Duration of blood flow reduction to normal liver tissue induced by angiotensin, vasopressin and endothelin.
Cytotoxic drug uptake into tumour tissue depends on blood flow. Flow can be diverted to tumour by vasoconstrictors but the effect is temporary whereas prolonged exposure is required. The relative drug uptake advantage depends on the relative tumour blood flow compared to normal tissue. Blood flow to normal liver therefore is an important factor in dose-limiting uptake into normal tissue. Regional drug infusion must match vasoconstrictor action. This was measured by laser doppler flowmetry. The median duration of action was 4.2 minutes for angiotensin, 8.6 for vasopressin and 20.7 for endothelin. Therefore the cytotoxic agent could be infused for the same period repeatedly to reduce toxicity. The flux fall was 33% for angiotensin, 22% for vasopressin and 16% for endothelin. The area below the flux line was 104% minutes for angiotensin, 193% for vasopressin and 335% for endothelin. To increase cytotoxic drug uptake, the cytotoxic drug infusion should be infused intermittently for the duration that the vasoconstrictor is active. As the area under the curve is greatest for endothelin this may be the agent of choice.
Hennigan
T W
TW
Department of Surgery, Chelsea and Westminster Hospital, London, UK.
Allen-Mersh
T G
TG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D016232:Endothelins / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000098:blood supply*; D008297:Male; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016232:Endothelins; D014667:Vasopressins; D000804:Angiotensin II