J THoRAc CARDIOVASC SURG 89:872-876, 1985 Combined heart-lung transplantation for terminal pulmonary lymphangioleiomyomatosis Combined heart-lungtransplantation withcyclosporine is reported in a 26-year-old patient who presented with end-stage pulmonary Iymphangioleiomyomatosis. The operation was successful and the patient's rehabilitation excellentover the first 7 postoperative months.She then developed obliterative bronchiolitis of unknown origin. To our knowledge, this is the first published report of an out-hospital survival after heart-lung transplantation for terminal nonvascular lung disease. F. Wellens, M.D., M. Estenne, M.D., P. de Francquen, M.D., J. Goldstein, M.D., J. L. Leclerc, M.D., and G. Primo, M.D., Brussels, Belgium Human heart-lung transplantation was begun at Stanford in March, 1981, after extensive experience with orthotopic human heart transplantation 1,2 and excellent long-term animal results with heart-lung trans- plantation.v' Unilateral lung transplantation is complicated by difficulty in diagnosis of rejection, bronchial healing, infection from the contralateral lung, and perfusion- ventilation imbalance.' The first clinical results obtained with a simplified surgical technique of en bloc heart- lung transplantation and with cyclosporine as the prin- cipal immunosuppressive drug suggest that these com- plications can be minimized." The initial clinical trial of heart-lung transplantation has been for patients with end-stage pulmonary vascular disease'< (primary pulmonary hypertension and Eisen- menger's syndrome). Only two attempts of heart-lung transplantation for nonvascular pulmonary disease have been previously reported, and in each case without any out-of-hospital survival.' Cardiac transplantation was restarted in our depart- ment in 1981. The first patient admitted for combined heart-lung transplantation presented with terminal pul- From the Department of Cardiac Surgery. Department of Thoracic Surgery and Chest Department, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium. Dr. Estenne was a recipient of a fellowship from the Erasme Foundation. Received for publication May 14, 1984. Accepted for publication Aug. 15, 1984. Address for reprints: Prof. G. Primo, Department of Cardiac Surgery, Hopital Erasme, Route de Lennik, 808, 1070 Brussels, Belgium. 872 Fig. 1. Posteroanterior roentgenogram of the 23-year-old female donor. monary failure because of lymphangioleiomyomatosis.' Her clinical evolution and successful surgical treatment form the basis of this report." Case report A 24-year-old white woman was seen in the pulmonary outpatient clinic in December, 1981, because of worsening exertional dyspnea and recurrent hemoptysis of 2 years' duration. Results of her physical examination were normal apart from thoracic enlargement owing to pulmonary hyperin- flation and peripheral cyanosis. The chest roentgenogram and pulmonary function studies (Table I) revealed features sugges-
Combined heart-lung transplantation for terminal pulmonary lymphangioleiomyomatosis
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Combined heart-lung transplantation for terminal pulmonary lymphangioleiomyomatosisCombined heart-lung transplantation withcyclosporine is reported in a 26-year-old patient whopresented with end-stage pulmonary Iymphangioleiomyomatosis. The operation was successful and the patient's rehabilitationexcellentoverthe first 7 postoperative months.She then developed obliterative bronchiolitis of unknown origin. To our knowledge, this is the first published report of an out-hospital survival after heart-lung transplantation for terminal nonvascular lung disease.
F. Wellens, M.D., M. Estenne, M.D., P. de Francquen, M.D., J. Goldstein, M.D., J. L. Leclerc, M.D., and G. Primo, M.D., Brussels, Belgium
Human heart-lung transplantation was begun at Stanford in March, 1981, after extensive experience with orthotopic human heart transplantation1,2 and excellent long-term animal results with heart-lung trans plantation.v'
Unilateral lung transplantation is complicated by difficulty in diagnosis of rejection, bronchial healing, infection from the contralateral lung, and perfusion ventilation imbalance.' The first clinical results obtained with a simplified surgical technique of en bloc heart lung transplantation and with cyclosporine as the prin cipal immunosuppressive drug suggest that these com plications can be minimized."
