MONDAY AFTERNOON, MAY 7, 1990

1:30 p.m. SCIENTIFIC SESSION - Sheraton Ballroom

7. Heart and Lung Transplantation for Terminal Cystic Fibrosis. A Four Year Experience

MARC R. deLEVAL‡, JOHN WALLWORK*,

ROSALIND SMYTH", BRUCE WHITEHEAD",

MARTIN ELLIOTT* and TIMOTHY HIGENBOTTAM*

Cambridgeshire, United Kingdom

Sponsored by: Jaroslav Stark, London, United Kingdom

The management and outcome of 85 CF patients (pts) assessed for HLT are reviewed. 62 pts were accepted, 18 died while waiting for HLT and 27 aged 5-37 years (mean 19.3 years) had HLT. All had bacterial infection at the time of HLT. All donor organs were from distal procurement. Immunosup-pression was maintained with cyclosporin and azathioprine. Rejection episodes (RE) were treated with methylprednisolone. Daily monitoring of lung function (FEV1) was found to be a non-specific early indicator of infection or RE. Diagnosis was then established by transbronchial biopsy (TBB). There were 7 deaths (5 within 3 months of HLT). Causes of death were: early graft failure (1), aspiration pneumonia (1), Candida septicaemia (1), acute respiratory distress syndrome (1) and obliterative bronchiolitis (3). Actuarial probability of surviving to 1 year was 72%. Compared to other pts, CF pts (1) have no more RE (mean of 2 at 3 months and 0.3 per 3 months thereafter). (2) have no more infections. (3) require 5-10 times more cyclosporin. (4) have a greater instance of diabetes (9 pts). Contributory factors to successful HLT include: (1) careful recipient selection; (2) meticulous donor selection and management; (3) use of aprotinin to reduce intra-operative bleeding; (4) better understanding of peri-operative ventilatory mechanics; and (5) mandatory use of TBB to diagnose and treat RE and infections.

*By Invitation

‡24th Evarts A Graham Memorial Traveling Fellow

8. Comparison of Outcomes of Double and Single Lung Transplant for Obstructive Lung Disease

JANET R. MAURER*. G. ALEXANDER PATTERSON,

TREVOR J. WILLIAMS*, THOMAS R. TODD and

THE TORONTO LUNG TRANSPLANT GROUP

Toronto, Ontario, Canada

Until recently it was thought that single lung transplantation (SLT) was contraindicated in patients with end stage obstructive lung disease (OLD) and that OLD required double lung (DLT) or combined heart-lung transplantation. We have compared the early post operative results of SLT in 4 patients having OLD with results obtained in 9 patients with OLD previously treated by DLT. The four SLT's were all female, mean ages 44 ± 3.7. Diagnoses were alpha I antitrypsin deficiency emphysema 2, idiopathic emphysema 2. Six of nine DLT's were female; the mean age was 43 ± 6.7. Four patients had alpha I antitrypsin deficiency, 1 had bron-chiolitis obliterans, 4 had idiopathic emphysema. Two of 9 DLT's died perioperatively. There were no SLT deaths. Preoperative, early (3 mos.) and post operative vital capacity (VC), forced 1 sec. expiratory volume (FEV,) and Six Minute Walk (SMW) tests for operative survivors are summarized:

*% Predicted **metres/minute

All DLT's and SLT's had lormal postoperative ABG's on room air without exercise desaturation. SLT's achieve a smaller increment in VC and FEV, than DLT's, but improvement in SMW is comparable. Our early results suggest that SLT is associated with lower operative mortality and equivalent functional results in comparison to DLT for OLD.

