European Journal of Nuclear Medicine Original article Kinetics of heat-damaged homologous erythrocytes A five-compartmental analysis Panagiotis A. Dimitriou, Alfred K. Depascouale, Anastasios E. Germenis, and Spiros-Emilios P. Antipas Laboratory of Nuclear Medicine, Department of Pathologic Physiology, University of Athens, GR-115 27 Athens, Greece Received August 16, 1989 and in revised form December 6, 1989 Abstract. A new theoretical five-compartmental model (5CM) was developed for analysis of the clearance of heat-damaged erythroctes (HDE) labelled with chromi- um 51. Besides the HDE-spleen interaction, this new model also takes into account the interaction between extrasplenic reticuloendothelial (RES) sites and HDE, i.e. the hepatic clearance of fragmented erythrocytes (FE). Accordingly, HDE clearance curves are analysed into three exponential components, the fastest of which describes the RES-FE interaction, whereas the others describe the splenic clearance of spherocytes. Therefore, an estimation of the effective liver blood flow for HDE (ELBF) was achieved, along with a series of parameters describing splenic function. The 5CM proved to be more efficient than a previously proposed three-compartmen- tal model (3CM) in the mathematical description of HDE clearance. Comparison was made by applying both models to 37 experimental curves obtained from 20 patients with congenital hemolytic anemias. The values for the splenic function parameters calculated by 5CM analysis and the strong correlations observed among them offer evidence that this model provides an adequate approximation to the real conditions under which HDE clearance takes place. Furthermore, a de- tailed quantitative analysis of the pooling of spherocytes within the spleen was attempted in this work, and this phenomenon was found to compete with splenic irrevers- ible spherocyte trapping. The ELBF proved to be closely correlated with the hemodynamic splenic parameters, following first-order kinetics, as do low-dose colloids. Key words: Heat-damaged erythrocyte kinetics Spleen blood flow - Splenic pooling - Effective liver blood flow Eur J Nucl Med (1990) 17:49-54 Offprint requests to: P. Dimitriou Introduction In the early 1980s, Peters et al. (1981) presented a three- compartmental model (3CM) for the analysis of the ki- netics of heat-damaged erythrocytes (HDE). According to that model, the HDE clearance curve is analysed into two exponential components, resulting in the estimation of a series of parameters of splenic function, such as spleen blood flow (SBF), irreversible HDE splenic up- take, the transient time of reversibly trapped HDE, and the splenic extraction ratio for HDE. Furthermore, that work underlined the significant role played by cell pool- ing within the spleen in HDE kinetics. A disadvantage of the 3CM is that it does not con- front theoretically the well-known interaction of HDE with extrasplenic reticuloendothelial (RES) sites. By sur- face counting studies, it was documented that a propor- tion of HDE is taken up by the liver and that this phe- nomenon is completed within 10 rain after HDE injec- tion (Kimber and Lander 1964; Peters et al. 1982). To avoid the influence of this interaction on the values of the parameters derived from the 3CM, Peters et al. (1981) processed the experimental curves starting from the point of 8 min postinjection, applying to the calcula- tions the 3-rain instead of zero time intercepts of the two exponential lines. In our experimence (Germenis et al. 1986, 1988), the absence of a theoretical approach to the RES-HDE interaction in the 3CM causes practical problems in its use, inducing an unpredictable error of estimation for the parametric values obtained. In the present work, an attempt was made to improve the analysis of Peters et al. (1981), giving due considera- tion to the RES-HDE interaction. For this purpose, a new five-compartmental model (5CM) was designed, the efficacy of which was controlled using 37 HDE clearance curves previously recorded in our laboratory. Based on this model, a detailed quantitative estimation of the splenic pooling of HDE was also achieved. © Springer-Verlag 1990