ENDOLYMPHATIC APPLICATION OF BLEOMYCIN OIL SUSPENSION IN DOG MODEL

Abstract

To explore the potential usefulness of a cytostatic
agent deposited directly in lymph nodes, 4ml
Bleomycin oil suspension (Oil-Bleo) was injected over
one hour into hind leg lymphatics of seven dogs. Five
of these dogs received a second, identical dose one
week later into lymphatics of the contralateral hind
leg.
Peak serum concentration of Oil-Bleo after the
first injection (7 dogs) was 12.3 g/ml but after the
second injection (5 dogs) was slightly lower (10.8
g/ml). Maximum level of Oil-Bleo in blood was
12% of the endolymphatic dose and represented the
"spillover" from lymph transport. In a control experiment,
in which 60mg of aqueous Bleomycin was
injected, the serum spillover was one-third higher.
Large amounts of Oil-Bleo were stored in
popliteal and retroperitoneal lymph nodes for several
weeks. Twenty-four hours after injection the weight
of "treated" lymph nodes was 73% greater than
"untreated" nodes and one month later treated
lymph nodes were still 37% heavier. After 24 hours,
4.7% of Oil-Bleo instilled was distributed within extracted
lymph nodes, and one month later 0.12%
was still detectable. By contrast, after aqueous
Bleomycin infusion, only 0.05% was detected in
these lymph nodes after only six hours. In general,
lymph nodal architecture was preserved after OilBleo.
Together the findings suggest that Bleomycin
oil suspension may be a useful agent for treatment of
lymph nodal metastases by endolymphatic infusion.