J Thorac Cardiovasc Surg 1998;116:397-401
© 1998 Mosby, Inc.
Cardiothoracic Transplantation |
Tracheal transplantation for carinal reconstruction in dogs
Katsunobu Kawahara, MD,
Kouji Inutsuka, MD,
Masafumi Hiratsuka, MD,
Satoshi Makihata, MD,
Kann Okabayashi, MD,
Takeshi Shiraishi, MD,
Takayuki Shirakusa, MD
From the Second Department of Surgery, Fukuoka University School ofMedicine, Fukuoka, Japan.
Received for publication Jan. 19, 1998; revisions requested March 25,1998; revisions received April 20, 1998; accepted for publication April 21,1998.
Address for reprints: Katsunobu Kawahara, MD, Second Department ofSurgery, Fukuoka University School of Medicine, Jyohnannku Nanakuma 7-45-1,814-01, Fukuoka, Japan.
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Abstract
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Background: Experimental carinalallotransplantation has been performed with tracheocarinal Y-shaped allograftsin dogs. In this study we tried canine carinal reconstruction with cylindricalallografts.
Material and methods: Carinal reconstruction wasperformed with allotransplantation of cylindrical trachea in dogs, and grafthealing was evaluated by bronchoscopic observation, mucosal blood flowmeasurement, and histologic examination. A section of the recipient carinacontaining five tracheal rings and two main stem bronchi was removed, and adonor trachea seven rings long was inserted between the recipient trachea andthe left main stem bronchus; then side-to-end anastomosis was performed betweenthe graft midportion and recipient right main stem bronchus (new carina). Thegrafts were wrapped with pedicled omentum. Fresh grafts were transplanted intoone group of dogs (n = 8 ), and graftscryopreserved for 1 week were transplanted into another group (n = 7).
Results:No anastomotic leakage occurred in any dog. Excellent healing of grafts andgraft anastomoses was observed by fiberoptic bronchoscopy in six dogs (75%)in the fresh graft group and in four dogs (57%) in the cryopreservedgraft group. The mucosal blood flow in the new carina decreased remarkably and,although it recovered, mucosal blood flow remained under the preoperative levelon day 28 after the operation.
Conclusion:Cylindrical tracheal allotransplantation is useful for carinal reconstruction,and the method of side-to-end anastomosis between the donor trachea andrecipient bronchus is a feasible and accessible procedure in dogs. (J ThoracCardiovasc Surg 1998;116:397-401)
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Introduction
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Previously we
1,2 documented sufficient viability andgood healing in canine immediate tracheocarinal autotransplantation andallotransplantation. In our previous experiments, canine cryopreservedtracheocarinal allografts healed well in 70% of experimental dogs, andrevascularization of grafts derived from the omentum occurred on day 5. 2 The tracheal membrane blood flow waslower at the midportion of the graft than at the proximal or distal anastomoses,but it had recovered to normal level 4 weeks after the operation. 2
In this present study we tried carinal reconstruction withallotransplantation of fresh and cryopreserved cylindrical trachea in dogs; theprocedure involved inserting a cylindrical graft between the recipient tracheaand left main stem bronchus and performing side-to-end anastomosis between thegraft midportion and the recipient right main stem bronchus. We evaluated thehealing of anastomoses at the midportion of the grafts where mucosal blood flowwas lower than it was in the proximal or distal ends.
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Materials and methods
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Adult mongrel dogs were used as both donors and recipients. All dogs weremaintained according to the National Society at Medical Research Principles ofLaboratory Animal Care. This study was approved by our institutional animal careand review committee.
Donor dogs
Adult mongrel dogs weighing from 10 to 17 kg were anesthetized andintubated. A right thoracotomy was performed, and the trachea and the carinawere isolated. A seven-ring length of mediastinal trachea was harvested.
Cryopreservation
The tracheas were put in sterilized bottles and stored in a freezer at–80° C for 1 to 2 weeks. Before transplantation they were rewarmed at35° C for 15 minutes.
Recipient dogs
Recipient dogs of the same weight as the donor dogs were put in a leftdecubitus position. An upper median laparotomy was performed, and a pedicledomental flap was made and pulled into the right pleural cavity through thediaphragm. Then a right thoracotomy was performed. The azygos vein wastransected, and the trachea and carina were isolated. The right main bronchustwo rings distal to the carina was transected and intubated through the pleuralcavity. Subsequently, the right lung was ventilated, and five rings of thetrachea and two rings of the left main bronchus were transected; then thetrachea and carina were removed en bloc.
