Respiration 33: 70-83 (1976)

Comparative Studies on the Effect of Oxygen High Pressure (OHP) on Different Species; with Special Reference to the Organ Preservation M. N asseri, R. E isele , D. K ötter , H. K irstaedter and J. W olf Department of Surgery, Free University of Berlin, Berlin Key Words. Hyperbaric oxygenation ■Different species • Lung • Oxygen toxicity • Capillary damage • Organ preservation • OHP effect on fishes Abstract. Different species of animals (warm-blooded, poikilotherms and cold­ blooded) were exposed to oxygen high pressure (OHP) (1-4 ata) for 2-8 h. OHP re­ vealed (a) a different vulnerability in various species; (b) an inverse correlation be­ tween basal oxygen consumption and their vulnerability; (c) the critical point of the toxic effect of OHP in normothermia was an exposition time of 2 h with 2 ata OHP; (d) morphological changes of lung, CNS and vessels - intense folding of alveolar septa with cell hyperplasia and hypertrophy; (e) electron-microscopical demonstra­ tion of damaged endothelial cells with total or partial occlusion of the capillaries.

The progress in experimental and clinical organ transplantation ren­ ders greater importance to different methods of organ preservation. Among other methods, oxygen high pressure (OHP) has been used, though it is well-known that the exposition of small laboratory animals to OHP causes symptoms of oxygen intoxication and organ damage. The ex­ act mechanism of this effect remains unknown. The effect of OHP could perhaps explain the poor results of organ preservation with this method, which has been reported by F ontain et al. [11). It is difficult to come to a clear conclusion about the efficacy of OHP on organ conservation, be­ cause the reports in the literature represent variable pressures, exposition times and different animal species. It is of interest, however, that small animals are more vulnerable to OHP than larger ones. This fact leads to the assumption that perhaps the rate of basal oxygen consumption, as well as the rate of metabolic activity is related to oxygen intoxication and

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Received: October 14, 1974; accepted: January 28, 1975.

N asseri/E isele/K o n

hr/K irstaedter/W olf

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organ damage. The knowledge of this relationship could be of value for experimental organ preservation and choice of species. The experiments reported here represent an attempt to obtain further data concerning the relation between basal metabolism and oxygen intoxi­ cation and organ damage, using OHP on different species with various oxygen consumption rates.

Methods and Materials

Results Tolerance In a pressure range of 1-2 ata OHP and a maximum exposition time of 8 h, there were no clear symptoms of oxygen intoxication in all species, except for a slight hypnotic effect. However, under 3-4 ata OHP, symp­ toms of oxygen intoxication were observed in the CNS, the respiratory organs and the vascular system (table 1). Characteristic behavior as well as different susceptibility of the species were observed under these condi­ tions. Whereas pigeons showed pure neuromuscular reactions in the form of convulsion, guinea pigs developed respiratory disturbances (dyspnea, tachypnea); rats and hamsters both showed the above-mentioned symp-

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Different species with various oxygen consumption rates were used: warm­ blooded animals such as rats (n = 65), guinea pigs (n = 40), and pigeons (n = 42), facultative poikilotherms such as the golden hamster (n = 50) and cold-blooded species such as fish (Tilapia melanopleurd) (n = 47) were exposed to 1-4 ata for a period of 2-8 h. The compression time was 5 min/1 ata, and the decompression time 15 min/1 ata. The following parameters were determined. Tolerance. The appearance time of symptoms and mean survival time of differ­ ent species in defined exposition time were determined. Organ damage. The appearance of the organ edema was assumed to be a sign of the organ damage. The weight coefficient such as lung to heart (L/H) or brain to heart (B/H) was used to measure the quantitative extent of the edema fluid. The coefficients were compared with the normal mean values of control groups. Light-microscopic examination. The lungs in rats, guinea pigs, hamsters and pi­ geons were examined. The results were compared with the selected groups which were exposed to the high air pressure of the same value. The gills and fins of fishes were examined in the same way. Electron-microscopic examination. In 32 rats, which were exposed to 1-4 ata OHP during a period of 2-8 h, the lungs were immediately prepared for electronmicroscopic examination in the usual way [17].

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N asseri/E isele /K ötter /K irstaedter/W olf

Table 1. Symptoms and organ damage of oxygen intoxication in different species due to exposition to OHP (3-4 ata in 8 h) Species

Organ/system

Symptoms

Pigeons

neuromuscular

convulsion

Guinea pigs

respiratory

dyspnea, tachypnea

Rats

respiratory and neuromuscular

dyspnea, tachypnea

Hamsters

respiratory and neuromuscular

convulsion

Fish

vascular system and hydrostatic regulatory mechanism

disturbance of equilibrium

Table 11. Lethality and mean survival time of different species due to exposition to OHP during an 8-hour period Species

Pigeons Rats Guinea pigs Hamsters Fish

Lethality, % OHP, ata 1 2

3

4

0(8) 0(10) 0(10) 0(10) 0(10)

40(8) 27(18) 0(18) 0(10) 0(9)

100 (8) 88 (17) 60 (10) 50 (10) 0(14)

0(8) 0(10) 0(10) 0(10) 0 (10)

Mean survival time+ SD, min (4 ata OHP) 171 ±41 271 ±30 353 ±38 359±40 480(14)

(8) (17) (10) (10)

toms, although with different intensity. Fish demonstrated obvious vascu­ lar changes in their fins and gills, as well as disturbance of the hydrostatic regulatory mechanism. At 1 and 2 ata, all animals survived the maximal exposition time. In 3 and 4 ata there was a differentiation in the susceptibility. Table II demon­ strates the mean survival time and lethality of different species studied during the maximal exposition time of 8 h. The pigeons, the most vulner­ able of all species, showed the shortest survival time at 4 ata. The fish were the most resistant and survived the maximal exposition time without

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The number in each specific group is shown in parentheses.

