same drop of rectal temperature was seenas originally.This drop of temperature and its restora-tion to normal is an objective sign of adapta-tion which can easily be observed. We haveused this phenomenon in the present publica-tion to investigate whether this adaptation tolow pressure is the same in young, adult, andaged animals.METHODSThe technique of these experiments wassimilar to that employed in our earlier studies(1). Sixty-four white male rats of our labora-tory stock, 45 to 570 days old, were used ingroups of 4 animals for each age level, givinga total of 16 groups. Of these, 2 groups weretested more than once: 1 group was studiedwhen 2?2 and 4?2 months (70 and 135 days)old (experiments 74b and 79b), and 1 grxipwas tested at the age of 12, 14, and 20 months(360, 420, and 600 days) (experiments 74a,79a, and 85a).Submitted for publication December 15, 1954.Published on a grant from the Forest Park Foundation tothe Journal of Gerontology.The rats were fed with a standard diet adlibitum. They were placed in a tank of about125 L. capacity, in which the pressure wasdiminished to 350 mm. Hg and kept constantat about ± 10 mm. Hg. At 350 mm. Hgthere was an air flow through the tank ofabout 4.5 L. per minute. The temperaturewithin the tank was about 22 C. During thefirst 24 hours the tank was opened severaltimes in order to observe the drop in rectaltemperature. During the next days the tankwas only opened once daily, the animals takenout for about 20 minutes, and their rectaltemperature measured with a mercury ther-mometer. This was done regularly at about10 to 11 a.m., 24 hours after the last feeding.Afterwards the rats were placed back intothe tank, with fresh food and water. The tankwas equipped with a window allowing ob-servation of the behavior of the rats. Theweight of the animals was taken at regularintervals and in several series also blood hemo-globin was measured by the Sahli method.Retained adaptation was tested in 13 ofthe 16 groups. This was done in the follow-ing way: After a period of about 14 days ofadaptation to 350 mm. Hg the rats were keptat 730 mm. Hg for 48 hours and then exposedagain to 350 mm. Hg. Since retained adapta-tion never lasts longer than about a fortnight,there is no danger that the reaction at a latertrial was influenced by the first exposure tolow barometric pressure. However, the re-sults in these groups were checked with thoother groups which were only used once.RESULTSThe results of our experiments are tabu-lated as mean values for each group in table1. There are always individual differencesin each group. The drop of body temperatureand the time in which normal body tempera-ture is restored should be compared. Ex-amples of temperature curves of different agegroups are shown in figure 1 and 3.Table 1 shows that there is no differencein the initial drop of rectal temperature be-tween young and old animals; their maximalvalue was 5.3 C. in 6 weeks (42 days) old306ADAPTATION TO LOW OXYGEN PRESSURETABLE 1. BODY TEMPERATURE ADAPTATION OF RATS TO REDUCED BAROMETRIC PRESSURE.307Series930783 b8891Sib74 b9079 b85 b8074 aS3 a79 a8985 aAge andNumber ofAnimalshx/i weeksn = 76 weeks8 weeksn = 4S weeks9 weeks9 weeks2V2 months3 months4^2 months5 months7 months12 months14 months14 months19 monthsn = 420 monthsAdaptationRt*atBeginningCC.)37.537.637.237.437.337.638.037.338.173.237.238.137.438.037.637.2MaximalDrop ofRt CC.)4.75.33.45.24.13.44.54.64.93.44.24.73.55.25.34.9Rt RestoredDay3.-4.4.3.7.5.4.5.5.5.4.4.5.10.5.10.5.10.5.10.16.5.11.Rt CC)37.237.437.237.437.237.837.937.338.037.237.336.936.335.836.036.336.035.236.136.136.635.4RtatBeginningCC)—37.237.437.0—37.537.6—38.037.236.437.737.337.437.437.2Retained AdaptatioiMaximalDrop ofRt CC)—2.21.82.7—3.20.8—3.31.91.02.32.64.13.83.81Rt RestoredDay—4.1.2.—2.1.