Effect of donor bronchial length on healing: a canine model to evaluate bronchial anastomotic problems in lung transplantation.

Bronchial anastomotic complications in lung transplantation in man remain a major cause of failure. To study this problem in a canine model, we varied the length of the distal bronchial component in three groups of dogs that underwent hilar stripping, bronchial transection, and reanastomosis, The distal bronchial component was thus analogous to the donor in a transplanted lung. Anastomoses were performed, respectively, at the level of the main carina (long single anastomosis), at the midpoint between the main carina and the bifurcation of the left main-stem bronchus (short single anastomosis), and just distal to the bifurcation of the left main-stem bronchus (lobar anastomosis). Bronchial anastomotic damage and necrosis were evaluated by periodic examination with a fiberoptic bronchoscope and by gross and microscopic examination at sacrifice on the seventh postoperative day. The long single anastomoses demonstrated the most necrosis, and the labor anastomoses showed the least. The short single anastomoses showed an intermediate degree of damage. These findings support the hypothesis that shortening the distal or donor bronchial component reduces anastomotic damage, probably because of better pulmonary-to-bronchial collateral blood supply. This study provides a canine model by which to examine bronchial anastomotic complicatons and demonstrates the feasibility of performing labor anastomoses as a means for decreasing bronchial anastomotic problems in lung transplantation.     

Does pleural bronchial wrapping improve wound healing in right sleeve lobectomy?

The effect of bronchial circulation on wound healing at the site of anastomosis after right upper sleeve lobectomy was studied in dogs. In two dogs (Group I), the bronchial arteries were carefully preserved during the sleeve lobectomy. In 16 dogs (Group II), only sleeve lobectomy was performed after all bronchial arteries in the hilum were ligated. In three dogs (Group III), the site of anastomosis was wrapped by a Penrose drain after sleeve lobectomy. In three other dogs (Group IV), the site of anastomosis was wrapped with a free pleural flap after sleeve lobectomy. In another group of 11 dogs (Group V), the anastomotic site was wrapped with a pedicled pleural flap. The dogs in Group I were put to death immediately and bronchial arterial circulation was recognized to consist primarily of systemic arterial blood. In Group II dogs, bronchial arteries distal to the anastomosis filled with pulmonary arterial blood immediately after the sleeve lobectomy. Although the majority of bronchial arteries became filled with systemic arterial blood with time, some vessels were filled with pulmonary arterial blood even 7 days after the sleeve lobectomy. In Group III dogs, wound healing at the site of anastomosis was severely delayed, and 7 days after the sleeve lobectomy the majority of bronchial arteries in the bronchial wall distal to the anastomosis were filled with pulmonary arterial blood. In Group IV dogs, the state of wound healing at the bronchial anastomotic site was similar to that of Group III dogs. In Group V, although the state of wound healing at the anastomosis was relatively good in most of the animals, the pedicled pleural wrap did not significantly improve bronchial circulation over that of Group II.     

Effect of omental, intercostal, and internal mammary artery pedicle wraps on bronchial healing

Bronchial transection and devascularization is necessary in the course of sleeve resection or lung transplantation, leaving distal bronchial segments ischemic and subject to stricture or dehiscence. Thirty mongrel dogs underwent left lung autotransplantation. The bronchial anastomosis was wrapped with omentum (n = 9), intercostal muscle pedicle (n = 9), or internal mammary artery pedicle grafts (n = 6). Six control animals underwent bronchial anastomosis without an external wrap. Bronchial revascularization by capillary ingrowth from the pedicle to the bronchial submucosal plexus was demonstrated with all three types of vascular pedicle grafts; however, more consistent and confluent vascular ingrowth was provided by internal mammary artery pedicle grafts. Additionally, the bronchial anastomotic cross-sectional area was significantly better in the internal mammary artery group (84.5 +/- 3.3) as compared with that of the omental (68.4 +/- 8.3), intercostal muscle (66.9 +/- 10.9), or control groups (70.2 +/- 7.6). An internal mammary artery pedicle graft and the presence of dense confluent submucosal vascular ingrowth from any pedicle graft were independently predictive (p less than 0.05) of minimizing bronchial anastomotic narrowing. These data are consistent with previous findings suggesting that omental and intercostal muscle pedicle grafts promote early bronchial revascularization; moreover, the data demonstrate the superiority of an internal mammary artery pedicle graft to provide submucosal vascular ingrowth and to minimize anastomotic stenosis.     

