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Titolo:
VERAPAMIL-REVERSING CONCENTRATIONS INDUCE BLOOD-FLOW CHANGES THAT COULD COUNTERACT IN-VIVO THE MDR-1-MODULATING EFFECTS
Autore:
RAMIREZ LH; MUNCK JN; ZHAO ZX; BOGNEL C; RICARD M; ARDOUIN P; ROUGIER P; GOUYETTE A;
Indirizzi:
INST GUSTAVE ROUSSY,DEPT MED,39 RUE CAMILLE DESMOULINS F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT MED F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT ANATOMOPATHOL VILLEJUIF FRANCE INST GUSTAVE ROUSSY,SERV EXPTL ANIM VILLEJUIF FRANCE INST GUSTAVE ROUSSY,PHARMACOL CLIN LAB,SERV PHYS VILLEJUIF FRANCE INST GUSTAVE ROUSSY,CNRS,URA 147 VILLEJUIF FRANCE
Titolo Testata:
Cancer
fascicolo: 3, volume: 74, anno: 1994,
pagine: 810 - 816
SICI:
0008-543X(1994)74:3<810:VCIBCT>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEPATIC-ARTERY INFUSION; HIGH-DOSE VERAPAMIL; MULTIDRUG-RESISTANCE; PHASE-I; CELL LINES; DOXORUBICIN; TUMORS; CYCLOSPORINE; VINBLASTINE; ENHANCEMENT;
Keywords:
VERAPAMIL; DOXORUBICIN; HEPATIC ARTERY INFUSIONS; VX2 TUMOR; DRUG RESISTANCE; HEPATIC BLOOD FLOW;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
L.H. Ramirez et al., "VERAPAMIL-REVERSING CONCENTRATIONS INDUCE BLOOD-FLOW CHANGES THAT COULD COUNTERACT IN-VIVO THE MDR-1-MODULATING EFFECTS", Cancer, 74(3), 1994, pp. 810-816

Abstract

Background. Intraarterial hepatic (IAH) administration of verapamil should achieve mdr-1-reversing concentrations with reduced cardiac toxicity. The authors have explored the tolerance of its IAH administration and its effects on doxorubicin pharmacodynamics. Methods. Verapamil was given to rabbits by intravenous or IAH administration, and its effects on heart rates were compared. Doxorubicin then was given intravenously either with IAH verapamil or with an IAH control perfusion, and tumor and liver drug concentrations were determined. Hepatic blood flow changes were studied by the administration of Tc-99m-albumin macroaggregates (Tc-99m-MAA) under verapamil IAH perfusions. Results. Compared with the intravenous route, IAH administration of verapamil was not toxic, and cardiac effects were reduced significantly. Its effect on doxorubicin distribution was detrimental, because the tumor-liver doxorubicin concentration ratios were lower in the verapamil group (0.23 vs. 3.37; P < 0.05). Tumor doxorubicin concentrations were lower when verapamil was coinfused (43 vs. 573 ng/100 mg tissue; P < 0.05). In normal liver tissue, increased amounts of doxorubicin and metabolites wereobserved. The verapamil IAH perfusions with Tc-99m-MAA confirmed a differential action on tumor and normal vessels; the distribution of radionuclide was diverted away from the tumor bed significantly when verapamil was administered (tumor-to-liver ratio of 25.3 control rabbits vs. 5.99 rabbits who received verapamil; P < 0.05). Conclusions. Reversing the concentrations of verapamil provoked changes in the distribution of the liver blood flow. The hemodynamic effects of verapamil regional perfusions could counteract in vivo its potential mdr-1-reversing properties.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 04:41:37