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

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.