Peritracheal membranous adipose tissue for early revascularization of the bronchial anastomosis

The effect of a peritracheal wrap of membranous adipose tissue on revascularization of the bronchial anastomosis after left lung autotransplantation was evaluated in four groups of dogs. The bronchial anastomosis was performed just distal to the carina in groups 1 (6 dogs) and 2 (7 dogs) and as close to the lobar division as possible in groups 3 (14 dogs) and 4 (7 dogs). Peritracheal membranous adipose tissue was used in groups 1 and 3 only. The other two groups served as controls. Three dogs from group 2 had elastic Dacron fabric wrapped around the anastomotic site. Revascularization of the distal bronchus through the wrap was demonstrated in all dogs in groups 1 and 3, 7 days after surgery by postmortem injection studies but not in control groups 2 and 4, and serious bronchostenosis was also observed in the latter two groups. Histologic examination of the bronchial anastomosis revealed better structural preservation of the bronchus distal to the suture line with the adipose tissue wrap. The dogs with elastic Dacron fabric wraps showed poor structural integrity below the suture line (necrosis and calcification). Our results suggest that the level of bronchial anastomosis does not alter the healing process of the distal bronchus when a peritracheal membranous adipose tissue wrap is applied to the anastomotic site. They also indicate that the wrap is effective in restoring vascular flow across the suture line within 1 week of lung autotransplantation.     

Histologic assessment of bronchial anastomotic healing in canine lung transplantation

Postoperative wound healing of the bronchial anastomosis was studied in dogs with autotransplantation (20 dogs, 7 days to 6 years postoperatively) and allotransplantation (62 dogs, 5 to 174 days postoperatively) of the left lung. In the group undergoing lung allotransplantation, the relationship among three histologic parameters was studied: the grade of lung allograft rejection, the degree of changes in the epithelium, and submucous lymphocyte infiltration along the donor bronchus within approximately a 0.5 cm area distal to the anastomosis. In lung autotransplantation, mucosal continuity began to be observed 1 week postoperatively. Mucosal continuity and apparent collagen formation on any bronchial contiguous site were demonstrated in most animals studied more than 3 weeks postoperatively. Bronchial anastomotic healing tended to be slower in lung allotransplantation than in autotransplantation, although a mucosal continuity at the anastomosis was sporadically observed in immunosuppressed dogs surviving more than 3 weeks postoperatively with a lung allograft. There were significant rank correlations among the three histologic parameters, which showed that lung allograft rejection is closely connected with wound healing of the bronchial anastomosis in lung allotransplantation. Meticulous mucosal approximation is most necessary during bronchial anastomotic procedures. Establishment of an exact method for early monitoring of lung allograft rejection is absolutely necessary for lung allotransplantation.     

Cyclosporin and bronchial healing in canine lung transplantation

Long-term bronchial anastomotic healing has been assessed in the canine lung transplant model with cyclosporin as the primary immunosuppressant. Early bronchial revascularization was achieved by wrapping an omental pedicle around the bronchial anastomosis. Ten dogs underwent left lung transplantation and six survived 100 days or more before being put to death. No significant bronchial complications occurred. Late bronchostenosis was not seen, despite four biopsy-proved rejection episodes in three of the dogs surviving past 100 days. Histologically, all anastomoses were well healed at autopsy. Cyclosporin was shown to be an effective immunosuppressant in this model and was associated with prolonged survival and low morbidity. Transplant lung function was assessed at 100 days by contralateral pulmonary artery ligation in five dogs and was satisfactory in the three animals that had not had rejection episodes. The findings support our belief that bronchial anastomotic complications after human lung transplantation are mainly related to the effects of immunosuppression with steroids and to the ischemia resulting from division of the bronchial circulation at the time of transplantation.     

Transplantation of the left lung into the right hemithorax to facilitate immediate reconstitution of bronchial artery flow.

Immediate bronchial artery reconstitution may be important in the prevention of bronchial anastomotic problems in lung transplantation. To facilitate this reconstitution in circumstances requiring allograft replacement of the right lung, we developed a method for transplanting the left lung together with its bronchial arterial supply into the right hemithorax. With this method, left lungs were allotransplanted into the right hemithorax of nine immunosuppressed dogs. Six recipients survived 1 to 4 weeks. Death resulted from pneumonia or rejection, and there were no bronchial anastomotic problems. Roentgenograms showed that the bronchial artery was patent and that the inverted transplanted left lungs could conform exactly to the thorax without space problems or radiographic abnormalities. Except for the unusual position of the large pulmonary arteries, angiographic patterns, function, and perfusion of the transplanted lungs were often normal and equivalent to those of the recipient's normal left lung. Thus it is possible to transplant a left lung into either hemithorax and immediately reconstitute its bronchial arterial circulation. Bronchial anastomotic problems may thereby be decreased.     

