Rl. Scipioni et al., CLINICAL AND CLINICOPATHOLOGICAL ASSESSMENT OF SERIAL PHLEBOTOMY IN THE SPRAGUE-DAWLEY RAT, Laboratory animal science, 47(3), 1997, pp. 293-299
Two studies, designed to mimic a single-dose, cross-over pharmacokinet
ic protocol, were conducted to gain a better understanding of the rat'
s response to multiple, frequent blood sampling. Parameters evaluated
included body weight, clinical signs of disease, hematologic and serum
biochemical analytes, organ weights, and histopathologic features. St
udy groups consisted of either 6 or 8 male, viral antibody-free, Sprag
ue Dawley rats. These included controls and blood-collection groups th
at represented withdrawal of 10, 15, 20, 30, and 40% of estimated tota
l blood volume. Volume of blood collected per time point was based on
the total volume to be withdrawn divided by the 13 samples that were c
ollected over 24 h. This regimen was repeated 2 weeks later. Samples w
ere taken for clinical pathologic evaluation on the days subsequent to
blood collection for both studies as follows: 0, 1, 2, and 3 days; 7,
8, or 9 days; and either 13 or 14 days. In Study 1, samples were also
taken on either days 15 or 16, and on 17 or 18 after the second blood
collection. Approximately 2 weeks after the second blood collection r
egimen, animals were euthanized. Animals in one study were necropsied,
and selected tissues were taken for histologic examination. Analysis
of variance, based on changes from baseline, was used to assess group
differences, Results indicate that the rate of body-weight gain for th
e bled groups was not significantly different from that of the control
s. Group differences in multiple hematologic parameters were significa
nt. Changes mere typical of acute blood-loss anemia, with positive or
negative trends relating to the volume of blood removed. In addition,
these changes were characterized by recovery to control values within
approximately 14 days. Few statistically significant group differences
were detected in serum biochemical values, and those detected were no
t biologically relevant. Although organ weights of bled groups were si
milar to those of controls, minimal to mild splenic hematopoiesis was
present in all bled groups, compared with controls. These data indicat
e that removal of up to 40% of a rat's total blood volume over a 24-h
period, and repeated 2 weeks later, caused no gross ill effects.