The initial clinical trial of heart-lung transplantation has been for patients with end-stage pulmonary vascular disease'< (primary pulmonary hypertension and Eisen menger's syndrome). Only two attempts of heart-lung transplantation for nonvascular pulmonary disease have been previously reported, and in each case without any out-of-hospital survival.'
Cardiac transplantation was restarted in our depart ment in 1981. The first patient admitted for combined heart-lung transplantation presented with terminal pul-
From the Department of Cardiac Surgery. Department of Thoracic Surgery and Chest Department, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium.
Dr. Estenne was a recipient of a fellowship from the Erasme Foundation.
Received for publication May 14, 1984.
Accepted for publication Aug. 15, 1984.
Address for reprints: Prof. G. Primo, Department of Cardiac Surgery, Hopital Erasme, Route de Lennik, 808, 1070 Brussels, Belgium.
872
Case report
A 24-year-old white woman was seen in the pulmonary outpatient clinic in December, 1981, because of worsening exertional dyspnea and recurrent hemoptysis of 2 years' duration. Results of her physical examination were normal apart from thoracic enlargement owing to pulmonary hyperin flation and peripheral cyanosis. The chest roentgenogram and pulmonary function studies (Table I) revealed features sugges-
Volume 89
Heart-lung transplantation 8 7 3
Fig. 2. Preoperative chest roentgenograms of the heart-lung recipient. Note the signs of hyperinflation.
Table I. Respiratory function studies in a patient with lymphangioleiomyomatosis before and after combined heart-lung transplantation
Before transplantation After transplantation
Variable Predicted Jan.. 1982 I July. 1983 Oct.. 1983 I Jan .. 1984 I May, 1984
VC (L) FRC (L)
RV (L) TLC (L) FEV I (L) FEVJ, VC (%) TCO (rnmol/sec/Kl'a) Pao, (mm Hg)
Paco, (mm Hg)
74.3 0.173
100 40
38.8 0.071
51 31
25.6 0.019
47 31
90 0.062
90 39
78.7 0.085
93 39
41 0.085
74 37
Legend: YC. Vital capacity. FRC. Functional residual capacity. RY. Residual volume. TLC. Total lung capacity. FEY1• Forced expiratory volume in I second. TeO. Carbon monoxide diffusing capacity. Pao" Arterial partial pressure of oxygen at rest. Paco" Arterial partial pressure of carbon dioxide.
tive of lymphangioleiomyomatosis." This diagnosis was con firmed by open lung biopsy. Even though analysis of lung tissue revealed no estrogen or progesterone receptors, a 9 month course of hormonal therapy was attempted with first 400 mg and then 800 mg of intramuscular medroxyprogeste rone acetate per month." The treatment did not alter the progression of the disease, and prednisolone was instituted in November, 1982, with no benefit. From January to May,
1983, her condition markedly worsened as demonstrated by deterioration of the pulmonary function tests (Table I), and she became virtually chairbound. Between May and August, 1983, she developed a right chylothorax and three episodes of unilateral pneumothorax for which she was treated by tube thoracostomy.
On Aug. 24, 1983, a 23-year-old female donor became available. The donor had sustained severe cranial trauma and
8 7 4 Wellens et al.
Fig. 3. Chest roentgenogram 5 months after heart-lung transplantation.
was declared brain dead after she had been ventilated for 20 hours. The chest x-ray film was clear (Fig. 1) and gas exchange was within normal limits. Body size and surface area were approximately equal to those of the recipient, except for the discrepancy in thoracic cage circumference because of the recipient's hyperinflation (Fig. 2).
The operative technique for both donor and recipient was as described by the Stanford group." The heart was protected with intra-aortic infusion of 1,000 ml of cold hyperkalemic cardioplegic solution and the lungs with intrapulmonary perfusion of 1,500 ml of Ringer's lactate together with extensive topical cooling. At operation the recipient's lungs were greatly hyperinflated and completely filled the anterior mediastinum. Therefore, cardiopulmonary bypass was initially instituted with a single 32 Fr. cannula in the right atrial appendage and an aortic cannula in the high ascending aorta. This particular procedure succeeded in reducing both cardiac and lung volumes, which allowed easier subsequent standard bicaval cannulation.