—2.2.1.3.3.2.3.3.Rt CC)—37.037.236.9—37.437.7—37.837.136.537.336.035.635.435.6Remarks72 hours at730 mm. Hgno restoration!no restorationno restorationno restorationno restoration*1UfNo= Rectal temperature in °C. at 10:00 to 11:00 a.m.restoration of Rt having taken place Rt values are given for certain days.308 FLVCKIGER AND VERZAR(group 67) as well as in 19 months (570days) (group 89) old rats.The difference between young and old ratslies in the ability to restore the original bodytemperature. In 40 to 210 day (7 months)old animals, restoration is complete in 3 to5 days; on the third day of low pressure theirrectal temperature is mostly above 37 C. andoften as high as 37.8 to 38.0 C. Figure 1shows one of these groups. The 20 rats of12, 14, 19, and 20 months of age (groups 74a,83a, 79a, 89, 85a) were unable to restore theirbody temperature, and figure 3 is an exampleof how restoration of the body temperature isoften at first attempted and how later it againfalls. On the tenth day at low pressure bodytemperature was between 35.4 and 36.3 C.Thus, in the course of aging, the rats losethe ability to restore normal body tempera-ture at low oxygen pressures.Retained adaptation, i. e., the reaction to350 mm. Hg of formerly adapted rats after2 to 3 days of a pressure of 732 mm. Hg toa new decreased pressure of 350 mm. Hgwas also different in old animals. The oldestgroups (79a, 89, 85a) showed the largest dropin body temperature, as much as without aprevious adaptation. More characteristic isthat while the young animals restored bodytemperature within one to two days (fig. 2)in the rats of 14, 19, and 20 months of agethere was no return to normal body tempera-ture, even after the third day of exposure tolow barometric pressure. Some of the oldanimals died after exposure to low atmos-pheric pressure (fig. 4), which never oc-curred with young animals.It is known that exposure to low barometricpressure, especially during the first few days,results in a decrease of body weight, or in-hibits growth in young animals through a de-crease of food intake (4) and the body watercontent (3). The data shown in table 2 areexamples.In order to characterize the influence oflow barometric pressure on the different agegroups by another criterion, the hemoglobinof the blood from the tip of the tail was de-termined in several series. In rats 2 months•1 -H 1 1—+•-35-34-33-32-31-300 2 4 6 8 12h 1 2FIG. 1. Series 74b, 4 male rats, 2x/> months old,adaptation to 350 mm. Hg in 2 days.0 2 4 6 8 12h 1 2dFIG. 2. Retained adaptation of the same animals(Series 74b) after 48 hours at 730 mm. Hg and thenagain at 350 mm. Hg.ADAPTATION TO LOW OXYGEN PRESSURE 309TABLE 2. CHANGES IN WEIGHT OF MALE RATS OF DIFFERENT AGES EXPOSED TO LOW OXYGEN PRESSURE.Series83 b88918083 a89Age andNumber ofMale Rats2 months2 months9 weeks7 monthsn = 414 months19 monthsn = 4MeanInitialWeight (Gm.)9889115216334289Days at350 Mm. Hg101715101017MeanWeight(Gm.)10294108202309275Difference(Gm.)+ 4+ 5- 7- 1 4- 2 5- 2 3old the hemoglobin changes were followedduring the first 5 days by daily deteiTninations(group 83b). It was found that an increasein hemoglobin started only on the fifth dayof exposure, reaching 130-142 per cent onthe tenth day (100 per cent = 16 Gm. hemo-globin per 100 cc) . In table 3 hemoglobinvalues estimated after different periods of ex-posure to 350 mm. Hg are shown. The meanhemoglobin content at 732 mm. Hg of 14rats 2 to 14 months old was found to be 106per cent (range 99-115) when 100 per cent= 16 Gm. Hb per 100 ml. From the table30-0 2 4 6 8 12h 1 2 4 6 9 1113dFIG. 3. Series 89b, 4 male rats, 19 months old,incomplete adaptation to 350 mm. Hg.0 2 4 6 8 12h 1 2 4 6dFIG. 4. No retained adaptation of the same ani-mals (Series 89b) after 48 hours at 730 mm. Hgand then again at 350 mm. Hg.310 FLVCKIGER AND VERZARTABLE 3. CHANGES IN MEAN BLOOD HEMOGLOBIN IN MALE RATS