Segmental liver IRI in rat, what role does NO play? | Application
Segmental liver IRI in rat, what role does NO play?
Registration number: LIO-13838
Kliniskt forskningsprojekt för ST-läkare vid Landstinget i Östergötland
Application started by: Bergthor Björnsson, 2008-03-27
Professional title at the time of application: Läkare
Work place at the time of application: Kirurgkliniken US
Last updated / corrected by: ST-kansliet Beslut, 2008-09-23
Application received by: Region Östergötland
RejectedRejected
Applicant: Bergthor Björnsson
Kirurg, Kirurgkliniken US

Information

Ämnesområde

Biokemisk struktur och metabolism

Sammanfattning av projektet

The Pringle’s manover is often used during major liver resections to minimize intraoperative bleeding. The duration of ischemia can effect the liver’s ability to regenerate postoperatively. The ischemia is thought to induce apoptosis but the reperfusion causes cell injury via oxidative stress. Apoptosis and reperfusion injury can play role in postopertive complications and liver failure. However the precise mechanisms leading to the damage have not been elucidated. One of the important mechanisms could be sinusoidal endothelial cell damage leading to microcirculatory dysfunction. This may be related to NO. NO derived from eNOS is thought to counteract vasoconstriction in the sinusoids and thus improve circulation. NO is even able to minimize adhesions between neutrophils and endothelial cells as well as prevent platelet aggregation. In addition NO inhibits superoxide anion production by neutrophils and removes superoxides. However NO produced by iNOS in greatly increased amount under IRI might have toxic effect via oxidative damage. To day no study has shown direct how NO amount changes in the liver under ischemia / reperfusion.
Microdialysis(MD) makes it possible to measure changes in tissue before any signs can be found in the circulation. With laser doppler it is possible to measure local blood flow in tissue such as the liver.
Animals are randomly allocated into four groups; 1) Control operated but no ischemia 2) Only ischemia 3) Ischemia and 3 hours reperfusion and 4) Ischemia and 6 hours reperfusion. Biopsies are taken from the livers in group 1) at the end of ischemia, after 3 and 6 hours of reperfusion. From group 2 the samples are taken at the end of 60 min ischemia. From group 3 and 4 the samples are taken at 3 and 6 hours reperfusion respectively.
In MD samples glucose, lactate, pyruvate and glycerol as well as NOx is measured.
In blood liver function tests and NOx
The liver tissue is harvested and stained for histology and eNOS/iNOS.

Doktorandanmäld

not checked Ja
checked Nej

Halvtidskontroll

not checked Ja
checked Nej

Disputerad

not checked Ja
not checked Nej

Docent

not checked Ja
checked Nej

Medarbetare/handledare

Per Sandström
Överläkare, Centrum för Kirurgi, Ortopedi och Cancervård
Anders Winbladh
Överläkare, Centrum för Kirurgi, Ortopedi och Cancervård
Lena Trulsson
Forskarassistent, Klinisk experimentell forskning / Kirurgiska kliniken i Östergötland

Supervisor

Per Gullstrand
Docent, överläkare, Närsjukvården i Centrala Östergötland

Forskningsmeriter

Publikationslista är inlagd/uppdaterad i ansökningssystemets personkort

checked Ja
not checked Nej

Forskningsmeriter (beskriv här eventuella tidigare forskningserfarenheter samt relevanta utbildningsmoment, utmärkelser m m)

In addition to the list presented in the CV I participate in a study called "Effekt av acetylcystein in vivo vid segmentell ischemi-reperfusionsskada i grismodell" together with my coworkers in the present study. In the near future I will start my formal PhD education in the field of liver ischemia and reperfusion injury.

Forskningstid

Forskningstid önskas för följande antal månader (1-3 månader kan sökas)

3

Tidplan för uttag av forskningstid

 ÅrMånadAktivitet
Forskningstid2009Mars - part timePart one of operations
Forskningstid2009April - part timePart one of operations
Forskningstid2009Juni - part timeAnalysis of MD and blood samples
Forskningstid2009Agust - part timeHistology + article writing
Forskningstid   

Decision

Decision date: 2008-09-24


Segmental liver IRI in rat, what role does NO play? | Application, from Region Östergötland
http://researchweb.org/is/en/lio/ansokan/13838