Blood flow in liver tumors--effects of vasoactive drugs estimated with xenon (133Xe) clearance.
OBJECTIVE
The aim of the present study was to identify in a standardized experimental rat liver tumor system the drugs which are most appropriate in influencing the relationship between liver tumor and normal liver parenchyma blood flow as estimated with 133Xe washout clearance method, and thereby positively influencing the kinetics of chemotherapeutic drugs. A battery of vasoactive drugs, which according to a literature review were considered to be active, were tested.


METHODS
Twelve drugs were administered intravenously on 113 Wistar-Fu rats with an experimental adenocarcinoma in the liver (weight 0.62 g). 133Xe was applied in the tumor and in normal parenchyma with and without administration of a vasoactive drug. The pulses were registered with a NaI (Tl)-scintillation detector connected to a multichannel analyzer. The disappearance rate of the isotope was calculated according to a single compartment model. Four recordings were performed in each rat randomly in tumor and liver parenchyma with and without a drug (series A) and one series twice in tumor and twice in parenchyma with a drug (series B).


RESULTS
In unaffected animals the tumor to liver quotient was 0.57+/-0.35. This quotient was higher in tumors less than 0.53 g. Angiotensin-II 8 mg i.v. increased the quotient to 0.95+/-0.20. No other drug significantly influenced the quotient.


CONCLUSIONS
In an experimental adenocarcinoma in the liver this study has investigated the possibility of increasing the tumor to normal liver parenchyma blood flow quotient by a variety of vasoactive substances for the beneficial modification of tumor blood flow. Angiotensin II 8 mg i.v. was the only drug, which increased the quotient. None of the other tested drugs were supporting previous presented results on influencing tumor blood flow.
Lindnér
P
P
Department of Clinical Physiology, Sunderby Hospital, Luleå, Sweden.
Tölli
J
J
Naredi
P
P
Oman
M
M
Hafström
L
L
D000818:Animals; D008113:Liver Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014980:Xenon Radioisotopes / Q000493:pharmacokinetics*
D014662:Vasoconstrictor Agents; D014980:Xenon Radioisotopes