*By Invitation

9. Right and Left Ventricular Performance Following Single and Double Lung Transplantation

G. ALEXANDER PATTERSON, TREVOR J. WILLIAMS*,

JANET R. MAURER*, PETER LIU*, RON CARRERE*

and THE TORONTO LUNG TRANSPLANT GROUP

Toronto, Ontario, Canada

Combined heart/lung transplantation has been employed in patients with pulmonary disease when right ventricular (RV) function was impaired. By decreasing RV afterload and increasing RV ejection fraction (RVEF) single (SLT) or double (DLT), would be effective. We assessed RVEF and LVEF before and after SLT and DLT. Eight SLT recipients (7 idiopathic pulmonary fibrosis, 1 Eisenmengers Syndrome 6M, 2F;48.8±5.2Y) and 10 DLT recipients (7 obstructive lung disease, 3 bronchiectasis; 5M, 5F; 41.8±7.4Y) were studied pre transplant, 3 months and 1-2 years post transplant. RVEF and LVEF was measured under equilibrium conditions at rest and exercise using radionuclide imaging. Statistical analysis was performed using the paired "t" test. The results (mean % ±S.D.) are summarized:

Improved resting RVEF was noted initially and 1-2 years post SLT (P<0.025). Initial improvement was observed in resting RVEF post DLT (P<0.05), however, this improvement is not sustained. Preoperative LVEF (57.0 ± 9.2) for SLT and (55.8 ± 13.6) for DLT did not change postoperatively. The improvement in RVEF following SLT is likely attributable to the excessive pulmonary vascular resistance in this patient group in comparison to the DLT group. Marked impairment of RV function can significantly improve by isolated lung transplantation.

*By Invitation

10. The Importance of Acquired Diffuse Bronchomalacia in Heart-Lung Transplant Recipients with Obliterative Bronchiolitis

RICHARD J. NOVICK*, DILDAR AHMAD*,

ALAN H. MENKIS*, KEN R. REID*,

PETER W. PFLUGFELDER*, WILLIAM J. KOSTUK*

and F.N. McKENZIE*

London, Ontario, Canada

Sponsored by: Tomas A. Salerno, Toronto, Ontario, Canada

A progressive decline in pulmonary function has been reported in heart-lung transplant (HLT) recipients exhibiting obliterative bronchiolitis (OB) on transbronchial or open lung biopsy. We have performed 14 HLTs, with 1 month, 1 year, and 2 year actuarial survivals of 93±7%, 85±11%, and 62±18%, respectively. Three early recipients died of OB, and 4 of the 9 patients currently being followed have OB. All recipients have undergone serial bronchoscopies using topical analgesia. Four OB patients have developed diffuse bronchomalacia (BM), readily seen on bronchoscopy. BM usually involved the entire tracheo-bronchial tree, below the level of the tracheal anastomosis. In all cases, the bronchial mucosa appeared less vascular than usual; in 1 patient who died two and a half years postoperatively, diffuse ischemia and destruction of bronchial cartilage was confirmed histologically. All patients had significant retention of bronchial secretions beyond the collapsing main bronchi at bronchoscopy. Transbronchial biopsies revealed marked concentric narrowing of pulmonary arterioles and severe bronchiolar scarring, but no evidence of acute lung rejection or opportunistic infection. All 4 patients had marked functional airflow obstruction, with an FEV1 of 26±2% predicted, FVC of 51±4% predicted and a peak expiratory flow rate of 44±8% predicted at the time of bronchoscopic diagnosis of BM.

We conclude that diffuse BM occurs frequently in HLT recipients who have OB. Both BM and OB may cause airflow obstruction after HLT, and their effects may be additive. Diffuse BM may be a result of long-standing bronchial ischemia or due to chronic rejection, and may play an important role clinically in the declining respiratory status of HLT recipients with OB.

2:45 p.m. BASIC SCIENCE LECTURE

"ADVANCES IN CANCER RESEARCH - BENCH TO BEDSIDE

Louis Siminovitch, Toronto, Ontario, Canada

3:30 p.m. INTERMISSION - VISIT EXHIBITS

4:00 p.m. SCIENTIFIC SESSION - Sheraton Ballroom

11. Effect of Hypothermic Cardiopulmonary Bypass and Total Circulatory Arrest on Cerebral Blood Flow and Metabolism in Neonates and Small Infants

