WEDNESDAY MORNING, MAY 8, 1991

7:30 a.m. FORUM SESSION II - General Thoracic Surgery

International Ballroom

F11. Platelet Activating Factor Antagonist Enhances Lung Preservation in a Canine Model of Single Lung Allotransplantation

PHILIP C. CORCORAN*, YINING WANG*,

NEVIN M. KATZ, MARIE L. FOEGH*,

ALI R. ANALOUEI* and ROBERT B. WALLACE

Silver Spring, Maryland and Washington, D. C.

Optimal techniques for lung preservation have yet to be defined. Platelet Activating Factor is a phospholipid released by a variety of cells which promotes inflammation and produces pulmonary abnormalities similar to post-transplantation pulmonary dysfunction. We investigated the effect of the Platelet Activating Factor Antagonist BN 52021 (P) as compared to that of Desferroxamine (D), a commonly available iron chelator known to improve lung preservation. Differential lung function and pulmonary hemodynamics were used to assess preservation after a six hour period of cold ischemic storage in a canine model of left lung allotransplantation. Thirty size- and weight-matched mongrel male canines were used for 15 transplant procedures randomized to one of three preservation techniques. The University of Wisconsin (UW) Solution was used as the basic flush solution. P was added to the flush solution in one group (10 mg/kg-N = 5), D was added to the flush solution in a second group (10 mg/kg-N = 5). No additives were used for the control animals (N = 5). P and D were administered to respective donor animals 30 min prior to organ harvest (10 mg/kg) and recipient animals 30 min prior to reperfusion (10 mg/kg). The pulmonary artery flush solution was administered at 40 ml/kg over 4 min. Recipient animals were monitored with balloon-tipped, flow-directed catheters in both pulmonary arteries and ultrasonic flow probes around each pulmonary artery. Solid state micromanometers measured pressures in the pulmonary artery, the left atrium and the left ventricle. Systemic arterial (SA), right and left pulmonary venous (RPV and LPV) and mixed venous blood samples were analyzed at 1, 2, 4 and 6 hours post-transplantation. Transplanted lung pulmonary venous oxygen tension (P_VO2, alveolar-arterial gradient (A-aGRAD), in-trapulmonary shunt fraction (Qs/Qt). pulmonary vascular resistance (PVR), dynamic pulmonary compliance (DPC) and systemic vascular resistance (SVR) at six hours post-transplantation are reported below as mean ± standard error.

		PVO2 (mmHg)				A-aGRAD (mmHg)
	UW	UW+P	UW+D		UW	UW+P	UW+D
LPV	202±81	282±53*	307±96*	LPV	468±80	271±69*	252±88†
		QSQT RATIO (%)				PVR (Dyneseccm-5)
	UW	UW+P	UW+D		UW	UW+P	UW+D
LPV	0.54±0.19	0.21±0.04*	0.16±0.05*	LL	319±54	149±71*	115±62*
		DPC (ml/cm H2O				SVR(Dyneseccm-5)
	UW	UW+P	UW+D		UW	UW+P	UW+D
LL	32±6	52±6†	50±3†	SC	1146±171	1090±95*	1063±440*
(*P<0.05,†P<0.01,*P = No Significance as compared to control, LL = left lung, SC = systemic circulation)

Proton Magnetic Resonance bpectroscopy was performed on specimens from recipient animals to determine total extravascular lung water content (TEVLW). PhadaTEVLWof 57.3 ± 6.4% as compared to 51.9 ± 7.7% for D (P = NS) and 88.6 ± 9.2% for controls (P<0.05). We conclude from these data that the Platelet Activating Factor Antagonist BN 52021 enhances lung preservation to a similar degree as Desferroxamine in a model of canine single lung allotransplantation.

*By Invitation

F12. Future Horizons of Lung Preservation by Application of PAF-Antagonists Compared to Current Clinical Standard (Euro-Collins Flush-Perfusion Versus Donor Core Cooling by Extracorporeal Circulation)

THORSTEN WAHLERS*, STEFAN HIRT*,

HANS-GERD FIEGUTH*, MICHAEL JURMANN*,

AXEL HAVERICH* and HANS GEORG BORST

Hannover, Germany

With the introduction of platelet activating factor antagonists (PAFa) a direct inhibition of ischemia induced reperfusion injury can be achieved by prevention of platelet activation, reduction of microvascular leakage and PAF-induced bronchoconstriction.

Meanwhile two preservation methods are established for clinical lung preservation: donor core cooling by extracorporeal circulation (DCC) and pulmonary artery flush using prostracyclin and Euro-Collins solution (P/ECS). In order to improve results obtained with both methods, we compared the application of a PAF-antagonist (WEB 2170 BS) (0.3 mg/kg bodyweight [bw]/h) for the donor, perfusion solution and throughout the first 6 hours of reperfusion in combination with prostacyclin (20 ng/kg bw/min) and Euro-Collins solution (60cc/kg bw) (P/ECS/PAFa).