A 2 L chylous effusion was evacuated from the right hemithorax after separate organ excision. In the posterior mediastinum several large lymphatic vessels were controlled. Anastomosis of the trachea was performed with a running 3-0 Prolene suture and anastomosis of the right atrium and ascending aorta with a running 4-0 Prolene suture. The patient was easily weaned from cardiopulmonary bypass. Reoperation for bleeding was necessary 4 hours postoperatively, and a residual bronchial vessel in the posterior mediastinum was controlled. Extubation was possible 18 hours after operation. In the first postoperative days, periods of marked bradypnea accompanied by carbon dioxide retention up to 54 mm Hg were observed.
The Journal of
Thoracic and Cardiovascular
Surgery
Immunosuppression consisted in cyclosporine (12 rug/kg/day) and azathioprine (1.5 mg/kg/day) for the first 2 weeks. No antithymocyte globulin was given. Corticosteroids were discontinued after a starting dose of 1.5 gm of intrave nous methylprednisolone during the first 36 hours. On postop erative day 16 azathioprine was replaced by oral prednisoneat a maintenance dose' of 0.4 mg/kg/day, progressively tapered down to 0.2 m/kg/day. The postoperative course was relative ly smooth, except for persistent fever from day 8 until day 28 because of a localized wound infection and a small anterior mediastinal abscess. The responsible pathogen was Escheri chia coli, which was also cultured from the donor's tracheal secretions and from the postoperative pleural liquid. Local surgical debriding and intravenous administration of ampicil lin and gentamycin for 18 days completely resolved this infectious complication.
Endomyocardial biopsy specimens obtained at weekly inter vals provided no sign of rejection. Renal and hepatic function remained normal. Cyclosporine levels were closely monitored and adapted daily so as to maintain serum concentrations between 100 and 250 ng/rnl.
Serial chest x-ray films showed moderate intrapulmonary lymphatic stasis during the first 3 weeks, which resolved spontaneously except for a left chylothorax that was evacuated by needle aspiration on postoperative day 12. A small bilateral apical pneumothorax was present during the first 10 days. There were no neurological sequelae, apart from a transient motor paralysis of the left brachial plexus.
The patient was discharged on postoperative day 45. Blood gases and the chest roentgenogram at that time were within normal limits (Table I and Fig. 3). Between October, 1983, and April, 1984, the patient's clinical status remained excellent and her lifestyle was normal, including high altitude skiing. In April, 1984, she begun to complain again of exertional dyspnea without hemoptysis or any other symptom. The chest roentgenogram was still within normal limits, but respiratory function studies showed clear-cut deterioration. Table I illus trates that during the first postoperative months static lung volumes and carbon monoxide diffusing capacity were some what reduced but airway mechanics was within normal limits. Pulmonary function tests performed in May, 1984, showed rapidly increasing airway obstruction without significant change in carbon monoxide diffusing capacity. Because it was crucial to establish a correct diagnosis, an open lung biopsy was performed in June, 1984. The biopsy specimen displayed no feature suggestive of pulmonary lymphangioleiomyomato sis. The bronchioles showed mural fibrosis and slight infiltra tion with mononuclear inflammatory cells, which markedly narrowed the airway lumen. The alveolar spaces and interal veolar septa were normal. These changes are those of obliter ative bronchiolitis.
Discussion
This case report supports the suggestion of Jamieson and associates" that combined heart-lung transplanta tion with cyclosporine as the main immunosuppressive medication may be a suitable treatment for patients with end-stage nonvascular pulmonary disease. It also confirms that, unlike the situation with unilateral lung transplantation with cyclosporine,1I major ventilation perfusion imbalance and pulmonary infections from the
Volume 89
Number 6
June, 1985
contralateral lung are avoided. One of our major concerns was the relative disparity between the recipi ent's enlarged thoracic cage and the donor's lung size. Most heart-lung transplantations previously performed have been done in patients with normal or reduced lung volumes. In our patient, exposure of the right atrium and dissectionof each lung were very impractical because of the hyperinflation and markedly disturbed the hemody namic status.
