Proinflammatory Cytokines Gene Expression in Skin Flaps with Arterial and Venous Ischemia in Rats

Zhang, Feng; Hu, Eric C.; Topp, Shelby G.; Lei, Man-Ping; Chen, Weijia; Lineaweaver, William C.

doi:10.1055/s-2006-956238

Cited by 14 publications

(9 citation statements)

References 38 publications

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“…112 Subcutaneous VEGF injection into rat dorsal flaps before elevation significantly decreased expression of TNF-α, a cytokine implicated in tissue injury associated with reperfusion. 118,119 VEGF Gene Therapy VEGF availability to the flap site is poorly sustained due to its short half-life. Gene therapy is an attractive option for potential treatment of nonhealing wounds.…”

Section: Pathway Of Vegf Cascadementioning

confidence: 99%

Effects of Vascular Endothelial Growth Factor on Survival of Surgical Flaps: A Review of Experimental Studies

Fang

Lineaweaver

Chen

et al. 2013

J reconstr Microsurg

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Partial or complete necrosis of skin flaps remains a significant problem in plastic and reconstructive surgery. Growth factors have shown promise in improving flap survival through increased angiogenesis and blood supply to the flap. Vascular endothelial growth factor (VEGF) is the most widely investigated and successful one. But the mechanisms of the effects are still not very clear. In the course of a series of experiments, we indicated that tissue survival of surgical flaps could be improved by both preoperative (sustained phase effect) and intraoperative (acute phase effect) application of VEGF. We reviewed both experimental and clinical investigations on the use of VEGF with surgical flaps to summarize the evidence of both phases of VEGF activity in promotion of flaps survival in detail. With the combinations of acute and sustained phases of effects, VEGF protein and gene, VEGF morphologic actions, and VEGF histochemical modulations suggest a pattern of VEGF activity that can be superimposed on classic descriptive mechanisms of tissue survival of flaps.

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Section: Pathway Of Vegf Cascadementioning

confidence: 99%

Effects of Vascular Endothelial Growth Factor on Survival of Surgical Flaps: A Review of Experimental Studies

Fang

Lineaweaver

Chen

et al. 2013

J reconstr Microsurg

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“…The activation and recruitment of PMNs is modulated by many inflammatory mediators. Recent studies have shown that the cascading overexpression of various inflammatory mediator genes, such as tumor necrosis factor-a, interleukin-1b, 9 intercellular adhesion molecule-1, 10 CD18, [11][12][13] and E/L-selectin, 14 may be the underlying molecular mechanism of PMN activation and recruitment in the early reperfusion period. However, it has become evident that these fundamental biological systems are controlled by many interrelated pathways.…”

Section: Figurementioning

confidence: 99%

“…Much research in flap I/R injury has focused on the signaling processes within the immune system that activate PMN, recruit them from the periphery, cause adherence to the endothelium, and stimulate the ''respiratory burst'' or release of cytodestructive agents. 8 Recent studies showed that up-regulated expression of proinflammatory molecules, such as tumor necrosis factor-a and interleukin-1b, 9 intercellular adhesion molecule-1, 10 CD18, [11][12][13] and E/L-selectin, 14 were responsible for the activation and infiltration of PMNs. However, the exact mechanisms responsible for the up-regulation of those mediators have not yet been well defined.…”

mentioning

confidence: 99%

Protective Effect of a Nuclear Factor-Kappa B Inhibitor on Ischemia-Reperfusion Injury in a Rat Epigastric Flap Model

Yu²,

Li³

2008

J reconstr Microsurg

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We examined whether nuclear factor-kappa B (NF-kappaB) activation was involved in the ischemia-reperfusion (I/R) injury in a rat skin flap model and whether administration of pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, could improve flap viability. Eighty-four Sprague-Dawley rats were divided into control group (n = 28), I/R group (n = 28), and PDTC-treated group (n = 28). An abdominal skin flap (4 x 5 cm) was elevated and subjected to 10 hours of ischemia in both the I/R group and the PDTC-treated group. A bolus of PDTC (300 mg/kg) was infused 5 minutes before reperfusion, followed by a second dose during the first 30 minutes of reperfusion in the PDTC-treated group. Flap tissues were assessed by electrophoretic mobility shift assay at 1, 2, 3, and 6 hours of reperfusion, and myeloperoxidase activity and neutrophil infiltration were assessed at 12 hours of reperfusion. The viability of flaps was assessed 7 days postoperatively. NF-kappaB was activated after reperfusion in the I/R group and displayed peak activity at 1 and 3 hours of reperfusion. In the PDTC-treated group, NF-kappaB activity was significantly reduced at 1, 2, and 6 hours of reperfusion. Myeloperoxidase activity was significantly decreased, and little neutrophil infiltration could be observed. In the PDTC-treated group, the survival of flaps was 86.88 +/- 13.63%, which was significantly greater than the I/R group, in which only 19.20 +/- 7.52% of the flap survived. NF-kappaB is activated during reperfusion in a rat skin flap I/R model. Administration of PDTC can significantly improve flap survival by regulating the early activation of NF-kappaB and suppressing neutrophil infiltration within the flap.

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“…Only a limited number of studies have compared transcriptional changes in arterial ischemia and venous congestion. Zhang et al used a skin flap model and found that tumor necrosis factor (TNF-alpha) was significantly up-regulated in arterial ischemia, whereas monocyte chemoattractant protein-1 (MCP-1) was associated with venous congestion [40]. Mithani et al used a rat flap model to identify genes related to flap failure, but only studied venous congestion [41].…”

Section: Introductionmentioning

confidence: 99%

Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

et al. 2013

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The field of reconstructive microsurgery is experiencing tremendous growth, as evidenced by recent advances in face and hand transplantation, lower limb salvage after trauma, and breast reconstruction. Common to all of these procedures is the creation of a nutrient vascular supply by microsurgical anastomosis between a single artery and vein. Complications related to occluded arterial inflow and obstructed venous outflow are not uncommon, and can result in irreversible tissue injury, necrosis, and flap loss. At times, these complications are challenging to clinically determine. Since early intervention with return to the operating room to re-establish arterial inflow or venous outflow is key to flap salvage, the accurate diagnosis of early stage complications is essential. To date, there are no biochemical markers or serum assays that can predict these complications. In this study, we utilized a rat model of flap ischemia in order to identify the transcriptional signatures of venous congestion and arterial ischemia. We found that the critical ischemia time for the superficial inferior epigastric fasciocutaneus flap was four hours and therefore performed detailed analyses at this time point. Histolgical analysis confirmed significant differences between arterial and venous ischemia. The transcriptome of ischemic, congested, and control flap tissues was deciphered by performing Affymetrix microarray analysis and verified by qRT-PCR. Principal component analysis revealed that arterial ischemia and venous congestion were characterized by distinct transcriptomes. Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold differentially expressed genes, respectively. qRT-PCR was used to identify five candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for flap failure in both arterial ischemia and venous congestion. Our data suggests that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow clinicians to both diagnose and successfully treat microvascular complications before irreversible tissue damage and flap loss occurs.

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Proinflammatory Cytokines Gene Expression in Skin Flaps with Arterial and Venous Ischemia in Rats

Cited by 14 publications

References 38 publications

Effects of Vascular Endothelial Growth Factor on Survival of Surgical Flaps: A Review of Experimental Studies

Effects of Vascular Endothelial Growth Factor on Survival of Surgical Flaps: A Review of Experimental Studies

Protective Effect of a Nuclear Factor-Kappa B Inhibitor on Ischemia-Reperfusion Injury in a Rat Epigastric Flap Model

Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

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