Eighteen canine heterotopic heart, orthotopic left lung transplants (tx) were performed in 3 groups of six dogs each after 6 hours of cold ischemia (group A: DCC, group B: P/ECS, group C: P/ECS/PAFa). Myocardial preservation was achieved using St. Thomas Hospital solution (20cc/kg bw) in all groups. After tx cardiorespiratory function was assessed at FiO2 of 0.4.

Results: Post tx superior results were observed with P/ECS/PAFa as expressed by significantly improved oxygenation (PO2) (tab), while cardiac output and pulmonary artery pressure only showed insignificant changes.

tab.: arterial PO2 (mmHg) (mean values + standard deviation)

hours post tx:	3	6	9	12
Group A (DCC):	82.6 + -41.7	76.7 + -41.1	73.6 + -40.4	50.8 + -27.1
Group B (P/ECS):	179 + -70.2	162.3 + -61.4	118.6 + -38.8	122.8 + -34.4
Group C (P/ECS/PAFa):	273.0 + -26.4**/*	238.8 + -63.1**/*	236.0 + -27.0**/*	22.5 + -41.7**/*
p-values (C vs A/C vs B): *p<0.05, **p<0.01

It is concluded, that using the PAF-antagonistic activity of WEB 2170 BS in lung preservation compared to current clinical standards, superior results can be obtained as demonstrated by significantly improved oxygenation following 6 hours of cold ischemia in a canine transplant model.

*By Invitation

F13. Experimental Study on Ischemia-reperfusion Lung Injury in Cardiopulmonary Bypass Using a Rabbit Model

HIKARU MATSUDA *, TOHUR KURATANI*,

YOSHIKI SA WA *, MITSUNORIKANEKO*, SUSUMU

NAKANO* and YASUNARUKAWASHIMA

Osaka, Japan

Pulmonary dysfunction after cardiopulmonary bypass (CPB) may relate to possible ischemia-reperfusion lung injury from secession of pulmonary artery (PA) blood flow. Adults white rabbits (n = 33) were subjected to partial CPB (80 ml/min/kg) under median sternotomy at 32 C with homologous blood prime. Unilateral PA was occluded (PAO+) simulating total CPB using the other as control (PAO-). After 2 hours, CPB was terminated with separate perfusion for PAO+ lung (reperfusion:REP, 60 min) by either of whole blood, leukocyte-depletion (LD by filter), or inhibition of complement activation by FUT (nafamstat mesilate). Lungs were deflated in these groups, and inflated by oxygen in the 4th group (OX). Pulmonary tissue ATP, tissue blood flow (TBF), trans-pulmonary gradients of leukocytes count and C5a level(d-LK, d-C5a), and AaDo₂ were measured.

In the control group, PAO + lung showed significant decreases in ATP and TBF at the end of CPB with subsequent significant changes in all indices at REP compared to pre-value. The LD and FUT groups showed significant preventions in these changes and OX-group in part.

	Control				LD	FUT	OX
	PAO -		PAO +
	CPB	REP	CPB	REP	REP	REP	REP
ATP (% to pre)	99	98#	*52	*80	920	97#	98#
TBF (% to pre)	*48	96#	*16	*58	92#	94#	64
d-LK (/mm!)	-	74#	-	*611	51#	52#	*432
d-C5a (ng/ml)	-	4#	-	*25	9#	2#	*23
AaDo2 (mmHg)	-	154#	-	*406	154#	162#	159#
(CPB & REP: at each end, C5a:at 15 min. *: significant to pre, #: significant to PAO +, mean value are presented)

These results indicate that complete secession of PA flow during CPB may have a risk to cause ischemia-reperfusion lung injuries with involvements of leukocyte and complement activations.

*By Invitation

F14. Evaluation of Lung Metabolism During Successful 24-hour Canine Lung Preservation

HIROSHI DATE*, AKIHIDE MA TSUMURA*,

JILL K. MANCHESTER*, HIDEFUMI OBO*,

ORIANE LIMA*, JOSHUA M. COOPER*, SUDHIR SUNDARESAN*

and OLIVER H. LOWRY*

St. Louis, Missouri

Using a canine left lung allotransplantation model, we evaluated 24-hour lung preservation using two electrolyte preservation solutions, LPD (low potassium dextran) and LPDG (LPD solution plus 1% glucose). Both donor lungs were flushed with either LPD (group I, n = 6) or LPDG (group II, n = 6), inflated with 100% oxygen and preserved for 24 hours at 10 degrees C. The left lungs were implanted using a pulmonary cooling jacket to prevent re-warming of the lung graft and omentopexy was performed around the bronchial anastomosis. An inflatable cuff with a subcutaneously placed injection port, was placed around the right pulmonary artery at the time of the transplant. Biopsies of the right lung were performed at intervals during preservation for metabolic studies, which included ATP, PCr, glucose, G-6-P, lactate, citrate and malate measured via enzyme assay. Function of the transplanted lung was assessed by measurement of arterial blood gases during temporary occlusion of the contralateral pulmonary artery. Immediately after transplant the PaO2 (FiO2 = 1.0) during right pulmonary artery occlusion was significantly greater in group II than group I (518 ± 50 versus 376 ± 56 mmHg; p<0.05). Surviving animals were restudied at intervals up to 22 days at which time they were sacrificed.