Early institution of cardiopulmonary bypass with singlevenous cannulation via the right atrial appendage appeared to be effective in reducing both cardiac and lung volumes and made subsequent standard bicaval cannulation and organ removal easier and safer. Postop eratively, a bilateral apical pneumothorax was present, but it did not affect the restitution of normal gas exchange and it resolved spontaneously. Thus the pres ence of an enlarged thoracic cage in the recipient appears to have no major adverse effect on the postop erative course, and combined heart-lung transplantation might be considered in other hyperinflated lung diseases such as emphysema.
We have no clear-cut explanation for the bradypnea and moderate carbon dioxide retention observed during the first 2 postoperative days. Possible mechanisms include removal of the vagal afferent nerves from the lungs and airways. That the ventilatory response to carbon dioxide is profoundly affected in vagus-blocked human beings has been well documented." Although a possible mechanism, this theory is purely speculative and must be substantiated by further studies of the control of breathing in the early postoperative period.
Postoperative interstitial pulmonary edema was limit ed and without clinical implication. This is in sharp contrast with the experience of the Stanford group, 13
which reported a reimplantation response in each patient. We believe that this difference might be attrib uted, at least in part, to the absence of any postoperative volume overload in our young patient because of the normal preoperative cardiac and postoperative renal function.
After more than 7 postoperative months with excel lent rehabilitation, the patient exhibited physiological and morphological abnormalities suggestive of oblitera tive bronchiolitis.14. 15 To our knowledge, this late postop erative complication has never been reported previously after human heart or heart-lung transplantation. Oblit erative bronchiolitis may be related to infection, usually viral, or to exposure to toxic fumes, but it is often of unknown cause. Obviously, viral infection involving the lung is a frequent occurrence in immunosuppressed patients; alternatively, ischemic damage to the bronchi
Heart-lung transplantation 875
or chronic rejection might also be implicated after heart-lung transplantation.
In conclusion, the present case report indicates that the simplified surgical technique of en bloc heart-lung transplantation can be successfully applied to patients with nonvascular lung disease and thoracic enlargement. However, to the extent that the course of obliterative bronchiolitis may be static or progressively downhill, the long-term evolution of the disease in our patient has yet to be determined.
REFERENCES
Pennock JL, Oyer PE, Reitz BA, Jamieson SW, Bieber CP, Wallwork JL, Stinson EB, Shumway NE: Cardiac transplantation in perspective for the future. J THORAC CARDIOVASC SURa 83: 168-177, 1982
2 Reitz BA, Wallwork JL, Hunt SA, Pennock JL, Billing ham ME, Oyer PE, Stinson EB, Shumway NE: Heart lung transplantation. Successful therapy for patients with pulmonary vascular disease. N Engl J Med 306:557-564, 1982
3 Reitz BA, Burton NA, Jamieson SW, Bieber CP, Pennock JL, Stinson EB, Shumway NE: Heart and lung transplan tation: Autotransplantation and allotransplantation in pri mates with extended survival. J THORAC CARDIOVASC SURa 80:360-372, 1980
4 Reitz BA, Pennock JL, Sliumway NE: Simplified opera tive method for heart and lung transplantation. J Surg Res 31: 1-5, 1981
5 Van der Hoeft Pl, Rocmans P, Nemry C, de Francquen P, Lauvau N, Pector JC: Left lung transplantation in a patient with emphysema. Arch Surg 103:505-509, 1971
6 Jamieson SW, Reitz BA, Oyer PE, Billingham ME, Modry D, Baldwin J, Stinson EB, Hunt SA, Theodore r, Bieber CP, Shumway NE: Combined heart and lung transplantation. Lancet 1:1930-1931,1983
7 Sabiston DC, Spencer FC: Gibbon's Surgery of the Chest, ed 3, Philadelphia, 1976, W. B. Saunders Company, pp 1491-1506
8 Carrington CB, Cugell DW, Gaensler EA, Marks A, Redding RA, Schaaf ]T, Tomasian A: Lyrnphangioleio myomatosis. Physiologic-pathologic-radiologic correla tions. Am Rev Respir Dis 116:977-995, 1977
9 Estenne M, de Francquen P, Wellens F, Leclerc JL, Van der Hoeft P, Yernault JC, Primo G: Combined heart and lung transplantation for Iymphangioleiomyomatosis. Lan cet 1:275, 1984
10 McCarty KS Jr, Mossier JA, McLelland R, Sieker MO: Pulmonary Iyrnphagioleiomyomatosis responsive to pro gesterone. N Engl J Med 303:1461-1465, 1980
11 Kamholz SL, Veith FJ, Mollenkopf FP, Pinsker KL, Kaleya RR, Norin AJ, Gleedman ML, Emeson EE, Merav AD, Brodman R, Fell SC, Sheldon M, Montefusco CM: Single lung transplantation with cyclosporin immu nosuppression. J THORAC CARDIOVASC SURa 86:537-542, 1983
8 7 6 Wellens et al.
