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  • 1
    Electronic Resource
    Electronic Resource
    Cardiac output, arterial and mixed-venous O2 saturation, and blood O2 dissociation curve in growing rats adapted to a simulated altitude of 3500 m (1972)
    Springer
    Pflügers Archiv 335 (1972), S. 10-18 
    Details
    ISSN: 1432-2013
    Keywords: Cardiac Output ; Blood O2 Dissociation Curve ; High Altitude ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats adapted to a simulated altitude of 3500 m cardiac output measured at hypoxia by the direct Fick principle was significantly lower than in the control animals (mean values 54.3 ml/min and 69.8 ml/min, resp.). The decrease of cardiac output was accompanied by an increase of arterio-venous O2 difference and a decrease of stroke volume in the adapted rats. It is suggested that the decrease of cardiac output might be related to the increase of hematocrit. The adapted rats also showed higher arterial and mixed-venous O2 content (both at hypoxia) and increased O2 capacity. Arterial O2 saturation of the animals previously exposed to simulated high altitude hypoxia was significantly higher (67.3% as against 61.2% in the controls). The standard O2 dissociation curve showed lower oxygen affinity in the blood of the adapted animals but no physiological advantage concerning the transport of O2 to the tissues was found. In another group of animals the Bohr factor was estimated and no difference was found between rat and human blood.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00586931
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  • 2
    Electronic Resource
    Electronic Resource
    Blood gases at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve (1978)
    Springer
    Pflügers Archiv 376 (1978), S. 7-13 
    Details
    ISSN: 1432-2013
    Keywords: Oxygen dissociation curve ; Oxygen transport ; Blood gases ; Hypoxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Theoretical deductions have shown that a shift of the blood O2 dissociation curve (ODC) to the right might improve O2 transport to tissues at normoxia and at mild hypoxia whereas at severe hypoxia the organism should be better off with an ODC shifted to the left (Turek et al., 1973b; Turek and Kreuzer, 1976). The present study was performed in order to ascertain this ambiguous effect of an ODC shift depending on the degree of hypoxia in intact animals. A major displacement of the ODC to the left was achieved in rats by chronic administration of sodium cyanate (NaOCN). Control animals received sodium chloride (NaCl) instead. Arterial and mixed-venous $$P_{{\text{O}}_{\text{2}} }$$ , $$P_{{\text{CO}}_{\text{2}} }$$ , and pH were measured at normoxia and during breathing 14.9, 8.0, or 5.6% O2 in N2 in both groups. From $$P_{{\text{O}}_{\text{2}} }$$ , pH, ODC and arterial hematocrit, arterial and mixed-venous O2 contents were estimated and $$({\text{a}} - {\text{v)}}_{{\text{O}}_{\text{2}} }$$ as an index of blood O2 extraction was obtained. At normoxia and during breathing 14.9% O2 the NaOCN rats had a lower mixed-venous $$P_{{\text{O}}_{\text{2}} }$$ than the NaCl rats without any difference in pH. Arterio-venous O2 difference did not differ at normoxia but was lower in NaOCN rats at 14.9% O2. However, at 8.0 and 5.6% O2 the NaOCN rats had a higher mixed-venous $$P_{{\text{O}}_{\text{2}} }$$ , an increased $$({\text{a}} - {\text{v)}}_{{\text{O}}_{\text{2}} }$$ , and a higher pH (arterial and mixed-venous). At 5.6% O2 the NaCl rats developed a severe acidosis concomitant with pronounced hypocapnia. These findings confirm that rats with a left-shifted ODC have an impaired O2 transport to tissues at normoxia and mild hypoxia but a more efficient O2 transport at severe hypoxia as compared with rats with an unshifted ODC, in agreement with our previous theoretical studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00585241
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  • 3
    Electronic Resource
    Electronic Resource
    Blood volume and body haematocrit of rats native to a simulated altitude of 3500 m (1978)
    Springer
    Pflügers Archiv 374 (1978), S. 285-288 
    Details
    ISSN: 1432-2013
