L-arginine, a precursor of NO, reduces ischemia-reperfusion injury and increases microcirculatory bloodflow. This will lead to a reduction of complications in free flap surgery.
ID
Bron
Verkorte titel
Aandoening
reperfusion injury, Arginine, free flap surgery
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
Partial flap loss (result of insufficient bloodflow).
Achtergrond van het onderzoek
Partial flap loss due to microvascular failure is first initiated by the incapability of the vascular pedicle to provide sufficient microvascular perfusion in distal segments of the flap. In addition, in free flap surgery the entire flap is affected by ischemia reperfusion injury. The distal segments in free flap surgery are particular vulnerable for ischemia reperfusion injury, and are thus primarily affected by ischemia reperfusion injury which may lead to distal partial flap loss.
Nitric oxide (NO) has been the focus in an extensively amount of studies regarding its use in reducing the IR-injury. It is widely accepted that the L-Arginine-Nitric Oxide pathway plays a pivotal role in the pathophysiology of IR-injury. L-Arginine, the sole precursor of NO, can be metabolized in NO and citruline by a family of tree isoforms of NO synthase (NOS). Endothelial NOS (eNOS) and neuronal NOS (nNOS), these are mainly constitutively expressed by respectively endothelial cells and neuronal cells. Expression of inducible NOS (iNOS) is induced by inflammatory mediators and is mainly expressed in leucocytes. L-Arginine has shown to scavenge free radicals which are expressed during reperfusion. Its end product NO is an important and potent vasodilatator and prevents aggregation and activation of neutrophils and platelets. Furthermore NO concentrations are reduced during ischemia and production remains low after reperfusion. Therefore increasing NO production by stimulating the L-Arginine-NO pathway may lessen the severity of IR-injury. In experimental studies intravenous L-Arginine substantially reduces ischemia-reperfusion injury in cutaneous and musculocutaneous flaps. The purpose of this translational study was to establish the possible protective effect of L-arginine on microvascular perfusion and clinical outcome in free flap surgery.
Doel van het onderzoek
L-arginine, a precursor of NO, reduces ischemia-reperfusion injury and increases microcirculatory bloodflow. This will lead to a reduction of complications in free flap surgery.
Onderzoeksopzet
1. After flap dissection;
2. ischemia;
3. reperfusion;
4. 1,2,3,4,5 hours after reperfusion;
5. 1 week outpatient clinic;
6. 6 week outpatient clinic.
Onderzoeksproduct en/of interventie
Patients received intravenously one liter of either L-arginine (verum group, 30 g L-arginine-HCl / 1L 0.9% NaCl) or an Alanine (placebo group, 25.2 g Alanine / 1L 0.9% NaCl) during a 24 hour period.
Publiek
R.R.W.J. Hulst, van der
Maastricht 6202 AZ
The Netherlands
+ 31 433875624
rvh@spch.azm.nl
Wetenschappelijk
R.R.W.J. Hulst, van der
Maastricht 6202 AZ
The Netherlands
+ 31 433875624
rvh@spch.azm.nl
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
All patients with free TRAM flap breast reconstruction.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
Previous midline laparotomy.
Opzet
Deelname
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
Register | ID |
---|---|
NTR-new | NL688 |
NTR-old | NTR1626 |
Ander register | : |
ISRCTN | ISRCTN wordt niet meer aangevraagd |
Samenvatting resultaten
2. Booi DI, Debats IB, Boeckx WD, van der Hulst RR. Risk factors and blood flow in the free TRAM flap: Smoking and high flap weight impair the free TRAM flap microcirculation. Ann Plast Surg. 2007 Oct; 59(4):364-71
3. Booi DI, Debats IB, Boeckx WD, van der Hulst RR. Laser Doppler Flowmetry in the free TRAM flap when using zone IV: a clinical study indicating a 48 hour delay in choke vessel opening. JPRAS 2008 March; 61(3):282-8
4. Debats IB, Booi DI, Wehrens KWE, Van den Hogen E, Deutz NE, Bemelmans MHA, van der Hulst RR. Oral arginine supplementation and the effect of skin graft donor sites; a randomized clinical pilot study. Accepted for publication in J Burn Care and Res.
5. Booi DI, Wehrens KWE, Lievaart V, Debats IB, Marcus MAE, van der Hulst RR. Peri-operative fluid overload increases postoperative complications in the free TRAM flap. Submitted for publication.