Successful revascularization of totally ischemic bronchial autografts with omental pedicle flaps in dogs

J THORAC CARDIOVASC SURG 84:204-210, 1982

Successful revascularization of totally ischemic bronchial autografts with omental pedicle flaps in dogs In 10 dogs, the left lung was removed and a closed stump of bronchus, comprising the distal main and lobar bronchi, was reanastomosed to the main bronchus. This totally ischemic cul-de-sac of bronchus was wrapped by an omental flap in five of the 10 dogs. All dogs without an omental wrap died of graft necrosis within 5 days. Injection studies into the bronchial arteries failed to demonstrate any revascularization of the bronchial grafts. In contrast, those dogs with omental wraps, when put to death at 23 days, displayed healthy viable bronchial grafts with full revascularization from the omental vessels. In another three dogs the revascularization via the omentum was demonstrated as early as 4 days and well established at 8 days. The ability of the omentum to rapidly revascularize the bronchus may be of value in potentially ischemic bronchial anastomoses such as in lung transplantation.

E. Morgan, M.D., Ch.B.,* O. Lima, M.D., Ph.D., M. Goldberg, M.D., A. Ferdman, M.D., S. K. Luk, M.D., and J. D. Cooper, M.D., Toronto, Ontario, Canada

Impaired bronchial healing following lung transplantation remains a major problem. I, 2 As with any major organ transplant, the healing process may be adversely affected by rejection, infection, drug therapy, and the general debility of the patient. In lung transplantation an additional problem is ischemia of the donor bronchus, which has been completely separated from its systemic blood supply and is dependent on communications with the pulmonary circulation.P: 4 The period of ischemia will persist until adequate revascularization from the recipient bronchial circulation is established, a process which may take 12 to 15 days.": 6 Recently we 7 reported the successful revascularization of the donor bronchus at 4 days using an omental pedicle wrap around the broncial anastomosis in a

canine left lung reimplantation. Encouraged by this result, we decided to test the efficacy of the omental pedicle flap in revascularizing a totally ischemic bronchial autograft model in dogs. Methods

Address for reprints: Joel D. Cooper, M.D., 10-226 Eaton Building, Toronto General Hospital, 200 Elizabeth St., Toronto, Ontario, Canada M5G 1L7. *Present address: Department of Thoracic Surgery, City Hospital, Nottingham, England. Ethicon UK and Wellcome UK Travel Scholarship.

Ten mongrel dogs weighing 18 to 27 kg were randomly allocated into two groups: The five dogs in Group A received bronchial autografts and the other five dogs, in Group B, received bronchial autografts with an omental pedicle flap. Three additional dogs, composing Group C, underwent left bronchial autograft with omental pedicle wrap and were put to death at 4, 5, and 8 days in order to assess the time course of bronchial revascularization via the omental vessels. Following premedication with intramuscular droperidol and fentanyl citrate (lnnovar- Vet), 1 mIl 10 kg, general anesthesia was induced with intravenous thiopentone and maintained with a fluothane/oxygen mixture via an endotracheal tube. Atropine, 0.05 mg/ kg, and cefazolin (Ancef ), I gm, were administered intravenously at the time of induction. No further antibiotics were given. Bronchial autograft-operative technique. Through an incision in the left sixth intercostal space, the left pulmonary artery and veins were ligated and divided. The lung parenchyma was dissected off the bronchial

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0022-5223/82/080204+07$00.70/0 © 1982 The C. V. Mosby Co.

From the Division of Thoracic Surgery, University of Toronto, Toronto, Ontario, Canada. Supported in part by a grant from the Medical Research Council of Canada (MA 6909). Received for publication Oct. 9, 1981. Accepted for publication Dec. 2, 1981.

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Table I Dog No.