    Keywords: High altitude ; Blood volume ; Red cell volume ; Plasma volume ; Body haematocrit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Circulating blood volume (BV) as the sum of circulating red cell volume (RCV) and plasma volume (PV) was estimated in rats native to a simulated altitude of 3500 m (“natives”), in rats born at sea level and later in life transferred to the simulated high altitude (“newcomers”), and in control sea-level rats. RCV per kg body weight (b.w.) was significantly larger in both “newcomers” and “natives” than in controls. PV per kg b.w. was in the “newcomers” insignificantly and in the “natives” significantly smaller than in the controls. BV per kg b.w. in both high altitude groups tended to be larger than in controls but the difference was not significant. Arterial haematocrit (Ahct) in the “newcomers” was significantly higher than in the controls, and in the “natives” significantly higher than in both other groups. Body haematocrit (the ratio of RCV and BV in per cent) was smaller than Ahct in all groups; this was more pronounced in the “newcomers” than in the controls and even more so in the “natives”. Apparently the haematocrit in the minute vessels of the organs of animals exposed to chronic hypoxic hypoxia increases much less than might be expected from changes of the Ahct. An attempt was made to evaluate the possible error of the more commonly used method of estimating BV, when only RCV, or only PV, is measured, and BV and its complementary fraction are calculated from arterial or venous haematocrit. When, in our results, BV was calculated from RCV and Ahct, the absolute values and also the differences between groups were somewhat underestimated. When BV was calculated from PV and Ahct, the BV itself, and particularly the differences between groups, were overestimated quite considerably. It is suggested that the only safe way to estimate BV is to measure RCV and PV separately.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00585606
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  • 4
    Electronic Resource
    Electronic Resource
    Hypoxic pulmonary steady-state diffusing capacity for CO and cardiac output in rats born at a simulated altitude of 3500 m (1973)
    Springer
    Pflügers Archiv 340 (1973), S. 11-18 
    Details
    ISSN: 1432-2013
    Keywords: Pulmonary Diffusing Capacity for CO ; Cardiac Output ; Oxygen Dissociation Curve ; High Altitude ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats born in the low pressure chamber from sea level parents a higher hypoxic steady-state pulmonary diffusing capacity for CO was found as compared with controls of similar body weight. This difference could be explained by a difference in age or by an increase of blood O2 capacity. There was no difference in alveolar ventilation and alveolar-arterial O2 pressure differences, a lower cardiac output, no difference in arterial O2 tension, no difference in arterial O2 content but a decreased mixed-venous O2 content as compared with control rats measured at hypoxia. A shift of the standard blood O2 dissociation curve to the right was found in the simulated high altitude exposed rats. Calculated mixed-venous O2 pressure was not altered in these rats; since arterial O2 pressure was the same no difference in mean tissue capillary O2 pressure may be presumed as compared with control animals. The results suggest that the first generation of rats exposed to simulated high altitude for their whole life is not only less adapted than animals exposed in their youth (as described in previous work) but that the ability to promote the O2 transport in time of need in rats born in the low pressure chamber is probably even inferior to that of the controls.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00592193
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  • 5
    Electronic Resource
    Electronic Resource
    Arterial blood gases, muscle fiber diameter and intercapillary distance in cardiac hypertrophy of rats with an old myocardial infarction (1978)
    Springer
    Pflügers Archiv 376 (1978), S. 209-215 
    Details
    ISSN: 1432-2013
    Keywords: Blood gases ; Cardiac hypertrophy ; Intercapillary distance ; Myocardial infarction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats with a myocardial infarction due to ligation of the left coronary artery a marked right ventricular hypertrophy developed after 41/2 weeks. At this time no difference against control animals was observed in arterial $$P_{{\text{O}}_2 }$$ , $$P_{{\text{CO}}_2 }$$ , pH, ideal alveolar $$P_{{\text{O}}_2 }$$ , and alveolar-arterial O2 pressure difference, as measured in unanesthetized animals at normoxia. In histological sections of the heart stained by PAS reaction capillaries and muscle fibers were counted, and the mean intercapillary distance and muscle fiber diameter were estimated. In the right ventricle of the rats with myocardial infarction both increased when compared with control animals or with sham-operated rats. Fibercapillary ratio was the same in all three groups. Similar results were obtained in the remaining undamaged tissue of the left ventricle of rats with a myocardial infarction when compared with the left ventricle of control or sham-operated rats. Findings concerning intercapillary distance suggest that also in the myocardium which remains intact during the development of the infarction and later hypertrophies, tissue oxygen transport might be impaired, particularly during a stress situation. Results in the right ventricle of rats with myocardial infarction show an opposite trend against rats exposed chronically to simulated high altitude, where in the hypertrophied right ventricle a shorter intercapillary distance occurs and therefore an improvement of tissue oxygen transport might be expected.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584952
