Endogenous Production of ¹⁴CO: A Method for Calculation of RBC Life-span In Vivo

A kinetic model is presented for estimation of the degradation rate of labeled heme by measurement of appearance of ¹⁴CO in the breath following injection of glycine-2-¹⁴C. This method does not require sampling of blood or other body fluids, is absolutely independent of circulating blood volume and relatively independent of erythropoietic rate, and estimates the relative contribution to ¹⁴CO production from destruction of circulating RBC hemoglobin heme and that arising from other heme sources. For circulating RBC, rate of random hemolysis, mean potential lifespan and spread of lifespans about this mean can be calculated. Mean overall RBC lifespan and the fraction of RBC dying of senescence can be derived from these calculations. In normal male buffalo rats, the average value for random hemolysis was 0.67 per cent per day, corrected mean potential lifespan 66.2 days and standard deviation about this mean of 7.6 days. For normal female LAF₁ mice, the corresponding average values were 0.60, 51.8 and 9.1, respectively. Results in two other inbred mouse strains were similar save for a shorter mean potential lifespan of 47.1 days in SEC/1Re mice and a longer mean potential lifespan of 57.3 days in WC-B6 mice. Following splenectomy in the rat, an isolated significant increase in mean potential lifespan was seen. An isolated decrease in mean potential lifespan was seen in three rats recovering from phenylhydrazine-induced anemia. An example of markedly increased random hemolysis, together with shortened mean potential life-span, was seen in a gastrectomized rat with a severe hypochromic anemia. The present method is shown to simultaneously determine the major parameters defining RBC survival, and as such, should be quite useful in the study of red blood cell disorders in animals and man.