WILLIAM J. GREELEY*, ROSS M. UNGERLEIDER*,

FRANK H. KERN*, TIMOTHY J. QUILL* and

JOSEPH G. REVES*

Durham, North Carolina

Sponsored by: David C. Sabiston, Jr., Durham,

North Carolina

Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO₂) were measured in 25 infants undergoing repair of congenital heart defects. Xenon¹³³ clearance (to measure CBF) and jugular venous bulb sampling methodology (to measure CMRO₂) were used to examine the effects of bypass and circulatory arrest on CBF and CMRO₂. Patients were grouped based on bypass conditions: 1) moderate hypothermic cardiopulmonary bypass (MHCPB) at 25-28°C and continuous flow, 2) deep hypothermic bypass (DHCPB) at 18-20°C with continuous flow and 3) deep hypothermic bypass with total circulatory arrest (DHCA). CBF and CMRO₂ measurements were made before bypass (A); during stable hypothermic bypass (B + C) or at similar sampling times immediately before and after DHCA; rewarmed on bypass (D); and after bypass (E). Measurements were made at similar hematocrit, PaCO₂, and pump flow rate during bypass.

RESULTS:

Mean values ± S.D.: CBF and CMRO2 = ml/100gm/min *p < 0.001 Stage B vs A; **p < 0.01 Stage E vs A.

DISCUSSION:

These data indicate that CBF and CMRO₂ are significantly reduced during hypothermic bypass, principally related to temperature reduction. During hypothermic bypass, regardless of temperature or whether continuous flow or DHCA is used, the ratio of supply (CBF) to demand (CMRO₂) favors flow, suggesting luxury perfusion of the brain. However, after rewarming from DHCA, CBF and CMRO₂ remain reduced, suggesting post-ischemic hypoperfusion and a metabolic disturbance in oxygen utilization. Because oxygen extraction by the brain (defined as CaO₂-CvO₂/CaO₂) was the same in all groups, the CBF changes after DHCA appear to be related to altered metabolism, where flow is coupled to reduced metabolism. These data could explain the known transient neurophysiologic changes associated with DHCA. Future studies will evaluate the relationship of the duration of DHCA as well as varying reperfusion techniques to these findings.

*By Invitation

12. Low Flow Hypothermia Cardiopulmonary Bypass Protects the Brain

JULIE A SWAIN*, THOMAS MCDONALD*,

PATRICK GRIFFIN*, ROBERT S. BALABAN*,

RICHARD E. CLARK and TONI CECKLER*

Bethesda, Maryland

Cerebral protection during surgical procedures requiring circulatory arrest or low flow remains the factor that most limits the time for the critical part of the operative procedure. In-vivo "P-nuclear magnetic resonance spec-troscopy (NMR) was used to assess the metabolic state of the brain by measuring the concentration of adenosine triphosphate (ATP) and the in-tracellular pH (pHj). The degree of cerebral protection during deep hypothermic cardiopulmonary bypass (CPB) at low flow rates was compared to that during circulatory arrest. Sheep were instrumented with a naso-pharyngeal temperature probe, an arterial pressure catheter, jugular vein and femoral arterial CPB cannulae, and a radiofrequency coil over the skull. The animals were placed in the bore of a 4.7T magnet and NMR spectra were continuously recorded. The animals were cooled on CPB to 15°C, at which time either circulatory arrest (CA)(n = 5) or flows of 5ml/kg/min (n = 6) or lOml/kg/min (n = 7) were instituted for 2 hours. CA or a flow of 5ml/kg/min both resulted in severe intracellular acidosis and depletion of ATP. A flow of lOml/kg/min nearly completely preserved ATP and pHi.

Conclusions: Deep hypothermia with CPB flows as low as 10ml/kg/min can maintain brain high energy phosphate concentrations and intracellular pH for 2 hours in sheep. Previous studies from our laboratory have shown that these NMR findings positively correlate with improved survival and preservation of neurological function.

*By Invitation

13. "Cold Cerebroplegia" A New Technique of Cerebral Protection During Surgery of the Transverse Aortic Arch

JEAN BACHET*. DANIEL GUILMET*,

BERTRAND GOUDOT*. JEAN LUC TERMIGNON*,

GILLES DREYFUS* and GIOVANNI TEODORI*

Suresnes, France

Sponsored by: Christian Cabrol, Paris, France

Profound Hypothermia (PH) associated with circulatory arrest (CA) is the commonest method of cerebral protection during surgery of the aortic arch. However, this technique allows a limited time to perform the aortic repair. It also often necessitates prolonged Cardio-pulmonary Bypass (CPB) to rewarm the patient. This may be the cause of coagulation disorders or infection.