12 Guz A, Noble MI, Widdicombe JG: The effect of bilateral block of vagus and glossopharyngeal nerves on the ventila tory response to CO 2 of conscious man. Resp Physiol 1:206-210, 1966
13 Reitz BA, Gaudiana VA, Hunt SA, Wallwork J, Billing ham ME, Oyer PE, Baumgarter WA, Jamieson SW, Stinson EB, Shumway NE: Diagnosis and treatment of
Bound volumes available to subscribers
The Journal of
Thoracic and Cardiovascular
allograft rejection in heart-lung recipients. J THoRAe CARDIOVASC SURG 85:354-361, 1983
14 Wohl MEB, Chernick V: State of the art. Bronchiolitis. Am Rev Respir Dis 118:759-780, 1978
15 Editorial: Obliterative bronchiolitis. Lancet 1:603-604, 1982
Bound volumes of THE JOURNAL OFTHORACIC AND CARDIOVASCULAR SURGERY are available to subscribers (only) for the 1985 issues from the Publisher, at a cost of $61.45 ($77.10 international) for Vol. 89 (January-June) and Vol. 90 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 30 days after publication of the last issue of the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis, Missouri 63146, USA; phone (800) 325-4177, ext. 351.
F. Wellens, M.D., M. Estenne, M.D., P. de Francquen, M.D., J. Goldstein, M.D., J. L. Leclerc, M.D., and G. Primo, M.D., Brussels, Belgium
Human heart-lung transplantation was begun at Stanford in March, 1981, after extensive experience with orthotopic human heart transplantation1,2 and excellent long-term animal results with heart-lung trans plantation.v'
Unilateral lung transplantation is complicated by difficulty in diagnosis of rejection, bronchial healing, infection from the contralateral lung, and perfusion ventilation imbalance.' The first clinical results obtained with a simplified surgical technique of en bloc heart lung transplantation and with cyclosporine as the prin cipal immunosuppressive drug suggest that these com plications can be minimized."
The initial clinical trial of heart-lung transplantation has been for patients with end-stage pulmonary vascular disease'< (primary pulmonary hypertension and Eisen menger's syndrome). Only two attempts of heart-lung transplantation for nonvascular pulmonary disease have been previously reported, and in each case without any out-of-hospital survival.'
Cardiac transplantation was restarted in our depart ment in 1981. The first patient admitted for combined heart-lung transplantation presented with terminal pul-
From the Department of Cardiac Surgery. Department of Thoracic Surgery and Chest Department, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium.
Dr. Estenne was a recipient of a fellowship from the Erasme Foundation.
Received for publication May 14, 1984.
Accepted for publication Aug. 15, 1984.
Address for reprints: Prof. G. Primo, Department of Cardiac Surgery, Hopital Erasme, Route de Lennik, 808, 1070 Brussels, Belgium.
872
Case report
A 24-year-old white woman was seen in the pulmonary outpatient clinic in December, 1981, because of worsening exertional dyspnea and recurrent hemoptysis of 2 years' duration. Results of her physical examination were normal apart from thoracic enlargement owing to pulmonary hyperin flation and peripheral cyanosis. The chest roentgenogram and pulmonary function studies (Table I) revealed features sugges-
Volume 89
Heart-lung transplantation 8 7 3
Fig. 2. Preoperative chest roentgenograms of the heart-lung recipient. Note the signs of hyperinflation.
