ABSTRACT
BACKGROUND: Cold ischemia-reperfusion injury is unavoidable during organ transplantation, and prolonged preservation is associated with poorer function recovery. Cardiotrophin-1 (CT-1) is an IL-6 family cytokine with cytoprotective properties. This preclinical study in rats tested whether CT-1 mitigates cold renal ischemia-reperfusion injury in the context of the transplantation of long-time preserved kidneys. METHODS: Kidneys were flushed with cold (4°C) University of Wisconsin solution containing 0.2 µg/mL CT-1 and stored for several periods of time at 4°C in the same solution. In a second approach, kidneys were first cold-preserved for 6 hours and then were perfused with University of Wisconsin solution containing CT-1 (0, 16, 32, or 64 µg/mL) and further cold-preserved. Organ damage markers were measured in the kidneys at the end of the storage period. For renal transplantation, recipient consanguineous Fischer rats underwent bilateral nephrectomy and received a previously cold-preserved (24 hours) kidney as described above. Survival and creatinine clearance were monitored over 30 days. RESULTS: Cardiotrophin-1 in perfusion and preservation fluids reduced oxidative stress markers (superoxide anion and inducible nitric oxide synthase), inflammation markers (NF-κB and tumor necrosis factor-α), and vascular damage (vascular cell adhesion molecule-1) and activated leukemia inhibitory factor receptor and STAT-3 survival signaling. Transplantation of kidneys cold-preserved with CT-1 increased rat survival and renal function (ie, lower plasma creatinine and higher creatinine clearance) and improved kidney damage markers after transplantation (ie, lower superoxide anion, tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 and higher NF-κB). CONCLUSIONS: Cardiotrophin-1 represents a novel therapeutic strategy to reduce ischemia-reperfusion and cold preservation injury to rescue suboptimal kidneys and, consequently, to improve the clinical outcomes of renal transplantation.
Subject(s)
Cytokines/therapeutic use , Kidney Transplantation/adverse effects , Organ Preservation/methods , Reperfusion Injury/prevention & control , Tissue and Organ Harvesting/methods , Adenosine/chemistry , Allografts/blood supply , Allografts/drug effects , Allopurinol/chemistry , Animals , Cold Ischemia/adverse effects , Cytokines/pharmacology , Disease Models, Animal , Glutathione/chemistry , Graft Survival/drug effects , Humans , Insulin/chemistry , Kidney/blood supply , Kidney/drug effects , Kidney Function Tests , Kidney Transplantation/methods , Male , Nephrectomy , Organ Preservation Solutions/chemistry , Perfusion/methods , Raffinose/chemistry , Rats , Rats, Inbred F344 , Reperfusion Injury/etiology , Tissue and Organ Harvesting/adverse effectsABSTRACT
The gracilis muscle has been used extensively in reconstructive surgery, based on the proximal dominant pedicle. In the literature, little attention has been paid to the secondary distal pedicles. The distribution of the secondary pedicles of the gracilis muscle was investigated in 20 cadaver thighs. The mean number of secondary pedicles was 2.2 (range, two to three). When two pedicles were present-the most common situation-they were located at a mean distance of 12.4 and 17.5 cm from the knee joint line. The most proximal secondary pedicle was injected with barium sulfate in five specimens, and constant and abundant connections with the main pedicle were noted. A series of seven clinical cases of segmental gracilis free muscle flaps based on a secondary pedicle is reported. The flaps were successfully transferred to reconstruct traumatic defects of limited size, with one case of partial necrosis caused by a technical error. The morbidity of this flap is minimal, the scar is well hidden, the muscle need not be sacrificed, elevation is fast and straightforward under tourniquet control, and the pedicle is sizable. This flap should be considered a viable option when a small, straightforward free flap is needed.
