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Modification of a rodent hindlimb model of secondary lymphedema: surgical radicality versus radiotherapeutic ablation.

ABSTRACT: Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of superficial and deep lymphatic vessels, surgery alone was not enough to sustain increased hindlimb volume. Radiotherapy was necessary to prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The applicability of this model for studies of therapeutic lymphangiogenesis was subsequently tested by injecting muscle-derived stem cells previously cocultured with the supernatant of human lymphatic endothelial cells in vitro. There was a tendency for increased lymphatic flow which significantly increased lymphatic vessel formation after cell injection, but attenuation of hindlimb volume was not observed. These results suggest that further refinement of the rodent hindlimb model is needed by titration of adequate radiation dosage, while stem cell lymphangiogenesis seems to be a promising approach.

SUBMITTER: Park HS

PROVIDER: S-EPMC3856125 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Modification of a rodent hindlimb model of secondary lymphedema: surgical radicality versus radiotherapeutic ablation.

Park Hyung Sub HS Jung In Mok IM Choi Geum Hee GH Hahn Soli S Yoo Young Sun YS Lee Taeseung T

BioMed research international 20131114

Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of ...[more]

PMID: 24350251

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Project description:BACKGROUND:Pulsed field ablation (PFA) can be myocardium selective, potentially sparing the esophagus during left atrial ablation. In an in vivo porcine esophageal injury model, we compared the effects of newer biphasic PFA with radiofrequency ablation (RFA). METHODS:In 10 animals, under general anesthesia, the lower esophagus was deflected toward the inferior vena cava using an esophageal deviation balloon, and ablation was performed from within the inferior vena cava at areas of esophageal contact. Four discrete esophageal sites were targeted in each animal: 6 animals received 8 PFA applications/site (2 kV, multispline catheter), and 4 animals received 6 clusters of irrigated RFA applications (30 W×30 seconds, 3.5 mm catheter). All animals were survived to 25 days, sacrificed, and the esophagus submitted for pathological examination, including 10 discrete histological sections/esophagus. RESULTS:The animals weight increased by 13.7±6.2% and 6.8±6.3% (P=0.343) in the PFA and RFA cohorts, respectively. No PFA animals (0 of 6, 0%) developed abnormal in-life observations, but 1 of 4 RFA animals (25%) developed fever and dyspnea. On necropsy, no PFA animals (0 of 6, 0%) demonstrated esophageal lesions. In contrast, esophageal injury occurred in all RFA animals (4 of 4, 100%; P=0.005): a mean of 1.5 mucosal lesions/animal (length, -21.8±8.9 mm; width, -4.9±1.4 mm) were observed, including one esophago-pulmonary fistula and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by acute and chronic inflammation and fibrosis. The necrotic RFA lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of periesophageal nerves. Abscess formation and full-thickness esophageal wall disruptions were seen in areas of perforation/fistula. CONCLUSIONS:In this novel porcine model of esophageal injury, biphasic PFA induced no chronic histopathologic esophageal changes, while RFA demonstrated a spectrum of esophageal lesions including fistula and deep esophageal ulcers and abscesses.

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Modification of a rodent hindlimb model of secondary lymphedema: surgical radicality versus radiotherapeutic ablation.

Publications

Modification of a rodent hindlimb model of secondary lymphedema: surgical radicality versus radiotherapeutic ablation.

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