Table I. Respiratory function studies in a patient with lymphangioleiomyomatosis before and after combined heart-lung transplantation
Before transplantation After transplantation
Variable Predicted Jan.. 1982 I July. 1983 Oct.. 1983 I Jan .. 1984 I May, 1984
VC (L) FRC (L)
RV (L) TLC (L) FEV I (L) FEVJ, VC (%) TCO (rnmol/sec/Kl'a) Pao, (mm Hg)
Paco, (mm Hg)
74.3 0.173
100 40
38.8 0.071
51 31
25.6 0.019
47 31
90 0.062
90 39
78.7 0.085
93 39
41 0.085
74 37
Legend: YC. Vital capacity. FRC. Functional residual capacity. RY. Residual volume. TLC. Total lung capacity. FEY1• Forced expiratory volume in I second. TeO. Carbon monoxide diffusing capacity. Pao" Arterial partial pressure of oxygen at rest. Paco" Arterial partial pressure of carbon dioxide.
tive of lymphangioleiomyomatosis." This diagnosis was con firmed by open lung biopsy. Even though analysis of lung tissue revealed no estrogen or progesterone receptors, a 9 month course of hormonal therapy was attempted with first 400 mg and then 800 mg of intramuscular medroxyprogeste rone acetate per month." The treatment did not alter the progression of the disease, and prednisolone was instituted in November, 1982, with no benefit. From January to May,
1983, her condition markedly worsened as demonstrated by deterioration of the pulmonary function tests (Table I), and she became virtually chairbound. Between May and August, 1983, she developed a right chylothorax and three episodes of unilateral pneumothorax for which she was treated by tube thoracostomy.
On Aug. 24, 1983, a 23-year-old female donor became available. The donor had sustained severe cranial trauma and
8 7 4 Wellens et al.
Fig. 3. Chest roentgenogram 5 months after heart-lung transplantation.
was declared brain dead after she had been ventilated for 20 hours. The chest x-ray film was clear (Fig. 1) and gas exchange was within normal limits. Body size and surface area were approximately equal to those of the recipient, except for the discrepancy in thoracic cage circumference because of the recipient's hyperinflation (Fig. 2).
The operative technique for both donor and recipient was as described by the Stanford group." The heart was protected with intra-aortic infusion of 1,000 ml of cold hyperkalemic cardioplegic solution and the lungs with intrapulmonary perfusion of 1,500 ml of Ringer's lactate together with extensive topical cooling. At operation the recipient's lungs were greatly hyperinflated and completely filled the anterior mediastinum. Therefore, cardiopulmonary bypass was initially instituted with a single 32 Fr. cannula in the right atrial appendage and an aortic cannula in the high ascending aorta. This particular procedure succeeded in reducing both cardiac and lung volumes, which allowed easier subsequent standard bicaval cannulation.
A 2 L chylous effusion was evacuated from the right hemithorax after separate organ excision. In the posterior mediastinum several large lymphatic vessels were controlled. Anastomosis of the trachea was performed with a running 3-0 Prolene suture and anastomosis of the right atrium and ascending aorta with a running 4-0 Prolene suture. The patient was easily weaned from cardiopulmonary bypass. Reoperation for bleeding was necessary 4 hours postoperatively, and a residual bronchial vessel in the posterior mediastinum was controlled. Extubation was possible 18 hours after operation. In the first postoperative days, periods of marked bradypnea accompanied by carbon dioxide retention up to 54 mm Hg were observed.
The Journal of
Thoracic and Cardiovascular
Surgery
Immunosuppression consisted in cyclosporine (12 rug/kg/day) and azathioprine (1.5 mg/kg/day) for the first 2 weeks. No antithymocyte globulin was given. Corticosteroids were discontinued after a starting dose of 1.5 gm of intrave nous methylprednisolone during the first 36 hours. On postop erative day 16 azathioprine was replaced by oral prednisoneat a maintenance dose' of 0.4 mg/kg/day, progressively tapered down to 0.2 m/kg/day. The postoperative course was relative ly smooth, except for persistent fever from day 8 until day 28 because of a localized wound infection and a small anterior mediastinal abscess. The responsible pathogen was Escheri chia coli, which was also cultured from the donor's tracheal secretions and from the postoperative pleural liquid. Local surgical debriding and intravenous administration of ampicil lin and gentamycin for 18 days completely resolved this infectious complication.
