EFFECT OF COMBELEN(R) ON THE DISTRIBUTION OF ERYTHROCYTES IN THE DOG

The effect of Combelen(R) (3.9 mg/kg bw s.c.) on the distribution of e rythrocytes in dogs was investigated. After application of Combelen(R) , the hematocrit of the animals decreased exponentially within 1 h by 21 %. The reversal of the reduction began from 2 h after the time of a pplication, amounting to 4% within the first day and finishing by the fourth day. After injection of Cr-51-labelled erythrocytes, radioactiv ity in the circulation of Combelen(R)-treated dogs decreased exponenti ally within 2 h by at least 30 %. It was concluded that the dog's sple en, under physiological conditions, contains about 10 % of the animal' s blood. The time-courses of the decrease of hematocrit and radioactiv ity in the circulation were found to be very similar. In accordance wi th this observation, a high correlation (r = 0.97) between the level o f radioactivity after injection of radio-labelled erythrocytes and the corresponding hematocrit values after application of Combelen(R) was found. After application of erythrocytes, labelled with 99mTc, an exte nsive distribution from the circulation into the spleen was observed b y scintigraphy. This process can be understood by using a closed-compa rtment model. An equation, based on this model, describes the observed time course of the hematocrit values, as well as the number of Cr-51- labelled erythrocytes, in Combelen(R)-treated dog. Presumably, the obs erved effect of Combelen(R) is the result of the relaxation of the smo oth muscle cells in the trabeculae of the spleen, caused by central-ne rvous depression of sympathetic tone. Combelen(R) seems to be a suitab le tool in pre-clinical testing of novel blood preserve with dog as a test animal. Its potent ability to eliminate erythrocytes from circula tion is distinguishable from the sequestration of damaged red cells. F urthermore, its ability to prevent the spleen from uncontrolled hemato critmodulating actions in addition to its sedative effects is consider ed to be an invaluable advantage.