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  • 6
    Electronic Resource
    Electronic Resource
    Myoglobin distribution in the heart of growing rats exposed to a simulated altitude of 3500 m in their youth or born in the low pressure chamber (1973)
    Springer
    Pflügers Archiv 340 (1973), S. 1-10 
    Details
    ISSN: 1432-2013
    Keywords: Myoglobin ; Heart ; High Altitude ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Reynafarje's (1963) spectrophotometric method was modified for the study of myoglobin concentration in rat hearts. The influence of age and body weight was evaluated and the age was found to be better correlated with myoglobin concentration than the weight. The influence of simulated altitude of 3500 m was studied in animals exposed to hypoxia at the age of about 34 days and in animals born in the low pressure chamber. In the first group a higher myoglobin concentration was found but only in the right ventricle, together with unilateral hypertrophy, as compared with control animals. In the group of animals born at simulated altitude a severe cardiomegaly developed which was most pronounced in the right ventricle. The myoglobin concentration in the hearts from this group was unchanged in the right ventricle and was lower in the left ventricle and septum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00592192
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  • 7
    Electronic Resource
    Electronic Resource
    Blood O2 content, cardiac output, and flow to organs at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve (1978)
    Springer
    Pflügers Archiv 376 (1978), S. 201-207 
    Details
    ISSN: 1432-2013
    Keywords: Oxygen dissociation curve ; Oxygen transport ; Cardiac output ; Coronary blood flow ; Blood flow to organs ; Hypoxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A major displacement of the blood O2 dissociation curve (ODC) was achieved in rats by chronic administration of sodium cyanate (NaOCN). Control animals with a normal position of the ODC received NaCl instead. Arterial and mixed-venous O2 content ( $${\text{C}}_{{\text{O}}_{\text{2}} }$$ ) and O2 consumption were measured during breathing room air, 14.9, 8.0, or 5.6% O2 in N2. Cardiac output was obtained by the Fick principle.86RbCl was administered i.v., the rats were killed and the activity of86Rb in heart, spleen, stomach and intestines, liver, kidney, skeletal muscle, and skin was measured. According to Sapirstein (1956, 1958) the fractional uptake of86Rb in these organs corresponds to the fractions of cardiac output supplying these organs, and from the fractional uptake and cardiac output the nutritional blood flow may be calculated. Arterial and mixed-venous $${\text{C}}_{{\text{O}}_{\text{2}} }$$ was larger in the NaOCN than in the NaCl rats at all levels of oxygenation. At normoxia and 14.9% O2 the venous $${\text{C}}_{{\text{O}}_{\text{2}} }$$ was enlarged more than the arterial one, and so the arterio-venous O2 difference [ $$\left( {{\text{a}} - {\text{v}}} \right)_{{\text{O}}_{\text{2}} }$$ ] as an index of the O2 extraction in the body was smaller in the rats with a left-shifted ODC. However, at more severe hypoxia (8.0 and 5.6% O2) the arterial $${\text{C}}_{{\text{O}}_{\text{2}} }$$ in the NaOCN rats was enlarged more than the mixed-venous one, resulting in a larger $$\left( {{\text{a}} - {\text{v}}} \right)_{{\text{O}}_{\text{2}} }$$ (and therefore O2 extraction) when compared with the NaCl animals. Cardiac output was larger in the NaOCN than in the NaCl rats at 14.9 and 5.6% O2, when expressed per kg body weight. At 14.9% O2 the augmented cardiac output compensated for the lower O2 extraction when compared with the NaCl animals. At 5.6% O2 the NaOCN rats had both a larger ( $$\left( {{\text{a}} - {\text{v}}} \right)_{{\text{O}}_{\text{2}} }$$ ) and cardiac output than the NaCl animals. In the NaCl rats the decreased O2 extraction was not compensated for by an augmented cardiac output and therefore their O2 consumption was not only lower than that of the NaOCN rats but decreased even below the normoxic value of the NaCl rats. Coronary blood flow was increased in both NaOCN and NaCl animals at deep hypoxia to about the same extent, but due to a much lower arterial $${\text{C}}_{{\text{O}}_{\text{2}} }$$ of the NaCl animals, their O2 supply to the heart was lower than that of the NaOCN rats. The nutritional blood flow to spleen, kidney, liver, stomach and intestines, and skin in ml/min · g was lower in the rats with a normal position of the ODC than in those with a left-shifted ODC. This, together with the low arterial $${\text{C}}_{{\text{O}}_{\text{2}} }$$ of the NaCl rats, suggests a serious compromising of the O2 supply to these organs. Results of this study support the conclusion of our theoretical studies (Turek et al., 1973; Turek and Kreuzer, 1976) that a shift of the ODC to the left might be disadvantageous for the O2 transport to tissues at mild hypoxia, but advantageous at severe hypoxia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584951