Endomyocardial biopsy specimens obtained at weekly inter vals provided no sign of rejection. Renal and hepatic function remained normal. Cyclosporine levels were closely monitored and adapted daily so as to maintain serum concentrations between 100 and 250 ng/rnl.
Serial chest x-ray films showed moderate intrapulmonary lymphatic stasis during the first 3 weeks, which resolved spontaneously except for a left chylothorax that was evacuated by needle aspiration on postoperative day 12. A small bilateral apical pneumothorax was present during the first 10 days. There were no neurological sequelae, apart from a transient motor paralysis of the left brachial plexus.
The patient was discharged on postoperative day 45. Blood gases and the chest roentgenogram at that time were within normal limits (Table I and Fig. 3). Between October, 1983, and April, 1984, the patient's clinical status remained excellent and her lifestyle was normal, including high altitude skiing. In April, 1984, she begun to complain again of exertional dyspnea without hemoptysis or any other symptom. The chest roentgenogram was still within normal limits, but respiratory function studies showed clear-cut deterioration. Table I illus trates that during the first postoperative months static lung volumes and carbon monoxide diffusing capacity were some what reduced but airway mechanics was within normal limits. Pulmonary function tests performed in May, 1984, showed rapidly increasing airway obstruction without significant change in carbon monoxide diffusing capacity. Because it was crucial to establish a correct diagnosis, an open lung biopsy was performed in June, 1984. The biopsy specimen displayed no feature suggestive of pulmonary lymphangioleiomyomato sis. The bronchioles showed mural fibrosis and slight infiltra tion with mononuclear inflammatory cells, which markedly narrowed the airway lumen. The alveolar spaces and interal veolar septa were normal. These changes are those of obliter ative bronchiolitis.
Discussion
This case report supports the suggestion of Jamieson and associates" that combined heart-lung transplanta tion with cyclosporine as the main immunosuppressive medication may be a suitable treatment for patients with end-stage nonvascular pulmonary disease. It also confirms that, unlike the situation with unilateral lung transplantation with cyclosporine,1I major ventilation perfusion imbalance and pulmonary infections from the
Volume 89
Number 6
June, 1985
contralateral lung are avoided. One of our major concerns was the relative disparity between the recipi ent's enlarged thoracic cage and the donor's lung size. Most heart-lung transplantations previously performed have been done in patients with normal or reduced lung volumes. In our patient, exposure of the right atrium and dissectionof each lung were very impractical because of the hyperinflation and markedly disturbed the hemody namic status.
Early institution of cardiopulmonary bypass with singlevenous cannulation via the right atrial appendage appeared to be effective in reducing both cardiac and lung volumes and made subsequent standard bicaval cannulation and organ removal easier and safer. Postop eratively, a bilateral apical pneumothorax was present, but it did not affect the restitution of normal gas exchange and it resolved spontaneously. Thus the pres ence of an enlarged thoracic cage in the recipient appears to have no major adverse effect on the postop erative course, and combined heart-lung transplantation might be considered in other hyperinflated lung diseases such as emphysema.
We have no clear-cut explanation for the bradypnea and moderate carbon dioxide retention observed during the first 2 postoperative days. Possible mechanisms include removal of the vagal afferent nerves from the lungs and airways. That the ventilatory response to carbon dioxide is profoundly affected in vagus-blocked human beings has been well documented." Although a possible mechanism, this theory is purely speculative and must be substantiated by further studies of the control of breathing in the early postoperative period.
Postoperative interstitial pulmonary edema was limit ed and without clinical implication. This is in sharp contrast with the experience of the Stanford group, 13
which reported a reimplantation response in each patient. We believe that this difference might be attrib uted, at least in part, to the absence of any postoperative volume overload in our young patient because of the normal preoperative cardiac and postoperative renal function.
After more than 7 postoperative months with excel lent rehabilitation, the patient exhibited physiological and morphological abnormalities suggestive of oblitera tive bronchiolitis.14. 15 To our knowledge, this late postop erative complication has never been reported previously after human heart or heart-lung transplantation. Oblit erative bronchiolitis may be related to infection, usually viral, or to exposure to toxic fumes, but it is often of unknown cause. Obviously, viral infection involving the lung is a frequent occurrence in immunosuppressed patients; alternatively, ischemic damage to the bronchi
Heart-lung transplantation 875
or chronic rejection might also be implicated after heart-lung transplantation.
