Heterotopic cardiac xenotransplantation in rodents: Report of a refined technique in a hamster‐to‐rat model

Dedja, Arben; Dall’Olmo, Luigi; Cadrobbi, R.; Baldan, N; Fante, F; Calabrese, Fiorella; Rigotti, Paolo; Ferraresso, Mariano; Delrivière, Luc; Ancona, Ermanno

doi:10.1002/micr.20101

Cited by 13 publications

(14 citation statements)

References 24 publications

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“…At T = 30 weeks post-surgery, WLE showed that 10/46 rats had normal mucosa, or little and rare mucosal erosions (mild esophagitis); 28/46 rats had endoscopic appearance of BE with or without severe ulcerations but without visible lesions suggestive of cancer, and 8/46 had endoscopic appearance of BE and visible lesions suggestive of cancer. As already described, 36 none of the 46 rats displayed salmon-colored mucosa characteristic of intestinal metaplasia, as found in human esophagus. Endoscopic examination of the eight long-term surviving control rats did not reveal any abnormal findings (Fig.…”

Section: Wle Findingssupporting

confidence: 52%

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In vivomolecular imaging of HER2 expression in a rat model of Barrett's esophagus adenocarcinoma

et al. 2014

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Human epidermal growth factor receptor 2 (HER2) is involved in the malignant progression of several human cancers, including esophageal adenocarcinoma (EAC). The purpose of this study was to evaluate HER2 overexpression and to explore the feasibility of confocal laser endomicroscopy for in vivo molecular imaging of HER2 status in an animal model of Barrett's-related EAC. Rats underwent esophagojejunostomy with gastric preservation. At 30 weeks post-surgery, the esophagus of 46 rats was studied; endoscopic and histological findings were correlated with HER2 immunofluorescence on excised biopsies and gross specimens. At this age, 23/46 rats developed Barrett's esophagus (BE), and 6/46 had cancer (four EAC and two squamous cell carcinomas). A significant overexpression of HER2 was observed in esophageal adenocarcinoma compared with normal squamous esophagus (9.4-fold) and BE (6.0-fold). AKT and its phosphorylated form were also overexpressed in cancer areas. Molecular imaging was performed at 80 weeks post-surgery in four rats after tail injection of fluorescent-labeled anti-HER2 antibody. At this age, 3/4 rats developed advance adenocarcinoma and showed in vivo overexpression of HER2 by molecular confocal laser endomicroscopy with heterogeneous distribution within cancer; no HER2 signal was observed in normal or Barrett's tissues. Therefore, HER2 overexpression is a typical feature of the surgical induced model of EAC that can be easily quantified in vivo using an innovative mini-invasive approach including confocal endomicroscopy; this approach may avoid limits of histological evaluation of HER2 status on 'blinded' biopsies.

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Section: Wle Findingssupporting

confidence: 52%

“…The operation was performed according to the microsurgical procedure previously described. [31][32][33][34][35][36] None of the drugs used are known to be carcinogens.…”

Section: Surgical Proceduresmentioning

confidence: 99%

In vivomolecular imaging of HER2 expression in a rat model of Barrett's esophagus adenocarcinoma

et al. 2014

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“…This model was even used for xenotransplantation experiments. 10,11 Because of the high rate of postoperative loss of grafts and animals, modifications of the Ono and Lindsey method were proposed, including vascular graft, 8 removal of the left kidney, 9 or volume-loaded heart transplantation. 12 These modifications could not satisfactorily improve the results and therefore many microsurgeons continue to use the Ono and Lindsey method.…”

Section: Resultsmentioning

confidence: 99%

“…6,10 It is known that the success of intervention correlates with operation time. [13][14][15][16][17] It was shown repeatedly that long ischemia and long operation times are associated with low graft survival rates, 10,11 and conversely, that short ischemia and operation times are associated with better graft and recipient survival. 7,8 By using a Cooley ATRAU-MATA-vascular clamp, we omitted the ligation of branches, thus decreasing the trauma, the incidence of thrombosis, and together with the modified venotomy we considerably reduced the operation time.…”

Section: Resultsmentioning

confidence: 99%

A simplified technique for heart transplantation in rats: Abdominal vessel branch-sparing and modified venotomy

2006

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Heterotopic heart transplantation in rats has been a widely used model in immunology since Ono and Lindsey published their technique. However, variable graft survival rates were reported by different authors with this method. With the development of microsurgery and new instruments, amendment of this technique became possible. The authors described an improved Ono-Lindsey method, based on branch-sparing and venotomy modifications, leading to a significantly shortened ischemia (25 min) and operation time (40 min), minimal postoperative complications, and considerably improved graft survival.