2 3 4

5

6 7

8 9 10

20 5

> Survival and cause of death Group A -no omentum Died at 3 days of large bronchopleural fistula Died at 4 days of large bronchopleural fistula Died at 5 days of mediastinitis Died at 5 days of mediastinitis Died at 5 days of large bronchopleural fistula

Graft status Necrotic Necrotic Necrotic Necrotic Necrotic

Group B-with omentum Died at 25 days of diaphragWelI healed; some matic incisional hernia granulation Put to death at 23 days WelI healed; some granulation Put to death at 23 days Healed; normal mucosa Put to death at 23 days Healed; normal mucosa Put to death at 23 days Healed; normal mucosa

tree up to the level of the segmental bronchi, which were divided close to their origins. The lung parenchyma was discarded. A balloon passed retrogradely through one of the opened segmental bronchi was inflated to occlude the left main bronchus. The other segmental bronchi were closed with two layers of continuous 5-0 Prolene suture to create a cul-de-sac of the bronchial tree. The left main bronchus was completely transected 1 cm proximal to its bifurcation into the lobar bronchi and then immediately reanastomosed with a continuous 5-0 Prolene suture. The occluding balloon was removed and the remaining patent segmental bronchus was sutured. The resulting bronchial autograft (Fig. 1) formed a closed stump comprising the distal 1 cm of the left main bronchus, the lobar bronchi, and the sutured origins of the segmental bronchi. On average the grafts were 2.0 em in maximum length. This model provides a totally ischemic stump of bronchus, the bronchial circulation having been interrupted at the level of transection of the left main bronchus and the pulmonary circulation having been discarded with the lung parenchyma. In Group A dogs the chest was closed at this stage; hence the only possible route for revascularization in this group was across the left main bronchial anastomosis. Omental pedicle Hap-operative technique. In Groups B and C, in addition to the bronchial autograft, the omentum was mobilized through a midline epigas-

L I. /- OM;:

/ /~'

'L

Fig. 1. Diagram demonstrating left bronchial autograft (BG) reanastomosed to the left main bronchus (LMB). The omentum (OM), with its blood supply preserved, was brought into the thorax and wrapped completely around the bronchial graft and the anastomosis.

tric incision, with care taken to preserve its vascular supply. When necessary, extra length was obtained by partially separating the omentum from its splenic attachments. With neither tension nor torsion, the omentum was brought into the left hemithorax via a 2 em opening in the left dome of the diaphragm and wrapped around the bronchial graft. Fine 5-0 Prolene sutures were used to anchor the omentum to the bronchial graft and to the edges of the diaphragmatic incision. The abdominal and thoracic incisions were then closed. Assessment of grafts. All Group A and B animals underwent postmortem evaluation after dying or being put to death at 23 days. The three Group C animals were put to death at 4, 5, and 8 days. Vascular studies. The bronchial arteries in Group A dogs were demonstrated by injection of 100 ml of a radiopaque dye (Microfil, Canton Bio-Products, Boulder, Colo.) at 100 mm Hg pressure into the descending thoracic aorta, which had been clamped above and below the origin of the bronchial vessels. In Group B and C dogs (with omentum), the celiac artery was cannulated and injected with 100 ml of dye at 100 mm Hg pressure to demonstrate the omental vessels. Following these injections the thoracic viscera were removed and the bronchial autografts inspected, pho-

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Fig. 2. ll, Group A dog (no omen tum) at 5 days. The bronchi al autograft is necrotic . Yellow dye-filled bronchial vessels are seen o nly in the proximal main bronchu s. There has been no revascu larization across the main bron chial ana stomosis. b and c . Group B dogs (with omentum) at 23 days . Viable bronchial autogra ft. In c. o mental and graft vesse ls are filled with yellow dye injec ted via a ce liac artery cannula. d. Group C (omental wrap) at 4 days. Graft mucosa is hemorrha gic and edem atous. Neovascularization via the omental vesse ls is co nfirmed by the presence of areas of yellow dye- filled vesse ls in the graft mucosa . The dye was injected into the ce liac artery.

tographed, x-rayed, and finally fixed in formalin for subsequent light micro scopy.