Normal bronchial healing without bronchial wrapping in canine lung transplantation.

The deleterious effect of steroids on bronchial healing in lung transplantation has led to the development of techniques to protect the anastomosis and to the exclusion of steroid-dependent patients from transplantation. The effect of steroids on bronchial healing was tested in a canine single-lung allotransplantation model. Twenty size-matched mongrel dogs (20 to 30 kg) underwent left lung transplantation without anastomotic wrap or direct revascularization. Postoperatively, all received daily doses of cyclosporine (15 mg/kg) and azathioprine (1 mg/kg) and were subdivided into three steroid dosage groups. Group A (n = 10) animals received 1.5 mg/kg of prednisone per day whereas groups B (n = 5) and C (n = 5) received 5.0 mg/kg of prednisone per day for 28 postoperative days. In addition, group C received prednisone (5.0 mg.kg-1.day-1) for 1 month preoperatively. In group A, 8 of 10 dogs survived 28 days without evidence of respiratory compromise, with anastomotic bursting pressure greater than 510 mm Hg. In group B, all 5 dogs survived to 28 days without evidence of respiratory compromise and with intact bronchial anastomoses (bursting pressures greater than 510 mm Hg). In group C, 3 of 5 animals survived to 28 days with intact anastomoses. Histological examination demonstrated normal bronchial healing in all anastomoses. These data suggest that preoperative steroid dependence should not be a contraindication to lung transplantation and that bronchial anastomotic wrapping with vascular tissue may not be essential.     

Revascularization of ischemic bronchial anastomoses by an intercostal pedicle flap

Ischemia of the donor bronchus, perfused solely by retrograde collaterals from the pulmonary circulation, is an important factor in the impaired healing of the bronchial anastomosis of transplanted lungs. The healing of two experimental models of bronchial anastomotic ischemia, the bronchial segmental autograft and the postpneumonectomy bronchial autograft, was assessed in dogs. The application of a polytetrafluoroethylene wrap to the bronchial segmental autograft and the application of an intercostal pedicle flap to the postpneumonectomy bronchial autograft, with and without concomitant administration of corticosteroids, were also studied to elucidate factors that affect bronchial anastomotic healing. The bronchial segmental autograft healed normally without stricture, but isolation of this autograft from the mediastinum and lung by the polytetrafluoroethylene wrap resulted in necrosis of the autograft. All dogs that had a postpneumonectomy bronchial autograft died of bronchopleural fistulas due to autograft necrosis. Application of an intercostal pedicle flap to the autograft resulted in healing in all animals. Arteriography and Microfil injection demonstrated revascularization of the postpneumonectomy bronchial autograft by the pedicled intercostal artery. Several conclusions can be drawn: With the lung in situ the bronchial segmental autograft survives, probably as a free composite graft. In contrast, the postpneumonectomy bronchial autograft is an excellent model of bronchial anastomotic ischemia. The intercostal pedicle flap is a reliable method for providing neovascularity and mechanical reinforcement to an ischemic bronchial anastomosis. Its effect on bronchial anastomotic healing was not diminished by administration of corticosteroids. The intercostal pedicle flap may be useful in preventing bronchial anastomotic complications in clinical lung transplantation.     

Segmental nonanastomotic bronchial stenosis after lung transplantation

BACKGROUND: Nonanastomotic distal bronchial stenosis has been observed in some patients after lung transplantation. We investigated its relationship with acute cellular rejection (ACR), infection, and ischemia. METHODS: Between January 1994 and December 1997, 246 lung transplantations were performed at our hospital. These cases were retrospectively reviewed and evaluated to identify those patients with nonanastomotic bronchial stenosis. RESULTS: Six patients had bronchial stenosis within the grafted airway distal to the uninvolved anastomotic site. The average ACR before stenosis was 1.9 compared with 1.6 in a control group. ACR at the time of first recognition of the stenosis ranged from A2 to A3.5, with an average value of A2.9. All 6 patients demonstrated alloreactive airway inflammation before and at the time of stenosis. Four patients had evidence of ischemic damage in the perioperative period. CONCLUSIONS: Segmental nonanastomotic large airway stenosis after lung transplantation should be assessed separately from anastomotic complications. Although the pathogenesis is unclear, certainly one should consider alloreactive injury, ischemic damage, and infection as individual and coercive causes.     

