The technique of unilateral double lobar lung transplantation in a canine model

OBJECTIVE: Bilateral living-donor lobar lung transplantation has become an accepted alternative to cadaveric lung transplantation. Because only one lobe is implanted in each chest cavity, this procedure seems to be best suited for children and small adults. The purpose of this study was to develop a technique of unilateral double lobar lung transplantation that can be applied to large adult patients. METHODS: Unilateral double lobar lung transplantation was performed in 6 weight-matched pairs of dogs. In donor animals the right middle, lower, and cardiac lobes were separated as a right graft, and the left lower lobe was separated as a left graft. In recipient animals these 2 grafts were implanted in the right hemithorax after right pneumonectomy. The left graft was implanted as a right upper lobe, having been rotated 180 degrees along the vertical axis and then 180 degrees along the horizontal axis. The right graft was implanted in the natural anatomic position. Function of the transplanted grafts was assessed for 3 hours after ligation of the left main pulmonary artery while the animals were ventilated with 100% oxygen. RESULTS: Morphologic adaptation of the 2 grafts in the right hemithorax was found to be excellent. All 6 animals survived the assessment period with excellent pulmonary function. At the end of the 3-hour assessment period, the arterial oxygen tension was 519 +/- 31 mm Hg, and the mean pulmonary artery pressure was 30.5 +/- 1.7 mm Hg. CONCLUSIONS: Unilateral double lobar lung transplantation was technically possible and associated with satisfactory early pulmonary function in a canine experimental model.     

Experimental study of oversized grafts in a canine living-donor lobar lung transplantation model

BACKGROUND: For infants and small children, organ transplantation is limited by the size discrepancy between donor and recipient. To address this problem, the use of over-sized grafts from living-relative donors could potentially expand the donor pool. The aim of this experimental study was to evaluate the effect of oversized grafts on early pulmonary function and to identify an indicator for acceptable size discrepancy. METHODS: Fourteen bilateral lobar lung allotransplant operations were performed without cardiopulmonary bypass in weight mismatched pairs of dogs. Animals were divided into 2 groups: Group I (n = 7), donor/recipient lung volume ratio < 2.85; Group II (n = 7), donor/recipient lung volume ratio >2.85. Pulmonary function of the recipient was measured before chest closure, after chest closure, and after the ventilator was removed. RESULTS: Pulmonary vascular resistance and airway pressure significantly increased in Group II after chest closure (1493 +/- 195 dynes sec cm(-5) and 14.4 +/- 0.9 mm Hg vs 2784 +/- 140 dynes sec cm(-5) and 23.4 +/- 1.2 mm Hg, p < 0.001). After the ventilator was removed, all recipients in Group I showed PaO2 > 239 mm Hg and PaCO2 < 76 mm Hg, whereas, all recipients in Group II showed PaO2 < 116 mm Hg and PaCO2 > 169 mm Hg. The donor/recipient chest circumference ratio was less than 1.3 in all but 1 dog in Group I. CONCLUSIONS: Acceptable, oversized grafts provide adequate pulmonary function, although excessively oversized grafts cause significant impairment in pulmonary function after chest closure. Chest circumference provides useful size-match criteria when oversized grafts are used in this canine experimental model.     

Experimental study on size matching in a canine living-donor lobar lung transplant model.

OBJECTIVE: In an effort to address the donor-shortage issue, living-donor lobar lung transplants have been performed with satisfactory results. The use of small grafts is potentially problematic because it could cause high pulmonary artery pressure, resulting in lung edema. The purpose of this study was to evaluate the effect of small grafts on early pulmonary function and to identify the predictor for acceptable size discrepancy. METHODS: Seventeen pairs of mongrel dogs with various donor-recipient sizes were used. Body weight, height, chest circumference, and lung weight were measured as size parameters. Right middle, lower, and cardiac lobes were implanted as a right lung of the recipient and the left lower lobe was implanted as a left lung without use of cardiopulmonary bypass. Pulmonary function of the recipient was measured for 6 hours after reperfusion. RESULTS: A significant negative correlation was found between donor/recipient body-weight ratio and mean pulmonary artery pressure at 1 hour (r = -0.594, P =.025). A significant correlation was found between donor/recipient body-weight ratio and PaO(2) at 6 hours (r = 0.704; P =.007). There was no significant correlation between the other 3 size parameters and postoperative pulmonary function. All 8 recipients with a donor/recipient body-weight ratio of 1.2 or greater survived the 6-hour assessment period, and their PaO(2) exceeded 500 mm Hg at 6 hours. CONCLUSIONS: Donor/recipient weight ratio is an important predictor of early pulmonary function in a canine living-donor lobar lung transplant model.     