In group I, 3 animals survived for 22 days with good lung function while the other 3 were sacrificed after 1, 2 and 10 days because of lung edema, pneumonia and rejection respectively. In group II, 4 animals survived until elective sacrifice while 2 others were sacrificed on day 8 and day 22 because of LA thrombus and rejection respectively. PaO2 during right pulmonary artery occlusion in group II was 546 ± 20 mmHg at 3 days (n = 6), 468 ± 45 mmHg at 8 days (n = 5), and 426 ± 30 mmHg at 22 days (n = 4) which were not significantly different from results in group I. Metabolic studies of the right lung at the end of 24 hours preservation revealed the following results:

	ATP	PCr	Glucose	G-6-P	lactate	citrate	malate
Group I	1.15±0.10	0.28±0.03	02±0.0	11.7±3.6	0.19±0.03	33.1±9.0	15.7±4.5
Group II	1.23±0.09	0.34±0.04	23.5±2.7	82.4±17.2	1.58±0.35	170.8±23.9	58.2±10.0
p Value	NS	NS	<.001	<.01	<.01	<.001	<.01
(Concentrations are u mole/g wet weight for ATP, PCr, glucose and lactate, and n mole/g wet weight for G-6-P citrate and malate).

We conclude that lung preservation at 10 degrees C is associated with maintenance of aerobic cell metabolism and that the addition of glucose to the preservation solution improves lung preservation. Both glycolysis and the citric acid cycle are maintained during such preservation as an energy source, thus protecting lung cells.

*By Invitation

F15. Unilateral Donor Lung Dysfunction Does Not Preclude Successful Contralateral Single Lung Transplantation

JOHN D. PUSKAS*, TIMOTHY L. WINTON*,

JOHN MILLER*, MASINA SCAVUZZO* and

G. ALEXANDER PATTERSON

Toronto, Ontario, Canada

Application of single lung transplantation remains limited by a severe shortage of suitable donor lungs. Potential lung donors are often deemed unsuitable because accepted criteria for lung donors (clear CXR bilaterally; PaO2>300 mmHg with FiO2 = 1.0, PEEP = 5 cm H2O; absence of purulent secretions) may not distinguish between unilateral and bilateral pulmonary pathology. Many adequate single lung grafts may be discarded as a result of contralateral aspiration or pulmonary trauma. We have recently employed intraoperative unilateral ventilation and perfusion to assess single lung function in potential donors with contralateral lung pathology. In the 11-month period ending October 1, 1990, we performed 18 single lung transplants. In 4 of these cases (22%), donor CXR and/or bronchoscopy demonstrated significant unilateral lung injury. Donor PaO2 (FiO2 1.0; PEEP 5 cm H2O) was below the accepted level in each case (246 ± 47 mmHg, mean ± STD). Through the sternotomy employed for multiple organ harvest, the pulmonary artery to the injured lung was clamped. A double-lumen endotracheal tube or endobronchial balloon occlusion catheter was used to permit ventilation of the uninjured lung alone. Repeat PaO2 (FiO2 1.0; PEEP 5 cm H2O) revealed excellent unilateral lung function in all 4 cases (499.5 ± 43 mmHg; p<0.0004). These single lung grafts (3 right, 1 left) were transplanted uneventfully into 4 recipients (3 pulmonary fibrosis, 1 primary pulmonary hypertension). Early post-transplant lung function was adequate in all patients. Two patients were extubated within 24 hours. There was 1 late death due to rejection and aspergillus infection; the other 3 patients are alive and doing well. We conclude that assessment of unilateral lung function in potential lung donors is indicated in selected cases, may be quickly and easily performed and may significantly increase the availability of single lung grafts.

*By Invitation

F16. Short and Long Term Results of Experimental Wrapping Techniques for Bronchial Anastomosis

JOSEPH LOCICERO, III*, MALEK MASSAD*,

JUNICHI OBA*, MICHAEL BRESTICKER*

and RODNEY GREENE*

Chicago, Illinois

Sponsored by: Robert W. Anderson, Chicago, Illinois

Major complications of bronchial anastomoses for either transplantation or sleeve resection include early leak, fistula formation, granulation tissue and stenosis. To evaluate the impact of technique on these complications we designed a non-immunocompromised canine model with a totally ischemic bronchial segment. We wished to discover the incidence of early and late complications of a telescoping anastomosis and if wrapping techniques modify them. We autotransplanted 2.5 cm of left mainstem bronchus by telescoping 1mm of proximal into distal bronchus sutured with interrupted 4-0 polyglactin. The animals were divided into four groups: no wrap (I); omental pedicle wrap (II); detached free omental wrap (III); and gelfoam soaked porcine omental extract (Angiomedical Corp., New York) (IV). Weekly bronchoscopy assessed airway stenosis. Following euthansia at 70 days, the luminal areas of the proximal and distal anastomoses were compared to the origin of the main bronchus.