Results Survival (Table I). Group A. All five dogs died within 5 days of operation . Three died of a major bronchopleural fistula and two of mediastinit is.

Group B . All five dogs survived 23 days. One dog died at 25 days of a large incisional diaphragmatic hernia (the weekend preventing assessment at 23 days) and the remainder were put to death at 23 days. Graft status (Table I). Group A. All five grafts were necrotic and had patchy areas of hemorrh age and slough. Two grafts had large fistulas res ulting from breakdown of the segmen-

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tal bronchial suture line, and one had a major deh iscence of the main bronchial anastomosis . The other two grafts were infected and ,necrotic, there being gross mediastinal and pulmonary sepsis. Injection studies demonstrated the bronchial circulation down to, but not beyond , the area of the main bronchial anastomosis (Fig. 2, a) . There had been no revascularization into the bronchial grafts. Histologic examination confirmed the appearance of ischemic necrosi s (Fig. 3). Group B. All five bronchial grafts healed with no necrosis, infection , or fistula formation (Fig . 2, b ). The mucosal pattern was normal except in two graft s, in which there were small areas of erythema and granulation around several of the sutures in the main bronchial anastomosis . The bronchial walls were thickened and the graft slightly contracted in these two cases . Injection studies via the celiac artery demonstrated numerous vessels in the bronchial graft communicating with the omental circulation (Fig . 2, c and Fig. 4). Histologic examination of Group B bronchial autografts revealed normal bronchial architecture and an intact mucosa (Fig . 5). Chronic inflammatory cellular infiltrates were present , especially in those two grafts in which granulation had occurred. Group C. At 4 and 5 days the bronchial graft displayed marked mucosal edema with areas of erythema, hemorrhage , and congestion. Injection into the celiac artery demonstrated patchy areas of dye-filled vessels in the mucosa of the graft, indicating an early stage of revascularization via the omentum (Fig . 2, d). Light microscopic exam ination of 4 and 5 day grafts revealed normal architecture with scattered areas of hemorrhagic edema and congestion. There were also foci of smooth muscle and epithelial necrosis surrounded by an acute inflammatory reaction. By 8 days the mucosa appeared much more healthy , with little edema or congestion . Small areas of erythema and hemorrhage were still present. Injection studies demonstrated numerous vessels in the graft communicating with the omental arteries, indicating well-established revascularization. Histologic examination paralleled the gross appearance. Some areas of acute inflammation persisted around necrotic smooth muscle bundles; otherwise most of the mucosa was intact and the majority of the bronchial wall tissues appeared relatively normal. Discussion

The omentum posse sses a rich vascular and lymphatic network and, being mobile , it has been used in varied situations to establi sh new arterial, venous, and lymphatic communications and to promote repair in

Fig. 3. Bronchial autograft in Group A dog (no omentum) at 5 days. Complete graft necrosis with widespread cell lysis and mucosal denudation . (Hematoxylin and eosin; original magnification. x 450 . ) areas of poor healing .8- 19 In the field of pulmonary surgery , omental pedicle flaps have been successfully used in the treatment of established bronchial fistulas . Virkkula and Eerola" reported the healing of a postlobectomy fistula, and Van der Heyde , Verwers , and Van Leusen'" described the successful repair of a postpneumonectomy fistula. The bronchial autograft model used for these experiments was initially reported by Milheit and associates. " Surprisingly , they reported good autograft healing with no mortality in all II of their dogs; in contrast , all of our Group A dogs died with graft necrosis within 5 days of operation. Whatever the reasons for these differences, in our hands this model produced a severe and lethal degree of ischemia. A different free bronchial autograft model was used by Kiriluk and Merendino;" who reimplanted a I em ring of left main bronchu s in seven dogs. All seven autografts failed from ischemic necrosi s within 7 days of operation . In this study we have demonstrated the ability of the