Antibody-mediated rejection of a unilateral donor lung in bilateral living-donor lobar lung transplantation: report of a case

We report a case of antibody-mediated rejection (AMR) of a unilateral donor lung in the presence of newly formed donor-specific antibodies, 10 months after living-donor lobar lung transplantation (LDLLT). Of note is that the AMR occurred in the unilateral lung. Furthermore, the lung graft was from her husband and HLA analysis on the recipient's daughter revealed the same donor-specific HLA antigens, which strongly suggested pre-sensitization before lung transplantation. Fortunately, we could perform direct crossmatch even 1 year after lung transplantation because of the living donors.     

Suppressed erythropoiesis after ABO-minor-mismatched living-donor lobar lung transplantation.

Anti-A and/or anti-B antibodies synthesized by lymphoid tissues contained in ABO-mismatched solid organ grafts have been reported to cause hemolytic anemia, but not suppressed red blood cell production. A case of living-donor lobar lung transplantation is presented in which suppression of erythropoiesis was associated with ABO mismatched organ transplantation.     

A new technique for double lung transplantation. "Bilateral single lung" transplantation.

Two techniques are currently practiced to achieve bilateral lung transplantation for the treatment of patients with end-stage pulmonary disease associated with infection: heart-lung transplantation, which is illogical, and double lung transplantation by the Toronto technique, which is difficult and entails tracheal complications. After our short experience with single lung transplantation without any bronchial problems, we have performed three double lung transplantations by a new technique, "bilateral single lung" transplantation. After a sternal bithoracotomy, first one lung was transplanted and then the other, without cardiopulmonary bypass. This bilateral single lung transplantation provides all the advantages of single lung transplantation and is particularly recommended for use in patients with severe pleural adhesions.     

A decade of living lobar lung transplantation: recipient outcomes

OBJECTIVE: Living lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation. METHODS: One hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 +/- 7.7 years), and 39 were pediatric patients (age, 13.9 +/- 2.9 years). RESULTS: The primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients (P =.65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P =.03; Kaplan-Meier P =.002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50). CONCLUSION: These results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations.     

Pulmonary tailoring and lobar transplantation to overcome size disparities in lung transplantation

Size matching between donors and recipients represents one of the organ distribution criteria widely accepted by lung transplant teams. However, in some cases it is not possible to allocate a donor to the corresponding size-compatible recipient. To avoid possible complications derived from the implantation of oversized lungs into smaller recipients, surgical procedures such as pulmonary tailoring and lobar transplantation have been advocated. We review our experience in 13 patients undergoing volume reduction of the lung graft at the time of transplantation, either by nonanatomical lung volume reduction or by lobar transplantation. There were no significant differences between lung-downsized patients and standard lung transplantation patients in terms of donor characteristics, surgical and postoperative complications, functional outcome, and survival. We conclude that downsizing the lung graft either by nonanatomical resection or lobar transplantation is safe and reliable to overcome size disparities between donor and recipients, with no additional morbidity and with similar early and midterm outcomes to those in standard lung transplants.     

Current status of living-donor lobar lung transplantation

In living-donor lobar lung transplantation (LDLLT), 2 healthy donors donate their right or left lower lobe. Although graft size is relatively small, LDLLT provides adequate pulmonary function to the recipient. In 1998, Okayama University group reported 1st successful LDLLT in Japan. Since then, 103 clinical lung transplants have been performed in Japan. Among them 65 were LDLLT because of the difficulty in obtaining cadaveric lungs. The survival after LDLLT appears to be similar to or better than International Society for Heart and Lung Transplantation registry data on cadaveric lung transplantation. In this review, current status and problem of LDLLT are discussed.     

Referrals for lung transplantation in Japan. Unique indications and necessity of living-donor lobar lung transplantation.

OBJECTIVES: The purpose of this study was to review all referrals to our lung transplant program and to find realistic options for accepted candidates in Japan. METHODS: During the period from April 1992 to August 1999, 45 referrals were received. After screening, 22 of the referred patients were admitted for an extensive inpatient evaluation, and 15 of these were accepted as candidates for transplantation. RESULTS: The indication was primary pulmonary hypertension in 9, bronchiectasis in 2, lymphangioleiomyomatosis in 2, idiopathic pulmonary fibrosis in 1, and pneumoconiosis in the other 1. Two of those with primary pulmonary hypertension went to the USA and there received bilateral lung transplant. One with bronchiectasis received living-donor lobar lung transplantation in our center. These three recipients are alive and doing well during the follow-up period of 11 to 69 months. Among the 12 patients who have not received lung transplant, 5 patients have died while waiting. CONCLUSIONS: Indications for lung transplant are quite distinct in Japan, and primary pulmonary hypertension is the most frequent indication. Living-donor lobar lung transplantation is a realistic option for properly selected candidates.     