RESULTS
	Control (I)	Pedicle (II)	Free (III)	Extract (IV)
Visible Stenosis	3/10	2/10	3/10	1/10
Proximal Ratio (%)	70 +/-13	82 +/-16	68 +/-14	88 +/-10
Distal Ratio (%)	73 +/-13	80 +/-12	64 +/-13	88 +/-10

No airleak or infection occurred in any group at any time. We conclude that wrapping of a telescoped anastomosis is not necessary to prevent early complications. However, no method completely eliminates stenosis development. Further experiments are required to determine the effects of immunomodulation on this model.

*By Invitation

F17. Oncogene Activation in Esophageal Cancer

ALAN G. CASSON*. TAPAS MUKHOPADHYAY*,

KAREN R. CLEARY*, JAE Y. RO*, SUSAN R. CAFFERTY*

and JACK A. ROTH

Houston, Texas

The molecular genetic events that contribute to the development of esophageal cancer are unknown. The aim of these studies was to screen esophageal tumors for mutations in selected oncogenes. DNA was recovered from 24 archival pathology specimens (10 squamous and 14 adenocarcinoma, with normal esophagus from the resection margin) and target oncogene sequences of interest were amplified in vitro using the polymerase chain reaction (PCR). To screen for mutations in the p53 oncogene, the technique of single stranded conformational polymorphism analysis (SSCP) was developed where PCR-amplified DNA was labelled with radioisotope. Paired samples (tumor and corresponding normal tissue) were then elec-trophoresed across non-denaturing polyacrylamide gels. Relative differences in electrophoretic mobility between radiolabelled samples were found to occur with mutations in the DNA sequence studied, and have now been detected in 5 of the 24 tumor samples (20%). One adenocarcinoma has been sequenced, and a mutation (CAT, histidine) confirmed at codon 273 (normal: CGT, arginine). No mutation was detected in Barrett's epithelium (with low grade-dysplasia) adjacent to this tumor.

In summary, this is the first report of a mutated oncogene in esophageal cancer, implicating p53 in tumorigenesis. Such molecular events may well have clinical prognostic significance for patients with Barrett's epithelium and high-grade dysplasias, as an early marker of tumor development.

*By Invitation

F18. Laser Sealing of hand Sewn Esophageal Anastomoses

JOSEPH S. A UTERI*, MEHMET C. OZ*,

JUAN A. SANCHEZ*, VALLUVAN JEEVANANDAM*,

MICHAEL R. TREAT* and CRAIG R. SMITH*

New York, New York

Sponsored by: Keith Reemtsma, New York, New York

Dehiscence rates of 5-20% have been reported for esophageal anastomoses. Causative factors include ischemia, tension, foreign body reaction, microabscesses, and negative pressure within the thoracic cavity. Because laser assisted tissue sealing (LATS) has been shown to improve anastomotic strength in other tissues, the efficacy of LATS was assessed in a canine model of intrathoracic single-layer hand-sewn esophageal anastomosis. Paired 2 cm transverse incisions (one laser sealed, one control) were made in the proximal and distal esophagus in eight dogs. Both were closed with interrupted single layer 4-0 polyglycolic acid sutures. One closure in each pair was selected at random for LATS, beginning with application of sealant solution (SS), followed by 3 minutes of exposure to diode laser energy (wavelength 808 nm, power density 9.6 W/cm²). SS combines albumin (0.2 cc) and sodium hyaluronate (0.4 cc), used to provide a protein matrix across the anastomosis for ingrowth of fibroblasts, with indocyanine green (1 gtt), which increases uptake of laser energy by the targeted tissues because of selective absorption at a wavelength (805 nm) matching that of the diode laser. Each esophagus was removed and infused with saline under pressure, either at the time of sealing or 7 days postoperatively. Bursting pressures, defined as the intraluminal pressures at which saline leakage appears, are summarized below:

Time	Control	Laser Sealed
0 days	79 ± 58 mmHg	204 ± 98 mmHg	p<.05
7 days	166 ± 87 mmHg	259 ± 38 mmHg	p = ns

HPS staining of laser sealed anastomoses revealed minimal thermal injury to the mucosal surface initially, with regeneration of intact mucosal lining by 7 days postoperatively. Foreign body reaction to SS was not seen. LATS is a rapid, simple technique which increases the strength of single layer hand sewn esophageal anastomoses, and may decrease the incidence of anastomotic leakage in clinical practice.

*By Invitation

F19. Immunotherapy Alters Lung Cancer Response to Oxidative Stress

HELEN W. POGREBNIAK*, WILBERT D. MATTHEWS*

and HARVEY I. PASS*

Bethesda, Maryland

Sponsored by: Robert B. Wallace, Washington, D.C.