AT DIFFERENT AGES,EXPOSED TO LOW OXYGEN PRESSURE.SeriesControls at 732 mm. Hg83 b817083 a85 aAge andNumber ofAnimals2-14 monthsn = 142 monthsn = 49 weeksn = 43^2 monthsn = 414 monthsn = 420 monthsn = 4Days at350 Mm. Hg10)110 [J141011MeanHemoglobin %(100 = 16 Gm. %)106137166158149Lowestand HighestValue99-115125-145146-180155-166146-152it follows that the capacity of the rats to in-crease the blood hemoglobin did not diminishup to 20 months of age (table 3).DISCUSSIONIt is not definitely known what causes thedrop of body temperature at the beginning ofthe exposure to low partial oxygen pressure.Since there are no proofs of altered blood cir-culation under low pressure, the most prob-able explanation is a diminished heat produc-tion. Then in the course of adaptation of theyoung animals, the metabolism which is neces-sary for normal heat production is increased.In aged animals, however, this increase inmetabolic activity to restore and maintainnormal body temperature, i. e., their adapta-tion capacity, is diminished; they are alsobarely able to reach a state of adaptationwhich can be retained when kept at 732mm. Hg.This inability to adapt to low oxygen pres-sure is an astonishingly early sign of aging.It is, so far, the only example of functionaladaptation which disappears with age thatwe were able to observe.Our experiments show at the same timethat the reactivity of the bone marrow in re-spect to hemoglobin production under lowoxygen pressure was not decreased in theold animals. This finding is in line with theresults of other experiments, where no de-crease in compensatory hypertrophy of thekidney or of the adrenal cortex could be seenin old animals (5).From this point of view the demonstrationof a decrease of metabolic adaptation to lowoxygen pressure in aging rats becomes an es-pecially interesting sign of aging.SUMMARY1. Adaptation to low barometric pressure(350 mm. Hg) was studied in 64 male ratsbetween the ages of 45 to 570 days (2 to 20months).2. Adaptation was tested by the decreaseand the restoration of body temperature dur-ing 15 days' continuous exposure to a lowatmospheric pressure of 350 mm. Hg. Inaddition retained adaptation was also testedafter an additional study of 48 hours at nor-mal barometric pressure (732 mm. Hg atBasel).3. Fourteen to 20 month old rats are com-pletely unable to restore the normal bodytemperature after the initial drop during thefirst few hours of exposure to low barometricpressure. They also show a decreased re-ADAPTATION TO LOW OXYGEN PRESSURE 311tained adaptation. This is in contrast tothe findings in young animals.4. There is no significant difference inthe increase of blood hemoglobin betweenyoung and old rats in response to a 10 to 15day exposure to 350 mm. Hg.REFERENCES1. Fliickiger E., and Verzar, F.: Senkung und Res-titution der Korpertemperatur bei niedrigem at-mospharischem Druck und der Einfluss von Thy-reoidea, Hypophyse und Nebennierenrinde aufdieselbe. Helvet. physiol. et pharmacol. acta, 10:349-359, 1952.2. Fliickiger, E., and Verzar, F.: Ueberdanern derAdaptation an niedrigen atmospharischen Druck,nachgewiesen an der Warmeregulation. Helvet.physiol. et pharmacol. acta, 11: 67-72, 1953.3. Picon-Reategui, E., Fryers, G. R., Berlin, N. I.,and Lawrence, J. H.: Effect of Reducing the At-mospheric Pressure on Body Water Content ofRats. .Am. J. Physiol, 172: 33-36, 1953.4. Sundstrom, E. S., and Michaels, G.: The Ad-renal Cortex in Adaptation to Altitude, Climateand Cancer. University of California Press, Berk-eley and Los Angeles, 1942, p. 475. Verzar F., and Fliickiger, E.: Adaptation to LowAtmospheric Pressure. Symposia and Abstracts,International Association of Gerontology, ThirdCongress, 1954, p. 263.

Lack of Adaptation to Low Oxygen Pressure in Aged Animals

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