The dogs were classified into two groups. In group 1 (n = 8), initially a cylindrical graft of a donortrachea without cryopreservation was inserted between the recipient trachea andthe left main stem bronchus. Subsequently, an orotracheal tube was inserted intothe left main bronchus, and the left lung was ventilated. An oval window wasopened at the cartilaginous wall in the midportion of the graft, and the rightmain bronchus was anastomosed to the window (Fig. 1). After the anastomosis was completed, thegraft was wrapped with the pedicled omentum through the diaphragmatic route. Ingroup 2 (n = 7), a cylindrical graftcryopreserved for 1 week was inserted by means of the same procedure describedfor the group 1 dogs.
Recipient dogs were given antibiotics for 1 week after the operation.Immunosuppressive therapy with administration of FK506, 1.0 mg/kg, was performedfor 4 weeks after the operation and then discontinued.
Bronchoscopic examinations were performed and mucosal blood flows of thegrafts at the anastomoses of the proximal site, distal site, and midportion weremeasured by the hydrogen gas clearance technique 3 after the operation. The anastomotichealing of grafts was examined weekly.
When the recipient dogs were killed, the grafts were removed and examinedhistologically with hematoxylin and eosin staining. The anastomotic healing ofthe graft midportion was histologically evaluated by the wound healing scoresystem of Nakanishi and associates. 4
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Results
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Within 15 days after the operation, one dog in group 1 and two dogs ingroup 2 died as a result of the FK506 administration. Two dogs in group 1 andone dog in group 2 died of pneumonia or respiratory failure with airway stenosisresulting from graft failure. In group 1, three dogs survived for 46 to 74 days,and two dogs are alive 286 and 686 days after the operation (Table I). Survival in group 1 was five of eight dogs (62%),with 70% confidence limits from 38% to 83%. In group 2, twodogs survived for 34 and 56 days after the operation, and two dogs were alivefor 313 and 553 days after the operation (Table I). Survival in group 2 was fourof seven dogs (57%), with 70% confidence limits from 32% to82%.
No anastomotic leakage occurred in any dog. Excellent healing of graftand graft anastomoses was observed by fiberoptic bronchoscopy in six of eightdogs (75%) in group 1, with 70% confidence limits from 50%to 90%, and in four of seven dogs (57%) in group 2, with 70%confidence limits from 32% to 80% (Figs. 2 and 3).
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Fig. 2. Macroscopic photographof the graft on postoperative day 40. The omentum with which the graft had beenwrapped was removed.
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Fig. 3.Bronchofiberscopic findings of the anastomoses inthe graft: Proximal anastomosis (A), new carina(B), and distal anastomosis (C) are shown.
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The histologic healing score of the dogs, except living dogs, was 6, 6,and 7 in group 1 and 5 and 9 in group 2 (Table I). Microscopic findings areshown in Fig. 4. Epithelialization of the anastomosis wasaccomplished within approximately 3 weeks of transplantation in all groups. Thehealing score in the dogs with graft failure was 15 and 16 in group 1 and 12,15, and 16 in group 2.
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Fig. 4. Microscopic photographof the anastomosis at the new carina. Mononuclear cell infiltration and agranulation tissue-like reaction with fibrosis are absent. Normal mucociliaryepithelium covers the graft, and no damage to the tracheal glands or cartilageis observed.
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Histologically, cartilaginous degeneration and necrosis of the graftswere observed in the dogs that died of graft failure. The mononuclear cellinfiltration was limited.
The mucosal blood flow at the graft anastomoses decreased from day 3 today 7 after the operation, and then it recovered to preoperative levels afterday 28 in both the groups. The mucosal blood flow of the grafts at theanastomosis between the graft and the right main stem bronchus (new carina)decreased remarkably after transplantation and then increased gradually, but itremained under the preoperative level on day 28.