Selected immunotherapy (tumor necrosis factor [TNF]) and chemotherapies generate reactive oxygen species (ROS). It is unknown whether lung cancer (A549) sensitivity to ROS therapy is altered by TNF, i.e. are cells made "resistant" via increased oxidative buffering through TNF-induction of manganese superoxide dismutase (MnSOD). To answer this question, we examined A549 cytotoxicity after exposure to hypoxanthine (H)/xanthine oxidase (XO) with/without TNF pretreatment, and documented changes in MnSOD due to the TNF pretreatment. METHODS: A549 cells, treated with 0, 0.1, 1.0, or 10 ug/ml TNF for 24 hours (n = 13 experiments), were then exposed to 1 mM H/0.1 u/ml XO for 7.5-60 minutes. Controls received H, XO, or media alone. All cells were then washed, and incubated for 5 days, at which time viability was quantitated as the surviving fraction (SF^o) of cells compared to controls using the tetrazolium reduction assay. TNF exposed/unexposed cells were examined for MnSOD and actin using p³² labelled cDNA probes, with calculationn of the expression index (E.I.)- RESULTS: HXO caused a time-dependent decrease in survival; however, pretreatment with TNF at any dose increased cell survival significantly. TNF-exposed cells also increased their expression of MnSOD.

MnSOD E.I.	[TNF]	7.5 min	15 min	30 min	45 min	60 min
1.00	0	SF:74±3	53 ± 3°	31 ± 2°	23 ± 1°	15 ± 1°
4.49	0.1	SF:81±3	65 ± 3*°	39 ± 2*°	27 ± 1*°	19 ± 2*°
4.81	1.0	SF:83±2*	66 ± 3*°	39 ± 2*°	27 ± 1*°	19 ± 2*°
5.54	10.0	SF:84±3*	69 ± 3*°	38 ± 2*°	28 ± 1*°	18 ± 1*°
*p2<0.05 from 0 ug/ml TNF; op2<0.05 from 7.5 minutes

CONCLUSIONS: TNF pretreatment, even at small doses, may confer resistance of lung cancer cells to subsequent ROS-based therapies. The resistance of these clones may be due to increased expression of MnSOD. It is possible that alterations in lung cancer cell oxidatitive buffering capacity by immunotherapy based regimens could lead to subsequent treatment failure, especially if the TNF is given concurrently with the other therapies.

*By Invitation

F20. Expanded Applications of Diagnostic and Operative Thoracoscopies

AKIO WAKABAYASHI Orange, California

Thoracoscopy was originally developed 80 years ago but has been underutilized in recent years. Over the past 20 years, the author performed thoracoscopy with increased frequency; 150 cases from 1971 to 1986 (9.4/year) vs. 146 cases from 1987 to 1990 (36.5/year). This increase was due to its expanded applications using the improved optic/video systems and carbon dioxide (CO₂) or neodymium yttrium aluminum garnet (YAG) lasers. Diagnostic thoracoscopies included; 59 cases without biopsy and 144 cases with biopsies (pleura 99, mediastinal and aortopulmonary window lymph nodes 25, lungs 15, or others 5). Operative thoracoscopies that were rarely performed before have been carried out more frequently than diagnostic thoracoscopies since 1987 (88 vs. 58 cases). The applications of the operative thoracoscopy included: (1) debridgement of empyema 19, (2) YAG laser vaporization of malignant pleural implants in the treatment of recurrent massive pleural effusion in 3, (3) electrocautery or CO₂ laser treatment of spontaneous pneumothorax in 39, (4) CO₂ laser contraction of bullae in the treatment of diffuse bullous emphysema in 28; and (5) others 4. The operative mortality rate was low, 0.7% (2/296), the morbidity minimal, and postoperative recovery periods were markedly shorter than those after thoracotomy. The diagnostic thoracoscopy prevented many unnecessary exploratory thoracotomies and achieved very high diagnostic accuracy of 99% (201/203). The operative thoracoscopy replaced thoracotomy in many areas and has opened a new horizon in the management of previously untouched areas.

*By Invitation

WEDNESDAY MORNING, May 8, 1991

9:00 a.m. SCIENTIFIC SESSIONS - International Ballroom

38. Operative Treatment of Ebstein's Anomaly

GORDONK. DANIELSON, DAVID J. DRISCOLL*,

DOUGLAS D. MAIR*, CAROLE A. WARNES* and

WILLIAM C. OLIVER, JR. *

Rochester, Minnesota

Between 1972 and June 1990, 179 patients with Ebstein's anomaly have undergone repair. Ages ranged from 11 months to 64 years. In 72%, tricuspid valve reconstruction was possible and in 26% a prosthetic valve, usually a bioprosthesis, was inserted. Two percent underwent plication and a modified Fontan procedure. There were 12 hospital deaths (6.7%). All 21 patients who had an accessory conduction pathway (Wolff-Parkinson-White syndrome) underwent successful division of the pathway as part of their operative treatment. Follow-up of patients for more than two postoperative years shows 92% to be in New York Heart Association Class I or II. There were 6 late deaths, most sudden and presumably secondary to cardiac arrhythmia. Only 2 patients (1.7%) required reoperation following valve reconstruction (1 and 7 years later, respectively). Exercise testing in patients preoperatively and again late postoperatively snowed a significant improvement in performance; maximal oxygen consumption increased from a mean of 50% of predicted value before operation to a mean of 80% of predicted value after surgery. Postoperative echo-Doppler assessment in patients having valve reconstruction has shown excellent tricuspid valve function in most patients.