Growth potential of the immature transplanted lung. An experimental study

Syngeneic (Lewis to Lewis) and allogeneic (Brown Norway to Lewis) unilateral left lung transplants were performed on immature rats at 6 weeks of age at a time when alveoli are still multiplying after birth. Left lung denervation without transplantation was performed in a further group of rats (Lewis) by stripping the hilum, at 4 and 6 weeks of age. Animals were killed at either 2 weeks or 6 months after operation. Right and left lungs were analyzed separately by light microscopic quantitative techniques and findings were compared with findings from control animals matched for age and strain. The transplanted left lung in both syngeneic and allogeneic animals continued to grow to a normal size by formation of new alveoli, despite the presence of low-grade rejection activity in the immunosuppressed allogeneic group. The airways showed an increase in diameter for age at the hilum and periphery (p less than 0.01 and less than 0.001, respectively). The volume of the contralateral right lung was greater than normal because of an increase in number (p less than 0.01) and size of alveoli for age. Denervation alone was associated with normal growth of both lungs. Thus it appears that, in rats, the transplanted immature lung can fulfill its growth potential.     

Experience of the Reina Sofia hospital in lobar lung transplantation

The number of patients awaiting lung transplantation has steadily increased over the past decade, but the number of donors has remained relatively stable. Owing to the increasing scarcity of donor lungs, especially for pediatric and small adult recipients, advanced operative strategies for the use of larger grafts for smaller recipients have been developed. Size matching between donors and recipients represents one of the organ distribution criteria widely accepted by lung transplantation teams. However, in some cases it is not possible to allocate a donor to the corresponding size-compatible recipient. To avoid possible complications derived from the implantation of oversized lungs into smaller recipients, various methods of downsizing are applied for cadaveric donor lungs, such as lobar transplantation. We review our experience in 6 patients undergoing volume reduction of the lung graft by lobar resection at the time of transplantation. Graft volume reduction by anatomic resection (lobar transplantation) is a reliable and safe procedure to overcome size disparities between the donor and the recipient of a lung transplant, and thus to maximize the number of donors.     

Compensatory lung growth in autologous lobar implant: experimental study in dogs

BACKGROUND: The best way to study compensatory lung growth (CLG) is in a transplant without rejection. Since immunosuppressive drugs may influence CLG, it is better to not use them. Therefore we studied CLG in a reimplant of only one lobe after its removal. The objective was to compare lobar transplant CLG with CLG after lobectomy. METHODS: Forty eight dogs were distributed in three groups: G1 = control, G2 = left cranial lobectomy, and G3 = left pneumonectomy with reimplantation of the caudal lobe. Five months after surgery the animals underwent lung scintigraphy and were sacrificed for morphometric study. RESULTS: There was no correlation between scintigraphy and lung mass or lung volume. There was both mass and residual volume CLG in the operated groups, both contralateral and ipsilateral to surgery. There was no compensation for total lung capacity or compliance in the remaining caudal lobe (G2) or the reimplanted caudal lobe (G3) at 5 months after surgery. There was more damage in the reimplanted lobe. As previous studies have shown that CLG starts with increased mass and residual volume and compliance is compensated later. This study seemed to document the beginning of CLG, with lung compliance being the limiting factor of CLG at 5 months. CONCLUSION: There was CLG in both the reimplanted lobe and the contralateral lung, but compliance was still reduced. CLG was similar in both groups, but in the implanted lobe compliance was more prejudiced.     

A decade of living lobar lung transplantation: perioperative complications after 253 donor lobectomies.

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long-term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for >/=14 d for persistent air leaks and/or drainage. Right-sided donors were more likely to have a perioperative complication than left-sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live     

A new non-radiological method to assess potential lung recruitability: a pilot study in ALI patients

Introduction: Potentially recruitable lung has been assessed previously in patients with acute lung injury (ALI) by computed tomography. A large variability in lung recruitability was observed between patients. In this study, we assess whether a new non‐radiological bedside technique could determine potentially recruitable lung volume (PRLV) in ALI patients. Methods: Sixteen mechanically ventilated patients with early ALI/ARDS were subjected to a recruitment manoeuvre and decremental PEEP titration. Electric impedance tomography, together with measurements of end‐expiratory lung volume (EELV) and tracheal pressure, were used to determine PRLV. The method defines fully recruited open lung volume (OLV) as the volume reached at the end of two consecutive vital capacity manoeuvres to 40 cmH₂O. It also uses extrapolation of the baseline alveolar pressure/volume curve up to 40 cmH₂O, the volume reached being the non‐recruited lung volume. The difference between the fully recruited and the non‐recruited volume was defined as PRLV. Results: We observed a considerable heterogeneity among the patients in lung recruitability, PRLV range 11–47%. In a post hoc analysis, dividing the patients into two groups, a high and a low PRLV group, we found at baseline before the recruitment manoeuvre that the high PRLV group had lower compliance and a lower fraction of EELV/OLV. Conclusions: Using non‐invasive radiation‐free bedside methods, it may be possible to measure PRLV in ALI/ARDS patients. It is possible that this technique could be used to determine the need for recruitment manoeuvres and to select PEEP level on the basis of lung recruitability.