In conclusion, the present case report indicates that the simplified surgical technique of en bloc heart-lung transplantation can be successfully applied to patients with nonvascular lung disease and thoracic enlargement. However, to the extent that the course of obliterative bronchiolitis may be static or progressively downhill, the long-term evolution of the disease in our patient has yet to be determined.
REFERENCES
Pennock JL, Oyer PE, Reitz BA, Jamieson SW, Bieber CP, Wallwork JL, Stinson EB, Shumway NE: Cardiac transplantation in perspective for the future. J THORAC CARDIOVASC SURa 83: 168-177, 1982
2 Reitz BA, Wallwork JL, Hunt SA, Pennock JL, Billing ham ME, Oyer PE, Stinson EB, Shumway NE: Heart lung transplantation. Successful therapy for patients with pulmonary vascular disease. N Engl J Med 306:557-564, 1982
3 Reitz BA, Burton NA, Jamieson SW, Bieber CP, Pennock JL, Stinson EB, Shumway NE: Heart and lung transplan tation: Autotransplantation and allotransplantation in pri mates with extended survival. J THORAC CARDIOVASC SURa 80:360-372, 1980
4 Reitz BA, Pennock JL, Sliumway NE: Simplified opera tive method for heart and lung transplantation. J Surg Res 31: 1-5, 1981
5 Van der Hoeft Pl, Rocmans P, Nemry C, de Francquen P, Lauvau N, Pector JC: Left lung transplantation in a patient with emphysema. Arch Surg 103:505-509, 1971
6 Jamieson SW, Reitz BA, Oyer PE, Billingham ME, Modry D, Baldwin J, Stinson EB, Hunt SA, Theodore r, Bieber CP, Shumway NE: Combined heart and lung transplantation. Lancet 1:1930-1931,1983
7 Sabiston DC, Spencer FC: Gibbon's Surgery of the Chest, ed 3, Philadelphia, 1976, W. B. Saunders Company, pp 1491-1506
8 Carrington CB, Cugell DW, Gaensler EA, Marks A, Redding RA, Schaaf ]T, Tomasian A: Lyrnphangioleio myomatosis. Physiologic-pathologic-radiologic correla tions. Am Rev Respir Dis 116:977-995, 1977
9 Estenne M, de Francquen P, Wellens F, Leclerc JL, Van der Hoeft P, Yernault JC, Primo G: Combined heart and lung transplantation for Iymphangioleiomyomatosis. Lan cet 1:275, 1984
10 McCarty KS Jr, Mossier JA, McLelland R, Sieker MO: Pulmonary Iyrnphagioleiomyomatosis responsive to pro gesterone. N Engl J Med 303:1461-1465, 1980
11 Kamholz SL, Veith FJ, Mollenkopf FP, Pinsker KL, Kaleya RR, Norin AJ, Gleedman ML, Emeson EE, Merav AD, Brodman R, Fell SC, Sheldon M, Montefusco CM: Single lung transplantation with cyclosporin immu nosuppression. J THORAC CARDIOVASC SURa 86:537-542, 1983
8 7 6 Wellens et al.
12 Guz A, Noble MI, Widdicombe JG: The effect of bilateral block of vagus and glossopharyngeal nerves on the ventila tory response to CO 2 of conscious man. Resp Physiol 1:206-210, 1966
13 Reitz BA, Gaudiana VA, Hunt SA, Wallwork J, Billing ham ME, Oyer PE, Baumgarter WA, Jamieson SW, Stinson EB, Shumway NE: Diagnosis and treatment of
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allograft rejection in heart-lung recipients. J THoRAe CARDIOVASC SURG 85:354-361, 1983
14 Wohl MEB, Chernick V: State of the art. Bronchiolitis. Am Rev Respir Dis 118:759-780, 1978
15 Editorial: Obliterative bronchiolitis. Lancet 1:603-604, 1982
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