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Titolo:
Pharmacological regulation of postischemic sinusoidal diameters in rats - A new approach for reducing hepatic ischemia/reperfusion injury
Autore:
Uhlmann, D; Uhlmann, S; Loffler, BM; Witzigmann, H; Spiegel, HU;
Indirizzi:
Univ Leipzig, Dept Surg 2, D-04103 Leipzig, Germany Univ Leipzig LeipzigGermany D-04103 pt Surg 2, D-04103 Leipzig, Germany Univ Leipzig, Dept Ophthalmol, D-04103 Leipzig, Germany Univ Leipzig Leipzig Germany D-04103 phthalmol, D-04103 Leipzig, Germany F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland F Hoffmann La Roche & Co Ltd Basel Switzerland CH-4002 asel, Switzerland Univ Munster, Dept Gen Surg Surg Res, D-4400 Munster, Germany Univ Munster Munster Germany D-4400 rg Surg Res, D-4400 Munster, Germany
Titolo Testata:
CLINICAL HEMORHEOLOGY AND MICROCIRCULATION
fascicolo: 4, volume: 24, anno: 2001,
pagine: 233 - 246
SICI:
1386-0291(2001)24:4<233:PROPSD>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
ISCHEMIA-REPERFUSION INJURY; ENDOTHELIN RECEPTOR ANTAGONIST; NITRIC-OXIDE; LIVER-TRANSPLANTATION; LEUKOCYTE ADHESION; CELL CONTRACTION; STELLATE CELLS; WARM ISCHEMIA; IN-VIVO; MICROCIRCULATION;
Keywords:
liver; ischemia/reperfusion; microcirculation; vasoregulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Uhlmann, D Univ Leipzig, Dept Surg 2, Liebigstr 20A, D-04103 Leipzig, Germany Univ Leipzig Liebigstr 20A Leipzig Germany D-04103 ig, Germany
Citazione:
D. Uhlmann et al., "Pharmacological regulation of postischemic sinusoidal diameters in rats - A new approach for reducing hepatic ischemia/reperfusion injury", CL HEMORH M, 24(4), 2001, pp. 233-246

Abstract

Ischemia leads to profound endothelin-related constriction of the hepatic microcirculation with resulting disturbances in blood and oxygen supply. The aim of the study was to modulate hepatic microvascular diameters by blocking endothelin receptors with bosentan, and also to find the best possible vessel width (as produced by bosentan) for minimizing ischemia/reperfusion injury. Methods: In an in vivo rat model hepatic ischemia was induced for 30 minutes by crossclamping the hepatoduodenal ligament. The endothelin receptor antagonist (ERA) bosentan was administered before ischemia in stepwise dosages of 0.1, 1.0 and 10 mg/kg bw i.v. and 10 mg/kg bw intraportally (i.p.). Vasoactive effect was assessed by in vivo microscopy. The influence on hepatic oxygen supply and hepatocellular function was evaluated by measuring local tissue pO(2) and AST levels. Results: Because of ischemia sinusoidal diameters were reduced to 76.3 +/-7.4% compared with values found in sham-operated animals. After administration of 0.1 mg/kg ERA (bosentan) the sinusoids remained constricted (89.7 +/-9.9%). Blocking endothelin receptors with 1 mg/kg bosentan avoided sinusoidal constriction (99.0 +/-8.8%, p<0.05) and led to the most effective reduction of AST level peak after 6 h of reperfusion (244.0<plus/minus>34.2 U/l vs 422.9 +/- 163.3 U/l in untreated ischemia). 10 mg/kg i.v. caused an increase in sinusoidal diameter to 109.1 +/-6.4% and 10 mg/kg intraportally to 136.8 +/- 19.3% and even an increase in AST levels (618.9 +/- 209.3 U/l). Hepatic ischemia led to a significant decrease of local tissue pO2 after reperfusion (9.4 +/-1.2 mm Hg; p<0.05 vs sham: 16.8<plus/minus>1.8 mm Hg). Thegreatest improvement in postischemic oxygen supply was found in the 1.0 mg/kg group (12.9 +/-1.0 mm Hg; p<0.05 vs ischemia). Venular diameter changedalmost to the same extent as sinusoidal diameter. Perfusion rate was significantly increased and sticking of leukocytes in sinusoids; and venules; was reduced after doses of 1 and 10 mg/kg bw bosentan i.v. (p<0.05). Implications: In this model we were able to regulate the diameters of sinusoids and postsinusoidal venules incrementally. We conclude that the avoidance of constriction, without excessive vasodilatation gives increased perfusion rates with improved hepatic oxygen supply and hepatocellular function.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/01/20 alle ore 18:55:01