Duration of blood flow reduction to normal liver tissue induced by angiotensin, vasopressin and endothelin. 1994

T W Hennigan, and T G Allen-Mersh
Department of Surgery, Chelsea and Westminster Hospital, London, UK.

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D010478 Chemotherapy, Cancer, Regional Perfusion Neoplasm drug therapy involving an extracorporeal circuit with temporary exclusion of the tumor-bearing area from the general circulation during which high concentrations of the drug are perfused to the isolated part. Cancer Chemotherapy, Regional Perfusion,Perfusion Cancer Chemotherapy, Regional,Regional Perfusion Antineoplastic Chemotherapy,Isolation Perfusion Cancer Chemotherapy,Regional Perfusion Cancer Chemotherapy
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014667 Vasopressins Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure. Antidiuretic Hormone,Antidiuretic Hormones,beta-Hypophamine,Pitressin,Vasopressin,Vasopressin (USP),Hormone, Antidiuretic,beta Hypophamine
D016232 Endothelins 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides. Endothelium-Derived Vasoconstrictor Factors,Endothelin,Vasoconstrictor Factors, Endothelium-Derived
D017078 Laser-Doppler Flowmetry A method of non-invasive, continuous measurement of MICROCIRCULATION. The technique is based on the values of the DOPPLER EFFECT of low-power laser light scattered randomly by static structures and moving tissue particulates. Doppler-Laser Flowmetry,Flowmetry, Laser-Doppler,Laser-Doppler Velocimetry,Velocimetry, Laser-Doppler,Doppler Laser Flowmetry,Flowmetry, Doppler-Laser,Flowmetry, Laser Doppler,Laser Doppler Flowmetry,Laser Doppler Velocimetry,Velocimetry, Laser Doppler

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