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  • 8
    Electronic Resource
    Electronic Resource
    Coronary blood flow in rats native to simulated high altitude and in rats exposed to it later in life (1975)
    Springer
    Pflügers Archiv 355 (1975), S. 49-62 
    Details
    ISSN: 1432-2013
    Keywords: High Altitude ; Coronary Blood Flow ; Cardiac Output ; Cardiac Hypertrophy ; Rat ; TissueP O 2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats exposed to a simulated high altitude of 3500 m for their whole prenatal and postnatal life a severe cardiac hypertrophy develops. In rats born and first staying 5 weeks at sea level and then being exposed to simulated high altitude, only a unilateral right cardiac hypertrophy occurs. In both groups nutritional coronary blood flow was estimated in left ventricle, right ventricle, and septum and was compared with control animals of similar age. Coronary blood flow was measured at hypoxia in all groups. At first cardiac output was determined by the Fick principle, then86Rb was applied and the animals were killed after 55 sec. Activity of86Rb was measured in both cardiac ventricles and septum and the fractional uptake was calculated. According to Sapirstein (1956, 1958) the distribution of86Rb follows the distribution of cardiac output and from both these data the nutritional blood flow to the parts of the heart may be estimated. Cardiac output was similar in rats exposed to simulated high altitude later in life (“newcomers”) and in control animals, but it was significantly lower in rats born in the low pressure chamber (“natives”). Fractions of cardiac output supplying cardiac ventricles and septum in rats from both hypoxic groups were significantly higher than in control animals. In the “natives” they were significantly higher than in the “newcomers”. The fractions of cardiac output in both “newcomers” and “natives” remained significantly higher than those of the control animals, also when calculated per gram of heart tissue. Nutritional coronary blood flow (in ml/min) was higher in both ventricles and septum of the “newcomers” and in the right ventricle of the “natives”, and lower in the septum of the “natives”, when compared with control animals. Coronary blood flow per gram of heart tissue (in ml/min·g) was significantly higher in all cardiac parts of the “newcomers”, but it was about the same in all cardiac parts of the “natives” when compared with controls. The importance of observed changes concerning myocardial tissue oxygenation is analyzed by using Krogh's cylindrical tissue model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584799
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  • 9
    Electronic Resource
    Electronic Resource
    Oxygen transport in guinea pigs native to high altitude (Junin, Peru, 4,105 m) (1980)
    Springer
    Pflügers Archiv 384 (1980), S. 109-115 
    Details
    ISSN: 1432-2013
    Keywords: High altitude ; O2 transport ; O2 dissociation curve ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In guinea pigs native to high altitude in the Andes (Peru) the arterial and mixed-venousP O 2,P CO 2, pH, and O2 content were measured at high altitude during breathing ambient air. Identical measurements were done in Nijmegen, The Netherlands, on sea-level natives and on guinea pigs exposed for 4–5 weeks to simulated altitude in a low pressure chamber, while breathing ambient air (normoxia) or an hypoxic mixture of O2 in N2 with aP I O 2 similar to that of the ambient air at high altitude. A standard blood O2 dissociation curve (ODC) was estimated in vitro (at pH=7.4 and 37.5°C), and a standard in vivo ODC was derived from measuredP O 2,S O 2 and pH in all three groups. Both guinea pigs native to natural or simulated high altitude had a higher hematocrit and blood O2 capacity than sea-level controls. These increased altitude values were, however, almost the same as the sea-level values of man or rat. No difference in the ideal alveolararterialP O 2 difference or lung diffusing capacity for O2 was found between (natural or simulated) high altitude animals and their corresponding controls, when measured at hypoxia. Mixed-venousP O 2 was higher in guinea pigs from the natural high altitude (but not in those from the low pressure chamber) when compared with control sea-level natives studied at hypoxia. No difference among groups in cardiac output was found, while breathing the same inspiratory mixture. In the guinea pigs native to high altitude a higher P50 and a lower Hill numbern for the in vitro ODC were found when compared with the controls or with the guinea pigs exposed to simulated high altitude. This was not observed when the ODC's were estimated in vivo. The rather modest polycythemic response to high altitude in guinea pigs coincides with a low value of P50, when related to body weight. In this respect the guinea pig seems to be more closely related to the typical high altitude mammals like Andean camelids and rodents than to man or rat that respond to high altitude with a pronounced polycythemia and possess a rather high P50 with respect to body weight.