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With great interest we read the article by Dedja et al, reporting a refined technique for hamster-to-rat heterotopic cardiac xenotransplantation. 1 The article provides novel insights in the distinct technique implemented at the authors' institution and describes methodological improvements, adaptions, and further changes of the suture technique for heterotopic heart transplantation in rodents, initially described by Abbott et al and Ono and Lindsay. 2,3 Further, Dedja et al refined earlier instructions for this experimental model to perform heterotopic cardiac xenotransplantation in the hamster-to-rat combination.

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mentioning

confidence: 99%

Heterotopic cardiac xenotransplantation in rodents: Report of a refined technique in a hamster-to-rat model

Schramm¹,

Schäfers²,

Hamacher³

et al. 2006

Microsurgery

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With great interest we read the article by Dedja et al.,reporting a refined technique for hamster-to-rat heterotopic cardiac xenotransplantation. 1 The article provides novel insights in the distinct technique implemented at the authors' institution and describes methodological improvements, adaptions, and further changes of the suture technique for heterotopic heart transplantation in rodents, initially described by Abbott et al. and Ono and Lindsay. 2,3 Further, Dedja et al. refined earlier instructions for this experimental model to perform heterotopic cardiac xenotransplantation in the hamster-to-rat combination. [1][2][3] We feel that particularly, the step-by-step instructions on both the microsurgical procedures and the anesthetic interventions are thoroughly described, which allows for an easy adoption of this experimental model by the reader.In view of using this model for the study of specific immunological processes in xenograft rejection, however, the technique described bears the major drawback in that the procedure is associated with an enhancement of nonspecific ischemia/reperfusion injury, which may markedly interfere with immunological analyses of xenograft rejection. We therefore would like to suggest additional refinements in order to alleviate the assessment of the purely adaptive immune responses during experimental cardiac xenograft rejection. It should be favored to reduce functional graft impairment due to innate immunity and nonspecific ischemia/reperfusion (I/R) injury.Dedja et al. describe in detail the harvest of the hamster donor organ.1 This includes heparinization via the abdominal inferior vena cava (IVC), subsequent thoracotomy, isolation and transection of both the proximal aorta and pulmonary trunk, organ preservation by manual retrograde injection of ice-cold Celsior 1 solution (Imtix, Sangstat Italia, Milan, Italy) into the proximal aorta, mass ligature of the residual pericardial structures as well as minor back table preparation of the graft. We support this straight forward harvesting protocol, particularly the use of a mass ligature for combined transection of all residual pericardial tissues. This procedure, which was first described by Heron, indeed helps to drastically reduce the time of harvest and thus the graft's total ischemia time.4 Nonetheless, Dedja et al. use retrograde manual injection of the preservation solution via the ascending aorta at 10 ml/min or more slowly for the preservation of the graft subsequent to the thoracotomy as well as the isolation and transection of the great thoracic vessels. By this, the graft has to be considered to be exposed to a certain period of warm ischemia, which ideally should be omitted. We favor to cannulate the intraabdominal aorta and to begin the cold perfusion of the graft by standardized continuous infusion of preservation solution at a stable pressure of 100 cm H 2 O already before thoracotomy. This also guarantees that the donor blood is flushed out of the coronary system to minimize the risk of coronary microthrombosi...

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Heterotopic cardiac xenotransplantation in rodents: Report of a refined technique in a hamster‐to‐rat model

Cited by 13 publications

References 24 publications

In vivomolecular imaging of HER2 expression in a rat model of Barrett's esophagus adenocarcinoma

In vivomolecular imaging of HER2 expression in a rat model of Barrett's esophagus adenocarcinoma

A simplified technique for heart transplantation in rats: Abdominal vessel branch-sparing and modified venotomy

Heterotopic cardiac xenotransplantation in rodents: Report of a refined technique in a hamster-to-rat model

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