Z. Turek

Advantage or disadvantage of a decrease of blood oxygen affinity for tissue oxygen supply at hypoxia

SummaryA shift of the oxygen dissociation curve to the right is often interpreted as an adaptation to hypoxia favorable for tissue oxygen supply. However, animals native to high altitude tend to show a rather high oxygen affinity. In order to elucidate this apparent discrepancy we investigated by numerical computer studies 1. the effect of a shift of the dissociation curve to the right as reflected in the mixed venous oxygen pressure, and 2. the role of this displacement in pulmonary gas exchange with particular reference to the alveolar-arterial oxygen pressure difference and the pulmonary diffusing capacity for oxygen. A right shift had a favorable effect only in the range of moderate hypoxia (and of normoxia) whereas there was a detrimental effect with severe hypoxia. The most important criterion for this distinction was the direction of the change in steepness of the physiological dissociation curve (straight line between arterial and venous points). A favorable effect was associated with a steeper slope after the shift, an unfavorable effect with a less steep slope. There was only a minor influence of a right shift on the oxygen diffusion gradient in the lung. Comparison between man (higher affinity) and rat (lower affinity) suggests that animals of small size with high metabolic rate (high arteriovenous oxygen difference) living in normoxic or possibly exposed to moderately hypoxic condition only are better served by a relatively low oxygen affinity whereas animals native to high altitude are better adapted to severe hypoxia when having a high oxygen affinity.

Variability of intercapillary distance estimated on histological sections of rat heart.

The majority of models of O2 supply to myocardial tissue are based on the classical model of Krogh (1919). This model requires the radius of the tissue cylinder as one of the crucial input data. Usually, only its mean value has been considered, as derived on histological sections from the number of capillaries per mm2. However, for a realistic description, the full distribution of the radii of the tissue cylinders has to be taken into account. Recently this distribution was shown to be approximately log-normal (Renkin et al., 1981; Turek and Rakusan, 1981), and thus to be fully defined by median radius and logarithmic standard deviation (log SD), the latter serving as an index of the variability.

Cardiac hypertrophy, capillary and muscle fiber density, muscle fiber diameter, capillary radius and diffusion distance in the myocardium of growing rats adapted to a simulated altitude of 3500 m.

SummaryIn growing rats adapted to a simulated altitude of 3500 m for about 4 weeks and in their controls the evolution of cardiac ventricular weight was followed. The increase of total ventricular weight found in the adapted animals can be attributed exclusively to the increase of right ventricular weight. In other adapted and control animals cardiac capillary densities, muscle fiber diameter and external capillary radius were estimated and fiber—capillary ratio and diffusion distance were calculated. There was an increase of capillary density together with a decrease of muscle fiber density, fiber-capillary ratio and diffusion distance in the right but not in the left ventricle of the adapted rats. The muscle fiber diameters, however, were larger in both heart ventricles of the rats exposed to a simulated high altitude, especially in the right ventricle. This indicates that true hypertrophy of the muscle fibers is mainly responsible for the increase of right ventricular weight. In the left ventricle, however, a hypertrophy of the muscle fibers together with a decrease of stroma components is demonstrated. The physiological importance of the shorter diffusion distance in the right ventricle of the high altitude adapted rats is discussed and it is suggested that the shorter diffusion distance may help to keep the tissue O2 partial pressure above the critical value, mainly also in extreme situations with high myocardial O2 consumption.

Lognormal distribution of intercapillary distance in normal and hypertrophic rat heart as estimated by the method of concentric circles: its effect on tissue oxygenation

The inhomogeneity of the capillary net in the cardiac muscle was estimated using our morphometric measurements in normal and hypertrophic rats hearts. As entry data we used the distribution of tissue at different distances from the nearest capillary as measured by the method of concentric circles and the mean intercapillary distance independently calculated from the capillary density. The derived distribution of intercapillary distances was approximated by lognormal distribution in which the spread can be characterized by a single parameter, namely the log standard deviation.The effect of the log standard deviation on tissue oxygenation was evaluated in normal and hypertrophic hearts, at normoxia and at hypoxia. The mean tissuePO2 and the percentage of anoxic tissue at the venous end of the tissue cylinder were calculated using Kroghs model. Two boundary situations were considered: A) the end-capillaryPO2 was assumed to be equal in all capillaries due to compensatory adjustment in blood flow; B) the same flow in all capillaries was assumed resulting in varying end-capillaryPO2. The real situation is expected to be between situations A and B. Increased variability of intercapillary distance proved to impair considerably the tissue oxygenation, especially when the results were expressed as a percentage of anoxic tissue. The percentage of anoxic tissue turned out to be a better index of tissue oxygenation than the meanPO2 particularly at hypoxia. The results suggest the presence of at least a partial adjustment of blood flow with respect to the width of tissue cylinder. Without such adjustment, a large part of tissue would become anoxic already in normal hearts at normoxia and this would be further aggravated by hypertrophy and/or hypoxia.

Blood gases at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve.

AbstractTheoretical 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

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

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Blood O2 content, cardiac output, and flow to organs at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve

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