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Discussion
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In this study, we demonstrated that a cylindrical allograft of thetrachea was useful for carinal reconstruction involving allotransplantation ofthe canine trachea. Although mucosal blood flow in the midportion of acylindrical graft was lower than that in the proximal or distal site of thegraft, a side-to-end anastomosis between the midportion of the allograft and therecipient bronchus was feasible, and graft healing was excellent. We estimatedthe dehiscence in the side-to-end anastomosis of the graft and recipientbronchus because, in our previous study, the tracheal mucosal blood flow waslower at the midportion of the grafts than that at the proximal or distalanastomotic site of the grafts; however, dehiscence did not occur in thiscurrent study. Yokomise and colleagues 5reported that neovascularization of a 10 cm long graft was promoted by omentuminsertion at the midportion of the graft. Kitada 6 reported that a circular incision inthe long graft further enhanced the blood supply to the midportion of the graft.In our study, although the omentum was not inserted, revascularizationoriginating from the omentum could be accomplished rapidly at the side-to-endanastomosis at the midportion of the graft (new carina); therefore, anastomoticdehiscence did not occur. It normally takes 2 to 3 weeks after lungtransplantation for bronchial circulation to be restored by means of vasculargrowth across the healing bronchial anastomosis. Collateral circulation betweenomental vessels and bronchial vessels distal to the bronchial anastomosis hadbeen accomplished by 4 days after the operation. 7 Nakanishi, Shirakusa, and Takachi 8 reported that omentopexy is aneffective method to facilitate neovascularization in tracheal allografts.Therefore, to restore tracheal circulation and protect the anastomosis, weinstituted the procedure of wrapping a pedicle of omentum around the trachealanastomosis after its completion. Blood flow of the omentum and vascularizationof the tracheal adventitia are very important factors for success of trachealallotransplantation. The omentum should not be twisted or stretched when it isbrought into the chest and wrapped around the graft. Furthermore, connectivetissues surrounding the trachea should not be dissected when the grafts areharvested.
Cylindrical grafts are convenient because they can be used for anyreconstruction of the central airway. A Y-shaped graft can be used only forcarinal reconstruction. Furthermore, more than two cylindrical allografts can beharvested from one donor, but only one Y-shaped allograft can be harvested fromone donor.
In canine tracheal allotransplantation, grafts resisted rejection andimmunosuppression when only a short course of mizoribine was administered aftertransplantation, allowing the possibility of long-term viability. 9 Yokomise and colleagues 10 reported thatimmunosuppressant-free canine tracheal allotransplantation was consistentlypossible after long-term cryopreservation of a graft in a preservative solutioncontaining trehalose. In our study, an immunosuppressant was administered for 4weeks after the operation and then discontinued. After discontinuation ofimmunosuppressant, graft failure was not observed in either dogs with freshgrafts or those with grafts cryopreserved for 1 week.
We conclude that allotransplantation of a cylindrical trachea is usefulfor carinal reconstruction and that the side-to-end anastomosis between donortrachea and recipient bronchus is a feasible and reliable procedure in dogs.
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Footnotes
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12/1/91178
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References
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Takachi T, Shirakusa T, Shiraishi T,Okabayashi K, Inutsuka K, Kawahara K, et al. Experimental carinalautotransplantation and allotransplantation. J Thorac Cardiovasc Surg 1995;110:762-7.[Abstract/Free Full Text]
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Aukland K, Bower BF, Berliner RW. Measurementof local blood flow with hydrogen gas. Circ Res 1964;14:164-87.[Abstract/Free Full Text]
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Nakanishi R, Shirakusa T, Hanagiri T. Earlyhistopathologic features of tracheal allotransplant rejection: a study innonimmunosuppressed dogs. Transplant Proc 1994;26:3715-8.[Medline]
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Yokomise H, Inui K, Wada H, Ueda M, Hitomi S,Ito H. Split transplantation of the trachea: a new operative procedure forextended tracheal resection. J Thorac Cardiovasc Surg 1996;112:314-8.[Abstract/Free Full Text]
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Kitada M. Study of revascularization oftracheal graft in a canine autotransplantation model—a novel technique topromote blood supply to a long graft. Nippon Kyoubu Geka Gakkai Zasshi 1996;44:2011-8.
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Nakanishi R, Shirakusa T, Takachi T.Omentopexy for tracheal autografts. Ann Thorac Surg 1994;57:841-5.[Abstract]
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Nakanishi R, Yasumoto K, Shirakusa T.Short-course immunosuppression after tracheal allotransplantation in dogs. J Thorac Cardiovasc Surg 1995;109:910-17.[Abstract]
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Yokomise H, Inui K, Wada H, Ueda M, Hitomi S.Long-term cryopreservation can prevent rejection of canine tracheal allograftswith preservation of graft viability. J Thorac Cardiovasc Surg 1996;111:930-4.[Abstract/Free Full Text]
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Abstract
Introduction
