Document Detail


Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation.
MedLine Citation:
PMID:  18056916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Arterial hypertension (HT) has been reported in all studies involving bevacizumab, an antiangiogenic agent designed to target vascular endothelial growth factor (VEGF). The mechanism underlying bevacizumab-related HT is not yet clearly understood. As far as endothelial dysfunction and microvascular rarefaction are hallmarks in all forms of HT, we tested the hypothesis that anti-VEGF therapy could alter the microcirculation in nontumor tissues and, thus, result in an increase in blood pressure (BP). We used intravital video microscopy to measure dermal capillary densities in the dorsum of the fingers. Microvascular endothelial function was assessed by laser Doppler flowmetry combined with iontophoresis of pilocarpine (acetylcholine analogue). All measurements were carried out in 18 patients before and after a 6-month treatment with bevacizumab (mean cumulative dose: 3.16 +/- 0.90 g). Mean BP was increased after 6 months of therapy compared with baseline, from 129 +/- 13/75 +/- 7 mmHg to 145 +/- 17/82 +/- 7 mmHg for systolic BP and diastolic BP, respectively (P < 0.0001). Compared with the baseline, mean dermal capillary density at 6 months was significantly lower (75 +/- 12 versus 83 +/- 13/mm(2); P < 0.0001), as well as pilocarpine-induced vasodilation (P < 0.05). Thus, bevacizumab treatment resulted in endothelial dysfunction and capillary rarefaction; both changes are closely associated and could be responsible for the rise in BP observed in most patients.
Authors:
J-J Mourad; G des Guetz; H Debbabi; B I Levy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-04
Journal Detail:
Title:  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO     Volume:  19     ISSN:  1569-8041     ISO Abbreviation:  Ann. Oncol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-29     Completed Date:  2008-06-24     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  9007735     Medline TA:  Ann Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  927-34     Citation Subset:  IM    
Affiliation:
Avicenne Hospital Assistance Publique-Hôpitaux de Paris, Paris XIII University (EA3412), Bobigny, France.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / blood supply,  drug therapy,  secondary
Aged
Angiogenesis Inhibitors / adverse effects*,  pharmacology,  therapeutic use
Antibodies, Monoclonal / adverse effects*,  pharmacology,  therapeutic use
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Blood Pressure / drug effects*
Capillaries / drug effects
Cholinergic Agents / administration & dosage,  pharmacology
Colorectal Neoplasms / blood supply,  drug therapy
Diabetes Mellitus, Type 2 / complications,  physiopathology
Endothelium, Vascular / drug effects,  physiopathology
Female
Fingers / blood supply
Forearm / blood supply
Humans
Hypertension / chemically induced*
Iontophoresis
Laser-Doppler Flowmetry
Male
Microcirculation / drug effects*
Microscopy, Video
Middle Aged
Neovascularization, Pathologic / drug therapy*
Pilocarpine / administration & dosage,  pharmacology
Vasodilation / drug effects
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Cholinergic Agents; 2S9ZZM9Q9V/bevacizumab; 92-13-7/Pilocarpine

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