*By Invitation

39. Ventricular Septal Defect with Tricuspid Pouch with and without Transposition: Anatomic and Surgical Considerations

FAROUK S. IDRISS, ALEXANDER J. MUSTER*,

MILTON H. PAUL*, CARL L. BACKER* and

CONSTANTINE MAVROUDIS

Chicago, Illinois

Tricuspid valve pouch (TVP) covering a ventricular septal defect (VSD), which decreases its effective orifice, and the left to right shunt, may be misleading the surgeon. Conversely, in transposition of the great arteries (TGA), the bulging TVP may result in left ventricular outflow tract (LVOT) obstruction. In a 10 year review, operated patients were divided into two groups since the effect of the TVP is influenced by which ventricle has the higher pressure. Group I: VSD without TGA and Group II: VSD with TGA. Group I: In 72 of 392 patients, tricuspid valve leaflet (TV) was incised to expose the edges of the true VSD in order to accomplish proper repair. Of those, there were 48 with TVP. The diagnosis of TVP was established by angiography, echocardiography or at surgery. Ages at operation ranged from 5 months to 22 years and the Qp/Qs from 1 to 2.8. 16 had shunts less than 1.5. In one, the TVP produced 40 mm/Hg gradient in the right ventricular outflow tract. At surgery, through a transatrial approach the pouch was opened radially and the actual VSD patched and the TV repaired. There was no mortality, no significant complications, or TV dysfunction. The average postoperative hospital stay was 4 days. Group II: 6 patients out of 83 operated for TGA with VSD had significant LVOT obstruction from TVP. 5 of those had a Mustard procedure, 2 requiring a LV to PA conduit and in 2 of the 5 the VSD was closed through the PA. One patient had heart transplant following atrial repair and TV replacement. The sixth patient in Group II had a successful arterial switch at 9 years of age and after the presence of LVOT obstruction was proven to be due to TVP.

We conclude that presence of TVP in Group I may mislead to closing false small openings produced by TVP rather than the actual VSD. Incising the TVP is safe and essential for proper exposure and closure of the defect. We recommend surgical repair of anatomically large VSD occluded by TVP even though the left to right shunt may be small. TVP should not be confused with the rare aneurysm of the membranous septum. In Group II, the systemic RV pressure can push the TVP into the LVOT causing significant obstruction and may also be responsible for TV insufficiency following atrial baffle repair. Arterial switch is preferred since it places the obstructive tricuspid tissue in the lower pressure ventricle.

*By Invitation

40. Intermediate-term Survival and Functional Results After Arterial Repair for Transposition of the Great Arteries

FLAVIAN M. LUPINETTI*, EDWARD L. BOVE,

A. REBECCA SINDER*, LOUISE B. CALLOW*,

JOH N. MELIONES*, DENNIS C. CROWLEY*.

ROBERTH. BEEKMAN*, L. LUANN MINICK*

and AMNON ROSENTHAL*

Ann Arbor, Michigan

An assessment of late morbidity and mortality is essential before arterial repair can be considered truly corrective for patients with transposition of the great arteries (TGA). We report our experience with 112 patients who underwent arterial repair in order to evaluate early and intermediate-term results. Operation was performed at a median age of 6 days with 73 patients operated on within the first 14 days of life. Coronary artery anatomy was abnormal in 27 patients. Simultaneous procedures were ventricular septal defect closure (n = 33) and repair of interrupted aortic arch (n =2) or coarctation (n = 5). Hospital mortality was 7/112 (6%), with 3 deaths in the most recent 90 patients (3%). There was one late, noncardiac death. Reoperation for pulmonary artery (PA) stenosis was required in 9 of the first 63 patients (14%), all of whom underwent PA reconstruction with separate patches for closure of the coronary excision sites. Of the last 49 patients, all of whom had PA reconstruction with a single pantaloon pericardial patch, 1 (2%) required reoperation for PA stenosis. No other patients have undergone reoperation. Doppler/echocardiograms performed in 102 of 105 surviving patients at a mean of 13 months after repair have demonstrated normal left ventricular function, an absence of left ventricular outflow gradients, and no more than trivial aortic regurgitation. Gradients across the PA were 19 ± 3 mm Hg in patients with separate PA patches and 7 ± 3 mm Hg in those with a single pantaloon patch (p = 0.011). Follow-up is 96%) complete from 1 month to 8 years after operation (mean 2.5 years). Actuarial survival at 5 years including operative mortality was 93%. All patients are in sinus rhythm and none requires antiarrhythmic medications. These data suggest that PA reconstruction with a single pantaloon patch may be associated with a decreased requirement for reoperation. Intermediate-term survival and functional results are excellent following aterial repair for TGA.

