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Use Of Near-infrared Fluorescence Imaging To Assess Impact Of CiNPT On Lymphatic Activity
Marisa Schmidt, B.S.1, Eva Sevick, Ph.D.2, John Rasmussen, Ph.D.2, Ronald Silverman, M.D.3, Kris Kieswetter, Ph.D.1.
1Kinetic Concepts Inc, San Antonio, TX, USA, 2Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA, 3Kinetic Concepts Inc., San Antonio, TX, USA.

PURPOSE: 
Studies (Cheong, et al. 2013; Hamed, et al. 2008; Stannard, et al. 2006) have demonstrated that the use of closed incisional negative pressure therapy (ciNPT) decreases rates of surgical site complications such as hematoma/seroma, lymphocele, and post-surgical edema. It has been shown in animals (Kilpadi, et al. 2011) that ciNPT results in increased drainage to lymph nodes, but the mechanism of action has not been directly evaluated. It is hypothesized that one of the mechanisms of action of ciNPT is the mechanical stimulation of lymphatic pumping or contractile activity of regional lymphatic vessels. 
METHODS: 
In this work a near-infrared fluorescence lymphatic imaging system (Sharma, et al. 2007) is utilized in a surgical incision swine model using undermining and impaired perfusion (Ashitate, et al. 2018) to longitudinally quantify lymphatic activity (contractile events/minute) in caudal-draining lymph vessels running through incisional sites treated with ciNPT* or untreated controls. A model of surgical edema was created by making semi-circumferential incisions with undermining to transect lymphatic vessels on a pair of contralateral teats. Lymphatic pumping assessments of ciNPT were performed on anesthetized swine prior to and at 2, 50, 146, and 218 hours after surgery using 100 uL of 0.25 mg/mL indocyanine green injected cranial to the surgical sites. Comparisons were made against contralateral, untreated surgical sites covered with a polyurethane film. 
RESULTS: 
Using fluorescence NIR, the effects of surgical edema caused by lymphatic vessel transection was visualized directly. Edema was evidenced by an immediate decrease in lymphatic pumping and subsequent pooling in undermined areas. Quantitative methods for measuring propulsion events showed an increase in lymphatic activity using ciNPT as compared to untreated controls. Lymphatic pumping was restored faster to baseline values in ciNPT-treated sites when compared contralateral, non-treated sites. 
CONCLUSIONS: 
This model was able to successfully demonstrate decreased lymphatic pumping rates immediately after surgery with an improved recovery of lymphatic pumping over time using ciNPT compared to contralateral, untreated controls. 
1 Cheong YK, Jun H, Cho YP, et al. Negative pressure wound therapy for inguinal lymphatic complications in critically ill patients. J Korean Surg Soc. 2013;85(3):134–138.
2 Hamed O, Muck PE, Smith JM, et al. Use of vacuum-assisted closure (VAC) therapy in treating lymphatic complications after vascular procedures: new approach for lymphoceles. J Vasc Surg. 2008 Dec;48(6):1520-3, 1523.e1-4.
3 Stannard J, Robinson J, Anderson E, et al. Negative pressure wound therapy to treat hematomas and surgical incisions following high-energy trauma. J Trauma. 2006. 60(6):1301-1306.
4 Kilpadi D, Cunningham M. Evaluation of closed incision management with negative pressure wound therapy (CIM): hematoma/seroma and involvement of the lymphatic system. Wound Repair Regen 2011;19:588-96.
5 Sharma R, Wang W, Rasmussen J, et al. Quantitative imaging of lymph function. Am J Physiol Heart Circ Physiol 2007. 292: H3109–H3118.
6 Ashitate Y, Lee BT, Ngo LH, et al. Quantitative Assessment of Nipple Perfusion with Near-Infrared Fluorescence Imaging. Ann Plast Surg. 2013 Feb; 70(2): 149–153.
* PREVENA™ PEEL & PLACE™ System Kit – 13cm, Kinetic Concepts Inc., San Antonio, Texas


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