Effect of Oxygen High Pressure on Different Species

8n

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Fish

Hamster

g uinea pig Rat

a7 A oPigeon

> 2Z0

-i—

- i --------- 1----------1

1.4 0.2 0.6 1.0 Oxygen consumption rate, m l/g/h

1.8

Fig. 1. Relationship between oxygen consumption and mean survival time in dif­ ferent species under influence of OHP (4 ata).

Table III. Oxygen consumption of different species Species

O2 consump­ tion ml/g,/h

Active

Reference

1.500 0.880 0.760 0.360 0.170

42 X

Z euthen [21] K leiber [14] M orrison [16] M artin and F uhrman [15] P rosser and Braun [18]

Warm-blooded Pigeon Rat Guinea pig Dog Human

Poikilotherms Golden hamster

A dolph and L awrow [1]

0.500 0.900

Cold-blooded Fish

0.036 (26 °C)

2X

H all [13]

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lethality. Rats, guinea pigs and golden hamsters ranged between these two extremes. Figure 1 shows the relationship between the above-mentioned results, mean survival time of different species and the basal oxygen con­ sumption (table III). The higher the oxygen consumption rate of the spec­ ies, the higher the susceptibility to oxygen intoxication.

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N a sser i E isele /K ötter /K irstaedter W olf 2 -,

a

— —

Rat Guinea pig

Fig. 2. Change in weight coefficient of brain/heari (a) and lung/heart in different species under the influence of OHP (4 ata) (/>). B/H = Brain/hcart weight of experi­ mental groups; (B/H)„ - brain/heart weight of control groups; L/H = lung/heart weight of experimental groups; (L/H)„ = lung/heart weight of control groups.

Organ Damage Macroscopic examination of the organs showed alterations as dystelectatic lung areas which were found in rats, guinea pigs and also partly in hamsters. In contrast, pigeons showed no organ alterations although they were the most susceptible to OHP as far as survival time is concerned. Hemorrhagic fin infarction with obvious vessel ectasis was found in fish. These changes were most obvious in the tail fins. The gills were whitegrey in color. The group of fish which was exposed to 4 ata of com­ pressed air showed only a disturbance of hydrostatic regulatory system, but without any changes of organs. These organ damages were best dem­ onstrated through measurement of organ weight and creation of compara­ ble weight coefficient. As figure 2 shows, brain weight (B/H) increases were found only in rats. In contrast, all examined species except the pi­ geons showed significant elevation of lung weight (L/H) (p Folding of alveolar septa (3 ata and 6 h exposition time). X 1.400. c Desquamation of alveolar cells and intercellular vacuolization. X 560. d Intense folding of alveolar septa and desquamation of al­ veolar cells (4 ata 2 h). X 560.

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tionship between oxygen consumption and oxygen toxicity correlate with the findings of Donald [9] and Bornstein and Stroink [7], These au­ thors have reported a diminution of oxygen tolerance in humans by physi­ cal exercise. The results of G rossmann and Penrod [12], Bean and co­ workers (2, 3] and Smith el al. [ 191 are similar so far that the substitution of thyroxin in animals decreases and. on the contrary, thyreoectomy or hypophysectomy increase the tolerance of oxygen pressure.

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Effect of Oxygen High Pressure on Different Species

N aSSF.R|/EiSELF./K.ÖTTER/K|RSTAF.DTF.R/WOLF

Fig. 5. Electron-microscopic alteration of rat’s lung under OPH a 3 ata OHP/ 4 h. Swelling of endothelial (E2) cell on the capillary wall. I = Interstitium. b 3 ata OHP/4 h. Swelling of intestinal cells (I). BM Basalmembrane; R - reticulum, AL = alveolar space, c 4 ata OHP/2h. Enlarged erythrocytes (E) in capillaries ex­ tensive swelling of endothelial cells, normal alveolar cells (AL).

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so

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The results of B ert [6] and T homson [20], who found that dogs are more resistant than smaller laboratory animals, could also support this hypothesis, as well as the findings of F alkner and B inger [10] and C leveland [8]. They found a higher tolerance in frogs and thus conclud­ ed that the cold-blooded animals are more resistant than the warm-blood­ ed ones. According to the symptoms of oxygen intoxication, damage could be found in different species. Various organ damage was found in the respir­ ation tract, CNS and vascular system. While pigeons only showed neuro­ muscular symptoms, fish had vascular changes with disturbances of the hydrostatic regulatory system. All other examined species had pulmonary and CNS damages. These findings, especially in pigeons with intensive convulsions, but without pulmonary changes, are in opposition to the hy­ potheses of Bean and co-workers' [4, 5] statement, that the pulmonary changes are indirect results of a neuroendocrine damage. The vascular changes in fish, especially on their fins, are specific for the effect of oxygen. However, the hydrostatic regulation disturbance is not oxygen-specific, and it depends only on the high pressure of the sur­ rounding gas space. This could be shown by a comparable experiment with 4 ata compressed air. The organ damage could be tested in some animal species in the brain and lung by determining the organ weight; in other words, by the creation of a lung/heart and brain/heart coefficient as a measurement for the for­ mation of edema, especially because the weight of the heart does not change very much during the experiment. The relative weight increase of the brain was only testable in rats. But all examined animal species except pigeons showed a significant increase of the relative lung weight (p

Comparative studies on the effect of oxygen high pressure (OHP) on different species; with special reference to the organ preservation.

Different species of animals (warm-blooded, poikilotherms and cold-blooded) were exposed to oxygen high pressure (OHP) (1-4 ata) for 2-8 h. OHP reveal...
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