Selective perfusion of the carotid arteries can also be used. But, when the perfusion is derived from the main arterial line, it requires that the aorta be cross-clamped and supresses the possibility of "bloodless, open" distal repair.

To avoid the disadvantages of both techniques, we have developed a new technique of cerebral protection: after a regular CPB has been instituted, the carotid arteries are cannulated and perfused with blood cooled at 6 to 10°C. through a separate heath exchanger, and the core temperature is maintained at moderate hypothermia (25 to 28°C. rectal). To perform the "open" distal aortic repair, the CPB is discontinued while the carotid perfusion alone is maintained (300 ml/minute). When the distal repair is completed, CPB is resumed and carotid perfusion is discontinued.

Between 1984 and September 1989, fifty-three patients (mean age: 55 years) were operated on with this method (44 elective operations, 9 emergency procedures). Mean duration of CPB was 121 mn; (65-248) and of CA: 22 mn (10-51). The Electro-encephalogram, routinely recorded, showed return of the cerebral activity after a mean of 12 min. and normal activity after a mean of 60 min. There was no intraoperative death. Hospital mortality rate was 13% (7/53). One death was related to neurologic disorders. All patients, but one, awakened normally within eight hours after surgery. Two patients (4.3%)experienced a transient neurologic trouble (lateral hemianopsia). There was no hemorrhagic complication (24 hours average bleeding: 840 ±540 ml.)

In our experience the technique of "Cold cerebroplegia" has demonstrated to provide excellent cerebral protection. It needs no prolonged CPB, and does not limit the time necessary to perform the aortic repair. It may be considered as a safe alternative to PH associated with CA.

*By Invitation

14. Arterial Switch for TGA and VSD, 106 Patients

CLAUDE PLANCHE*, ALAIN SERRAF*,

FRANCOIS LACOUR-GAYET*,

JACQUELINE BRUNIAUX*, DANIEL SIDI*

and JEAN KACHANER *

Le Plessis Robinson and Paris, France

Sponsored by: Aldo R. Castaneda, Boston, Massachusetts

One hundred and six patients, 90 with TGA and 16 with DORV and sub-pulmonary VSD, underwent an arterial switch associated to a patch closure of the VSD, from January 1983 to October 1989.

Aortic coarctation (CoA) was associated in 28 patients and subaortic obstruction in 9. Ten patients had multiple VSD. Malalignment of the conal septum was constant in the 16 patients with DORV and present in 15 additional patients with TGA. According to Yacoub's classification of coronary arteries, there were 72 type A, 21 type D; 12 type E and 1 type C. The great vessels were side by side in 15% of the patients. Age at operation ranged from 4 days to 4 years (mean = 2.8 months ± 5.2). Thirty-two infants were less than one month of age. Thirty-three patients underwent previous surgery including: 9 pulmonary artery (PA) banding alone, 12 PA banding and CoA repair and 12 CoA repair alone. Mean time between the first procedure and the switch was 2.2 months. Four patients with associated CoA underwent a one stage repair through sternotomy.

The VSD was first closed and approached through the RV in 50%, the RA in 40% and PA in 10%. The arterial switch was then performed according to the technique followed in our institution and the Lecompte maneuver was always done.

Early mortality was 15.1% (70 CL = 11.5% - 18.7%). Causes of death were either related to coronary artery kinking (8 patients) or to anatomy and size discrepancy of great vessels (8 patients). Univariate analysis could not find any significant risk factor of early mortality.

Mean follow up of 24 months ± 21.5 was achieved in all but 2 survivors. There was one late death. Eleven patients (12.2%) underwent successful reoperation for: 7 pulmonary stenosis, 2 residual VSD, 2 recurrent coarctation and 1 SVC stenosis.

Actuarial survival and freedom from reoperation at 4 years were respectively 82.7% and 85.6%.

In conclusion, arterial switch in complex TGA is a safe procedure which provides satisfactory early and mid-term results.

*By Invitation