*By Invitation

41. Factors Associated with Marked Reduction in Mortality for Fontan Operations in Patients with Single Ventricle

JOHN E. MAYER, JR., NANCYD. BRIDGES*,

RICHARD A. JONAS, FRANK L. HANLEY*,

JAMES E. LOCK* and ALDO R. CASTANEDA

Boston, Massachusetts

Fontan operations (FO) have historically carried higher operative mortality for patients with single ventricle (SV) than for those with tricuspid atresia. Between 7/88 and 6/90, 87 of 90 patients (96.7%) with SV survived FO (Group A) in one institution, while in the immediately preceeding two years (Group B), only 58 of 72 (80.6%) survived FO for SV (X² = 9.5, p<.01). Comparisons of preoperative factors in groups A and B showed no differences (all with p>. 10) in mean age (A = 6.1 +/- 5.2, B = 7.3 +/- 6.1 yrs), mean pulmonary artery (PA) pressure (A = 12.7 +/- 3.4, B = 12.3 +/- 3.8 mmHg), indexed pulmonary arteriolar resistance (A = 1.6 +/- .8, B = 1.14 +/- .6U), or fractions of patients with systemic or pulmonary venous anomalies (A =17/90, B = 19/72), with PA distortion (A = 13/90, B= 16/72), with age <4 yrs (A = 38/90, B = 26/72), with PA pressure >15 mmHg (A =15/90, B = 10/72, or with pulmonary arteriolar resistance >2 U (A =12/90, B = 4/72). Striking survival differences existed for subgroups with left AV valve atresia/stenosis (A =18/18, B = 14/21, p<.01) and PA distortion (A= 12/13, B = 8/16, p<.01). Differences in surgical management between the two groups included 1) use of cavo-pulmonary connections (A = 84/90, B = 45/72, p< .01), 2) minimizing the size of the intra-atrial baffle (A = 72/90, B = 16/72, p<.01). 3) prior bidirbidirec-tional Glenn for interim palliation (A = 10/90, B = 0/72, p<.01), and 4) fenestration of the intra-atrial baffle (A = 39/90, B =0/72, p<.01). We conclude that with these management modifications FO can now be carried out for patients with complex forms of SV with low mortality risk.

10:20 a.m. INTERMISSION - VISIT EXHIBITS

*By Invitation

11:05 SCIENTIFIC SESSIONS

42. Pulmonary Artery Sling: Results of Surgical Repair in Infancy

CARL L. BACKER*, FAROUK S. IDRISS, LAUREN D. HOLINGER*

and CONSTANTINE MAVROUDIS

Chicago, Illinois

Pulmonary artery (PA) sling is a rare congenital vascular anomaly in which the left PA originates from the right PA and encircles the right bronchus and trachea before entering the left hilum, passing between the trachea and esophagus. This causes severe compression of the trachea and right mainstem bronchus and most infants with this anomaly present with severe respiratory distress within the first year of life. Previous reviews of infants treated surgically for PA sling have reported high mortality with poor patency of the left PA in survivors.

Between 1953 and 1990, eleven children underwent surgical intervention for PA sling, nine males and two females. Age ranged from 8 days to 9 months (mean age 5 months). Bronchoscopy was performed in all patients and complete tracheal rings were the most common associated lesion (5 patients). Six patients had cardiac catheterization. Most recently, computed tomography and magnetic resonance imaging have been used to diagnose PA sling and associated complete tracheal rings when present. Surgical repair consisted of transection of the left PA at its origin from the right PA and reimplantation of the left PA into the main PA anterior to the trachea; via right thoracotomy (1), left thoracotomy (6), or median sternotomy (4). The last three patients in the series have had simultaneous pericardial patch tracheoplasty utilizing extracorporeal circulation at the time of pulmonary artery reimplantation.

There were no operative deaths. Two late deaths occurred, both from airway complications in infants who also had complete tracheal rings and tracheoplasty, at 7 months and 2.5 years postoperatively. Nine patients have had postoperative studies to determine the patency of the left pulmonary artery. Seven anastomoses are patent (78%).

PA sling can be repaired in infancy with low operative mortality and excellent long-term patency utilizing division and reimplantation of the left PA anterior to the trachea. We currently recommend repair at the time of diagnosis with median sternotomy and extracorporeal circulation with simultaneous pericardial patch tracheoplasty if complete tracheal rings are associated.

*By Invitation

43. Cardiac Preservation in Patients Undergoing Transplantation: A Clinical Trial Comparing University of Wisconsin Solution and Stanford Solution