Anatomical bases for bronchial arterial revascularization in double lung transplantation]

A study of the bronchial arterial blood supply was conducted to facilitate in surgical attempts of bronchial revascularization in double lung transplantation. This study consisted of 20 cadaveric anatomical dissections of the bronchial arterial blood supply as well as a retrospective review of 50 bronchial arteriograms. The right bronchial tree was supplied by an artery originating from the right intercostal bronchial arterial trunk in 76 to 95% of the cases. This artery also supplied the distal trachea and the carina in over 80% of cases as well as the proximal left bronchial tree via a network of small collaterals found in the subcarinal compartment and adventitial tissues located on the anterior surface of the descending aorta. A common arterial trunk for both the right and left bronchial trees was found in 12 of the 20 dissections (60%). Left bronchial arteries were much smaller and less consistent. Proximity of the bronchial arteries orifices was frequently observed: in 10 of the 20 dissections it allowed simultaneous reperfusion of more than one vessel. To maintain the vascular anastomotic network in between the right and left trees, extensive vascular dissection and carinal resections are prohibited. This will allow revascularization of the whole tracheal bronchial tree via the supply of the origin of the RICBA.     

Bronchial omentopexy in canine lung allotransplantation

Impaired bronchial healing has been a major source of morbidity and mortality following clinical lung transplantation. Bronchial ischemia secondary to division of the systemic bronchial blood supply may be an important cause of these complications. Bronchial omentopexy was performed in conjunction with lung allotransplantation in 6 dogs. Revascularization of the distal bronchial circulation through the omental pedicle was demonstrated in all instances by postmortem injection studies done through the celiac artery. Bronchostenosis occurred in 1 dog. No other complications were encountered. In view of the frequency of bronchial anastomotic complications following human lung transplantation, the technique of bronchial omentopexy warrants serious consideration.     

Catheter-in-catheter replacement technique for bronchial arterial continuous infusion therapy for pulmonary malignancies

The purpose of this study was to improve tumor effects and to reduce side effects caused by one shot bronchial arterial infusion therapy for pulmonary malignancies. The catheter-in catheter replacement technique in proper bronchial artery was introduced for infusion therapy for several hours for this purpose. Three kinds of combination of catheters were selected and the duration of replacement in bronchial artery was either eight or 24 hours. In eight patients of 12 patients with pulmonary malignancies superselective bronchial arterial infusion was carried out through the inner small catheter. No significant complications developed either at the time of replacement or during continuous infusion.     

Evaluation of a bronchial anastomosis by laser Doppler velocimetry

Healing after bronchoplasty was evaluated by assessing the bronchial mucosal blood flow by laser Doppler velocimetry in dogs. Bronchoplastic surgery at the right main bronchus was performed and bronchial mucosal blood flow was determined by laser Doppler velocimetry at proximal and distal sides of the anastomosis before and after operation. Four experimental groups were established. After operation the blood flow was adequately preserved, and healing of the anastomosis site was satisfactory in the minimum detachment group and steroid-treated group. Mucosal blood flow was markedly reduced in both proximal and distal sides in the extensive detachment group. The extent of the reduction in the blood flow was smaller in the omentum dressing group than in the extensive detachment group. The state of healing of the anastomosis site was closely related to the bronchial mucosal blood flow.     

An experimental study on direct revascularization of bronchial circulation by microvascular anastomosis.

The effects of direct revascularization of the bronchial artery after bronchoplasty were estimated by laser Doppler velocimetry and india ink injection in dogs. Bronchoplastic surgery at the right main bronchus was performed in all dogs, and the bronchial artery was reconstructed using the internal thoracic artery in the reconstruction group. The mucosal blood flow was measured at the distal side of the anastomosis. India ink was injected into the aorta in the nonreconstruction group and into the internal thoracic artery in the reconstruction group. The peripheral blood flow had diminished immediately after surgeries to 59% of the baseline value and took 14 days to recover to the baseline value in the nonreconstruction group. However, in the reconstruction group, the blood flow recovered at once to 78% of the baseline value and had returned to that value in 5 days. Statistically significant differences were noted between the groups from just after operation to day 7. India ink data confirmed these findings. In the nonreconstruction group, no ink was observed in the peripheral bronchial vessels on day 3; it was noted in part of the vessels on day 7 and in most on day 14. On the other hand, a relatively large number of vessels were stained just after operation in the reconstruction group. Thus reconstruction of the bronchial artery by means of the anastomosis with the internal thoracic artery can be said to be a useful and effective method for preventing airway ischemia.     