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Fig. 4. Group B dog (with omentum) at 23 days. Roentgenograms of bronchial autograft and omental vessels filled with radiopaque contrast injected via the celiac artery. G, The graft, proximal left main bronchus, trachea, and attached omentum. b, The omentum has been removed so that the arterial pattern of the bronchial autograft can be seen.

omentum to maintain the viability of a severely ischemic bronchial autograft. Rearterialization from omentum was present on the fourth postoperative day. The graft examined at 4 days had undergone ischemic changes, many of which had resolved in the graft examined at 8 days. Although we have examined only the establishment of new arterial connections, it is likely that the venous and lymphatic circulations were similarly established via the omentum. The omental wrap also may have served as a mechanical buttress to the bronchial stump, particularly in the first 4 to 5 days, when acute ischemic changes were present and graft sutures would be subject to the stress of coughing and barking. Once revascularization was established, this risk of graft disruption would presumably decline. One dog died of an incisional diaphragmatic hernia. The risk of this complication can be minimized by using the retrostemal route for the omentum rather than the transdiaphragmatic route, and we now use the former route routinely. Several methods have been suggested previously to overcome the problem of bronchial ischemia and heal-

ing following lung transplantation. Shortening the donor bronchus ,23 telescoping the bronchial ends at the anastomosis.P' and wrapping the bronchial anastomosis with adjacent hilar tissue'" have not found successful application in human transplants. Theoretically, the most logical approach is that of re-establishing the bronchial arterial circulation by direct vascular anastomosis at the time of lung transplantation. MiIIs,26 Pinsker.F and their colleagues have demonstrated improved bronchial healing with this approach. However, the techniques involved are difficult and laborious. We anticipate that an omental pedicle flap wrapped around the bronchial anastomosis will prove to be a simpler but effective method of ensuring an adequate and early arterial circulation to the donor bronchus, while simultaneously improving lymphatic and venous drainage. We are currently evaluating the effect of omental flaps on canine lung reimplants and transplants. The problem of poor bronchial healing resulting from ischemia is not peculiar to lung transplants. In any major pulmonary resection, particularly if there has been a large preoperative dose of radiotherapy or extensive perihilar dissection, significant bronchial isch-

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Fig. 5. Bronchial autograft in Group B dog (with omentum) at 23 days. Normal architecture, including healthy mucosa, is preserved. Areas of chronic inflammatory cell infiltrate are seen. (Hematoxylin and eosin; original magnification x 450.)

emia may ensue.P In such cases in which there is concern about bronchial healing, an omental pedicle flap may be of value. Conclusion

In a severely ischemic bronchial autograft model in dogs, an omental pedicle flap established revascularization of the graft as early as the fourth postoperative day and maintained the viability of this otherwise lethal condition. We gratefully acknowledge the skilled assistance of Ms. Elaine Murphy and Miss Rita Chotai. REFERENCES Nelems JM, Rebuck AS, Cooper JD, Goldberg M, Halloran PF, Velland H: Human lung transplantation. Chest 78:569-573, 1980 2 Veith FJ, Koerner SK: Problems in the management of human lung transplant patients. Vase Surg 8:273-282, 1974