DARRYL G. STEIN*, DAVIS C. DRINKWATER*,

HILLEL LAKS, LESTER C. PERMUT*,

SUSHEELA SANG WAN*, HOWARD I. CHAIT*,

JOHN S. CHILD* and SUNITA BHUTA *

Los Angeles, California

Recent laboratory investigations have shown significantly improved donor heart preservation and function when the University of Wisconsin solution (UW) is used for arrest and storage. These findings prompted us to compare UW to Stanford solution in a clinical trial. With the approval of our Investigational Review Board and notification of the FDA, patient enrollment began in February 1990. After obtaining informed consent, patients were blindly randomized to receive a heart arrested and stored in UW or a heart arrested in Stanford solution and stored in normal saline. Orthotopic transplants were performed in a routine manner. All hearts were initially reperfused with aspartate/glutamate enriched warm blood cardioplegia for 3 minutes followed by whole blood reperfusion. All patients received dopamine (5 ug/kg/min) and dobutamine (5 ug/kg/min) at the conclusion of cardiopulmonary bypass. Fourteen patients with a mean age of 50.9 were randomized to UW (Group 1), while fifteen patients with a mean age of 53.7 were randomized to Stanford (Group 2). Donor ages were similar with a mean age of 26.9 in group 1 and a mean age of 23.3 in group 2. Mean ischemic time in group 1 (150.7 minutes) was somewhat longer than in group 2 (131.3 minutes). Several differences were observed intraoperatively. The number of patients requiring defibrillation intraoperatively differed between groups with 14%(2/14) of patients in group 1 needing defibrillation compared to 53% (8/15) in group 2 (p<0.05, Fischer's Exact Test). The number of patients requiring temporary intraoperative pacing for junctional rhythm or heart block also showed a significant difference with 7% (1/14) of group 1 patients versus 47% (7/15) of group 2 patients requiring pacing (p<0.05). Intraoperative inotropic support in addition to our standardized protocol was required in 14% (2/14) of group 1 patients versus 40% (6/15) of group 2 patients. This reached near significance with a p value of 0.13. Ejection fractions as determined by transthoracic echocardiography on the first postoperative day were similar in both groups, 64 ± 3% (mean ± SEM) in group 1 and 65 ± 1% in group 2. With a follow-up of 1 week to 8.5 months, there were no early deaths (30 day) in either group and one late death in group 1. The death occurred in a patient who developed sepsis and multiorgan system failure 72 days after transplantation. We conclude: 1. UW is a safe and effective preservation solution for human cardiac transplantation. 2. Considering the decreased defibrillations, decreased intraoperative pacing, and decreased requirement for inotropic support in the UW group, UW appears to be superior to Stanford for donor heart preservation.

*By Invitation

44. University of Wisconsin Solution Versus Cystalloid Cardioplegia for Donor Heart Perservation: A Randomized Blinded Prospective Human Trial

VALLUVAN JEEVANANDAM*, MARK A. BARR*,

JUAN A. SANCHEZ*, JOSEPHS. AUTERI*,

CHARLES M. MARBOE*, FELICIA A. SCHANKEL*,

CRAIG R. SMITH* and ERIC A. ROSE

New York, New York

University of Wisconsin solution (UWS) improves and prolongs preservation of kidney, liver and pancreas grafts, but concerns about its viscosity and high potassium concentration have hindered its use in heart transplantation. After demonstrating the ability of UWS to prolong preservation times up to 18 hours with orthotopic baboon allografts and showing safety and efficacy in a pilot human trial, we started a randomized prospective trial to compare preservation, within a four hour donor ischemia limit, using UWS to crystalloid cardioplegia and saline storage (CCS).

Forty-two adult heart transplants performed between May and September 1990 were randomized into two groups: 1) UWS (n = 22) - donor hearts arrested (15 ml/kg, 80 mm/hg, 4C) and stored (4C) in UWS (n = 22), and 2) CCS (n = 20) - donor hearts arrested with crystalloid cardioplegia (15 ml/kg, 80 mm/hg, 4C) and stored in saline (4C). The recipient surgeon, data analyst, and pathologist were blinded to the randomization. Recipient age, gender, heart disease and preoperative inotropic support and donor age, gender, inotropic support, and mean ischemic time in hours (UWS 2'36" [1'36" to 2'53"], CCS 2'20" [2'20" to 2'44"] p = ns) were similar. Differences observed between the two groups included: 1) Mean time (minutes) to achieve stable sinus rhythm from reperfusion - UWS 5" (1' to 15'), CCS 19" (3" to 47") p<.02; 2) Intraoperative defibrillations - UWS 4/22, CCS 12/20 p<.02; 3) Transient cardiac pacing - UWS 2/22, CCS 10/20 p<.02; 4) Integrated postoperative enzyme (I/U) release over 48 hours - CPK: UWS 801.2 ± 468.7, CCS 1187 ± 717.7 p<.01, AST: UWS 207.6 ± 83.7, CCS 282.9 ± 69.0 p<.001. There was no difference in postoperative EKG, endomyocar-dial biopsy or hemodynamics (measured by mixed venous 02 sat and CO) at one week. One UWS patient died from sepsis.

UWS is safe for donor organ arrest and preservation despite high viscosity and potassium concentration. When compared to CCS, hearts preserved in UWS regained electrical activity quicker and had better myocardial protection as demonstrated by enzymatic analysis. Further investigation is required to determine the effects of UWS preservation on long term survival, incidence of rejection and graft atheroscerlosis, and to test the ability of UWS to extend donor ischemic time in human cardiac transplantation.

12:10 p.m. ADJOURN FOR LUNCH

*By Invitation