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Titolo:
Prevention and reversal of experimental posthemorrhagic vasospasm by the periadventitial administration of nitric oxide from a controlled-release polymer
Autore:
Tierney, TS; Clatterbuck, RE; Lawson, C; Thai, QA; Rhines, LD; Tamargo, RJ;
Indirizzi:
Johns Hopkins Univ, Sch Med, Dept Neurol Surg, Baltimore, MD USA Johns Hopkins Univ Baltimore MD USA Dept Neurol Surg, Baltimore, MD USA
Titolo Testata:
NEUROSURGERY
fascicolo: 4, volume: 49, anno: 2001,
pagine: 945 - 951
SICI:
0148-396X(200110)49:4<945:PAROEP>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANEURYSMAL SUBARACHNOID HEMORRHAGE; INTRAARTERIAL PAPAVERINE INFUSION; INTERCELLULAR-ADHESION MOLECULE-1; ENDOTHELIUM-DEPENDENT RELAXATION; PLACEBO-CONTROLLED TRIAL; CEREBRAL ARTERIAL SPASM; RABBIT BASILAR ARTERY; POLYMORPHONUCLEAR LEUKOCYTES; CEREBROSPINAL-FLUID; DRUG-DELIVERY;
Keywords:
(Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate; controlled release; ethylene/vinyl acetate polymer; nitric oxide; subarachnoid hemorrhage; vasospasm;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
74
Recensione:
Indirizzi per estratti:
Indirizzo: Tamargo, RJ Johns Hopkins Univ Hosp, Meyer 7-113,600 N Wolfe St, Baltimore, MD 21287 USA Johns Hopkins Univ Hosp Meyer 7-113,600 N Wolfe St BaltimoreMD USA 21287
Citazione:
T.S. Tierney et al., "Prevention and reversal of experimental posthemorrhagic vasospasm by the periadventitial administration of nitric oxide from a controlled-release polymer", NEUROSURGER, 49(4), 2001, pp. 945-951

Abstract

OBJECTIVE: Despite improvements in the care of patients with aneurysmal subarachnoid hemorrhage, delayed cerebral vasospasm remains a major cause of morbidity and death. There is now evidence that a decrease in the local availability of nitric oxide (NO) plays a role in delayed cerebral vasospasm. We evaluated a controlled-release polymer containing the NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO) for the treatment of chronic posthemorrhagic vasospasm in the rat femoral artery model. METHODS: The release kinetics of ethylene/vinyl acetate copolymers loaded with 20% (w/w) DETA/NO were determined in vitro. Chronic vasospasm was induced in the left femoral artery of adult male Fischer 344 rats (n = 35) by exposure to autologous blood. At 1, 3, or 7 days after blood exposure, either a 5-mg polymer loaded with 20% (w/w) DETA/NO or an empty 5-mg polymer wasplaced in the periadventitial space next to the left femoral artery. At the same time, an empty 5-mg polymer was placed next to the right femoral artery. On the 8th day after blood exposure (at the peak of vasospasm in this model), rats were transcardially perfused with 4% paraformaldehyde, and theleft and right femoral arteries were removed for histological processing and morphometric analyses. Vasospasm was expressed as the percent lumen patency of the treated left artery, compared with the control right artery. RESLTS: The in vitro release kinetics demonstrated that the 20% DETA/NO-loaded polymers released up to 15% of their total drug load during a 9-day period. DETA/NO treatments initiated at 1, 3, or 7 days after blood deposition all significantly inhibited vasospasm, compared with control values (94.6+/- 7.2% versus 67.6 +/- 5.8%, 104.6 +/- 5.5% versus 64.9 +/- 1.7%, and 102.4 +/- 5.1% versus 73.6 +/- 1.4%, respectively; mean standard error of themean percent lumen patency; P < 0.001). No adverse effects of treatment were observed. CONCLUSION: The diazeniumdiolate NO donor DETA/NO can be effectively released from ethylene/vinyl acetate polymers. Administration of DETA/NO into the periadventitial space can prevent the development of chronic posthemorrhagic vasospasm in the rat femoral artery and can reverse established vasospasm. No adverse effects of DETA/NO were observed in this model.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 07:40:21