3 Pearson FG, Goldberg M, Stone RM, Colapinto RF: Bronchial arterial circulation restored after reimplantation of canine lung. Can J Surg 13:243-250, 1970 4 Andrews MJ, Pearson FG: Relation of bronchial arterial circulation and other factors to the transient defect in oxygen uptake following autotransplantation of the canine lung. Can J Surg 16:97-109, 1973 5 Rabinovich 11:Re-establishment of bronchial arteries after epxerimental lung lobe autotransplantation. J THORAC CARDIOVASC SURG 64:119-126,1972 6 Siegalman SS, Hagstrom JC, Koerner SK, Veith FJ: Restoration of bronchial artery circulation after canine lung allotransplantation. J THORAC CARDIOVASC SURG 73: 792-795, 1977 7 Lima 0, Goldberg M, Peters WJ, Ayabe H, Townsend E, Cooper JD: Bronchial omentopexy in canine lung transplantation. J THORAC CARDIOVASC SURG 83:418-421, 1982 8 Virkkula L, Eerola S: Use of omental pedicle for treatment of bronchial fistula after lower lobectomy. Scand J Thorac Cardiovasc Surg 9:287-290, 1975 9 Cort DF, Collis JL: Omental transposition in the treatment of radionecrosis. Br J Surg 60:580-582, 1973 10 Pifarre R, Hufnagel CA: Epicardiectomy and omental graft in acute myocardial infarction. Am J Surg 115: 589-593, 1968 11 Goldsmith HS, de los Santos R, Beattie EJ Jr: Omental transposition in the control of chronic lymphedema. JAMA 203:1119-1121,1968 12 Ruckley CV, Smith AM, Balfour TW: Perineal closure by omental graft. Surg Gynecol Obstet 131:300-302, 1970 13 Dupont C, Menard Y: Transposition of the greater omentum for reconstruction of the chest wall. Plast Reconstr Surg 49:263-267, 1972 14 Kiricuta J: L'utilization du grand epiploon dans de traitement des fistules post-radiotherapeutiques rectvesicovaginales et dan les cystoplasties. J Chir 89:477-484, 1965 15 Turner-Warwick RT, Wunne EJC, Handley-Ashken M: The use of the omental pedicle graft in the repair and reconstruction of the urinary tract. Br J Surg 54:849-853, 1967 16 Goldsmith JS, Kiely AA, Randal HT: Protection of intrathoracic esophageal anastomoses by omentum. Surgery 63:464-466, 1968 17 Berman EJ, Waite B, Geris EL, Bakemier RE: Omentocavopexy. Arch Surg 86:1008-1014, 1963 18 Goldsmith HS, Beattie EJ Jr: Carotid artery protection by pedicle omental wrapping. Surg Gynecol Obstet 130:5760, 1970 19 McLean DH, Buncke HJ: Autotransplant of omentum to a large scalp defect with microsurgical revascularization. Plast Reconstr Surg 49:268-274, 1972 20 Van der Heyde MN, Verwers HR, Van Leusen R: Sluiten van een lekkende bronchusnaad na pneumonectomie wegens carcinoom bij een chronische dialyse patient. Acta Chir Belg 4:271-274, 1978

2 I a Morgan et al.

21 Milheit H, Renault P, Drutel P, Chartier P, Jager P, Timsit: Contribution a la greffe pulmonaire experimentale explication de la revascularisation bronchique du greffon par I'etude d'auto-greffons bronchiques libres. Ann Chir Thorac Cardiovasc 7:1195-1201, 1969 22 Kiriluk LB, Merendino KA: An experimental evaluation of bronchial anastomosis and healing with special consideration of the plane of transection. Surg Gynecol Obstet 96: 175-182, 1953 23 Pinsker KL, Koernik SK, Kamhotz SL, Hagstrom JWC, Veith FJ: Effect of donor bronchial length on healing. J THoRAc CARDIOVASC SURG 77:669-673, 1979 24 Sinha 5BP, Dougherty JC, Boley 5J, Veith FJ: Elimination of bronchial complications in lung transplantation. Surg Forum 23:225-226, 1971

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25 Blumenstock DA, Kahn DR: Replantation and transplantation of the canine lung. J Surg Res 1:40-47, 1961 26 Mills NL, Boyd AD, Gheranpong C, Spencer FC: The significance of bronchial circulation in lung transplantation. J THoRAc CARDIOVASC SURG 60:866-878, 1970 27 Pinsker KL, Montefusco C, Kamhotz SL, Hagstrom JWC, Gliedman ML, Veith FJ: Improved bronchial anastomotic healing secondary to maintenance or restoration of bronchial arterial circulation by microsurgical techniques. Surg Forum 319:230-232, 1980 28 Pearson FG, DeLarue NC, IIves R, Todd TRJ, Cooper JD: Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J THoRAc CARDIOVASC SURG 83: I-II, 1982