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00584425
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  • 10
    Electronic Resource
    Electronic Resource
    Experimental myocardial infarction in rats acclimated to simulated high altitude (1980)
    Springer
    Basic research in cardiology 75 (1980), S. 544-554 
    Details
    ISSN: 1435-1803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei Ratten, die während 6–7 Wochen einer simulierten Höhe von 3500 oder 6000 m ausgesetzt waren, wurde eine Herzmuskelnekrose hervorgerufen durch Abbindung der linken Koronararterie in der Nähe ihres ursprungs, durch Abbindung des absteigenden Astes der linken Koronararterie (wahre Infarkte) oder durch Verabreichung großer Dosen von Isoprenalin. Dieselben Prozeduren wurden bei Kontrollratten auf Meereshöhe angewandt. Das Ausmaß der Nekrose 24 Stunden nach ihrer Hervorrufung wurde aus der Aktivität der Kreatinphosphokinase im Gewebe des linken Ventrikels und bei Ratten, die kontinuierlich einer Höhe von 6000 m ausgesetzt waren, auch durch Messung der histochemisch mit Phosphorylase markierten Nekrose in histologischen Schnitten geschätzt. Bei Ratten, die einer Höhe von 3500 m ausgesetzt waren, war das Ausmaß der durch Isoprenalin hervorgerufenen Nekrose kleiner als bei den Kontrollen, aber bei wahren Infarkten bestand kein Unterschied gegenüber den Kontrollen. Bei Ratten, die intermittierend einer Höhe von 6000 m ausgesetzt waren, wurde im Vergleich mit Ratten auf Meereshöhe bei keinem Typ von experimenteller Nekrose ein Unterschied im Ausmaß gefunden. Bei Ratten, die kontinuierlich einer Höhe von 6000 m ausgesetzt waren, war das Ausmaß aller Typen von experimenteller Nekrose geringer als bei den Kontrolltieren. In histologischen Schnitten von Herzen mit wahrem Infarkt war es möglich, zwischen intaktem Gewebe, einer Zone totaler Nekrose und einer Zone partieller Nekrose zu unterscheiden. Unabhängig davon, ob der Hauptstamm oder der absteigende Ast der linken Koronararterie abgebunden wurde, ergaben sich folgende Befunde: Das Ausmaß der Zone totaler Nekrose war kleiner bei Ratten, die kontinuierlich einer Höhe von 6000 m ausgesetzt waren, die Zone partieller Nekrose war größer nur bei Ratten mit Abbindung des Stammes, und die Ausdehnung des intakten Herzmuskels unterschied sich nicht von jener der Kontrollratten auf Meereshöhe mit demselben Typ von Infarkt.
    Notes: Summary In rats exposed to a simulated high altitude of 3500 m or 6000 m for 6–7 weeks, myocardial necrosis was produced by ligation of the left coronary artery close to its origin, by ligation of the descending branch of the left coronary artery (true infarcts), or by administration of a large dose of isoprenaline. The same was done in control sea-level animals. The extent of the necrosis 24 hours after its induction was estimated from the activity of creatine phosphokinase in the tissue of the left ventricle and, in rats continuously exposed to 6000 m, also by measuring the surface of necrosis marked histochemically with phosphorylase activity in histological slides. In rats continuously exposed to 3500 m the extent of the isoprenaline-induced necrosis was smaller than in the controls, but there was no difference in true infarction. In rats intermittently exposed to 6000 m, no difference in the extent of any type of experimental necrosis was found when compared with sea-level rats. In rats continuously exposed to 6000 m, the extent of all types of experimental necrosis was smaller than in control animals. In histological sections of hearts with true infarctions it was possible to distinguish between the intact tissue, a zone of total necrosis and a zone of partial necrosis. Whether the main trunk or the descending branch of the left coronary artery was ligated, the extent of the zone of total necrosis in rats continuously exposed to 6000 m was smaller, the zone of partial necrosis was larger only in rats with a ligature of the trunk, and the extent of intact myocardium was not different when compared with control sea-level animals with the same type of myocardial infarction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01907836
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