Coronary artery bypass grafting using side-to-side anastomosis

Recently, to obtain better long-term patency after coronary artery bypass grafting (CABG) arterial conduits such as internal mammary arteries (IMAs) and the right gastroepiploic artery have been frequently used. For coronary site anastomosis, end-to-side anastomosis is common. These conduits have a smaller diameter than the saphenous vein graft, so that, usually, longitudinal slits are made on the distal end of these grafts to obtain a more effective anastomotic orifice area. However, there is a potential for anastomotic leakage due to mismatch between the incision of the coronary artery and the arterial graft. We report here the efficacy of side-to-side anastomosis using small arterial conduits. This method has several advantages. Firstly, there is no chance of anastomotic leakage, since the coronary incision and graft incision can be perfectly matched. Secondly, if there is at least a 5-mm distance between the distal end of the graft incision and the surgical clip, the graft incision can be extended during anastomosis for adjustment. Thirdly, the distal end of the graft can be held beyond the surgical clip by forceps without damaging the arterial graft, which makes it easier for the anastomosis to be performed. Finally, the anastomosis can be checked by passing a probe through the distal end of the graft after removing the surgical clip. Also dye can be injected from the distal end of the graft at "Off Pump CABG", intraoperatively. This technique can be applied not only for distal end anastomosis, but also for proximal end, using free IMA to the ascending aorta and to make a Y-graft.     

Usefulness of sequential bypass technique in arterial reconstruction

Although sequential bypass grafting has been recommended for surgical treatment of lower limb ischemia in patients with complex multisegmental arterial occlusion, hemodynamic evaluation of the sequential bypass procedure remains to be resolved. The present study was undertaken to evaluate the sequential bypass operation to assess its usefulness from the standpoint of hemodynamics. A model was made simulating a sequential bypass in the mongrel dogs, and blood flow through the sequential bypass graft much more increased than through the standard one, measured by an electromagnetic flowmeter. By flow visualization in a glass tube model, type of flow separation and stagnation region in case of a side-to-side anastomosis was similar to those in case of an end-to-side one. The stagnation area at the anastomotic site was widened when the vascular resistance increased in the ramified vessel which corresponded to the host distal artery. It was considered reasonable to blockade the retrograde blood flow through the anastomotic site by ligating the host artery proximal to the anastomotic point when the retrograde blood perfusion was unnecessary. Clinical results of 21 cases with the sequential bypass grafting were presented and the usefulness of the technique was discussed from a hemodynamic viewpoint.     

Steroids and immunosuppression. Effect on anastomotic intimal hyperplasia in femoral arterial dacron bypass grafts.

The effects of steroids and immunosuppression on 6-cm long bilateral femoral arterial Dacron bypass grafts were studied in 30 adult mongrel dogs. The dogs were serially placed into one of the following three groups: control, steroid, and immunosuppression. The control and steroid groups each had a 70% graft patency rate, whereas the immunosuppression group had a 100% eight-week graft patency rate. The results in the steroid group were not statistically different from the control group, whereas the results in the immunosuppression group were statistically different from the control. The decrease in internal diameter was secondary to a localized accumulation of tissue at the anastomotic site, which histologically appeared to be a hyperplastic intima morphologically different in each group. There is a substantial decrease in intimal hyperplasia at anastomotic sites and a higher graft patency rate in dogs treated with low-dose azathioprine as compared with control of steroid-treated animals. The mechanism seems to be a slower and more orderly intimalization rather than suppression of any specific intimal cellular elements.     

Restoration of bronchial artery circulation after canine lung allotransplantation.

To evaluate the re-establishment of the bronchial circulation in lung transplantation, we studied 10 immunosuppressed dogs up to 14 weeks after left lung allografting. Selective in vivo bronchial arteriograms were performed repetitively via the transfemoral route. In the early postoperative period, no fillinf og vessels distal of the bronchial anastomosis could be shown. After 12 days, however, continuity of the bronchial arteries across the anastomosis was present, and dye-filled ramifications of these vessels were visualized on the secondary and tertiary bronchi. Reconstitution of the bronchial circulation was also confirmed by postmortem studies after injecting the isolated descending thorasis aorta with colored radiopaque material (microfil). The bronchial mucosa at autopsy was examined microscopically. There was no correlation between its viability and bronchial artery regeneration. Although early ischemia of the transplant bronchus may be after a factor in the bronchial complcations that follow lung transplantation, the present study indicates that this ischemia is not due to failure of bronchial artery regeneration.