WEDNESDAY, April 8, 1987
6:45-8:30 a.m.
SIMULTANEOUS BREAKFAST SESSIONS**
(See Page 16)
C. ACUTE
MYOCARDIAL INFARCTION: CATH LAB, SURGERY OR NO INTERVENTION? - Columbus Hall
Moderator: Mortimer J. Buckley, M.D., Boston,
Massachusetts
D. TRANSPLANTATION:
PRACTICAL ASPECTS - Columbus Hall
Moderator: Edward B. Stinson, M.D., Stanford,
California
8:30 a.m. SCIENTIFIC SESSION - Grand Ballroom
32. The First Open Heart
Corrections of Ventricular Septal Defect: A 26 to 32 Year Follow-Up of 254
Patients
C. WALTON LILLEHEI, RICHARD L.
VARCO,
MORLEY COHEN, HERBERT E. WARDEN,
VINCENT L. GOTT, RICHARD A.
DEWALL,
CECELIA PATTON* and
JAMES H. MOLLER*
St. Paul and Minneapolis,
Minnesota; Winnipeg, Manitoba;
Morgantown, West Virginia;
Baltimore, Maryland; Dayton,
Ohio and St. Louis Missouri
Ventricular septal defects became a
correctable malformation on March 26, 1954. From that date thru I960, 254
patients (age 4 mo. to 21 yrs.) who underwent open repairs, and were
discharged, have been followed (97% complete) until death, or for 26 to 32 yrs.
(mean 23.2 yrs., 5408 pt. yrs.)
The purposes of this study were to determine:
survival, morbidity, hemodynamics, educational/employment attainments, and
relation of these to surgical technics.
Operations were done by cross
circulation (19 pts.), arterial reservoir (2 pts.), and bubble oxygenator (233
pts.). Forty-five patients were under 2 yrs. of age at operation. This group
had the first uses of patch VSD closure, ischemic arrest, and pacemakers
amongst other innovations. Forty-seven (late deaths) have occurred: 27 within 10
yrs., 9 between 10 and 20 yrs., and 11 beyond 20 yrs. The major causes of
deaths were: pulmonary vascular disease (9), reoperation (7); sudden and
unexpected (7), accidents (4), complete heart block (4), only 1 had a
pacemaker, and 4 died of congestive heart failure. Five other deaths were due
to a variety of single causes. There were 7 deaths from unknown causes. Late
complications were reoperations in (14); arrhythmias in (10), five of whom are
on treatment. Bacterial endocarditis has occurred in (3), all with closed
defects. Malignancies occurred in (4). Four have required pacemakers late. Only
10 of 245 pts. (4%) have any cardiac symptoms. Cardiac cath. was performed in
138 of 245 patients (56%), and many showed no change in pulmonary vascular
resistances (PVR). Serial studies showed a fall in PVR under 2 yrs. of age, and
an increase in some older patients. In 76%, there was no residual shunt. One
hundred thirty-five attended education beyond high school either technical or
college. Forty-seven obtained a bachelor's degree, and thirty-five attended
graduate school with 16 receiving a graduate degree. Amongst the latter, were 4
PhD's and 6 physicians (one of whom is a cardiac surgeon). The 200 long term
survivors have few significant medical problems, and have had excellent (above
average) educational attainments. Many of the late deaths/complications are now
preventable.
*By Invitation
**Admission will be by ticket only and will be limited.
Tickets must be obtained in the Registration Area of the Hyatt Regency Chicago
prior to 2:00 p.m. on Monday, April 6. There are no provisions for
pre-registration. Breakfast will be served until 7:00 a.m. only.
33. The Superiority of Continuous Cold Blood Cardioplegia in Achieving
Metabolic Protection of the Hypertrophied Human Heart
SHUKRI F. KHURI,
MIGUEL JOSA*
KENNETH G. WARNER*,
MICHAEL D. BUTLER*
and AMY HAYES*
West Roxbury, Massachusetts
Continuous measurements of
intramyocardial pH and hydrogen ion concentration ([H + ]) were obtained in 39
patients with left ventricular hypertrophy (LVH) undergoing valve replacement ±
CABG. Cardioplegia (CP) was administered through the aortic root (or the
orifice of the left main coronary) and the bypass grafts. Group I (15 patients)
received standard crystalloid K+ CP intermittently every 15 minutes.
Group II (15 patients) received blood K+ CP intermittently in a
similar fashion. Group III (9 patients) received the same blood CP but
continuously throughout the period of aortic clamping (AC). The groups were
computer-matched according to preop LV ejection fraction (EF) and LVEDP, AC
time, and integrated mean temperature (MT) during AC. In Table I below
(mean + SEM) there were no significant differences between the groups:
|
|
Group I
|
Group II
|
Group III
|
P (by AOV)
|
|
EF (<%)
|
49 ± 2.9
|
43 ± 3.6
|
55 ± 9.1
|
NS
|
|
LVEDP (mm Hg)
|
22.6 ± 2.7
|
22.2 ± 7.5
|
27.4 ± 4.1
|
NS
|
|
LV mass (grams)
|
490 ± 36
|
321 ± 33
|
557 ± 42
|
NS
|
|
AC (minutes)
|
100 ± 5.7
|
102 ± 9.3
|
106 ± 13.4
|
NS
|
|
MT (°C)
|
12.8 ± 0.5
|
12.4 ± 0.6
|
12.7 ± 0.6
|
NS
|
In Table II below: pHo = pH
at onset of AC; pH1 = after 1 hour of AC; pHm = mean integrated pH
throughout AC; pHe = pH at end of AC.
|
|
Group I
|
Group II
|
Group III
|
P (by AOV)
|
|
pHo
|
6.86 ± .07
|
6.95 ± .06
|
6.87 ± .09
|
NS
|
|
pH1
|
6.53 ± .08
|
6.91 ± .07
|
7.17 ± .15
|
<.001
|
|
pHm
|
6.61 ± .06
|
6.90 ± .06
|
7.15 ± .12
|
<.001
|
|
pHe
|
6.44 ± .06
|
6.80 ± .06
|
7. 11 ± . 13
|
<.001
|
These
figures represented an increase in myocardial [H + ] during AC of 252 ± 57
nmoles/1 in Group I, an increase of 90 ±27 nmoles/1 in Group II, and a decrease
of 30 ± 16 moles/1 in Group III (P<.001 between the groups). The
requirements for post CPB inotropic and intraortic balloon support were
significantly lower in Groups II and III compared to Group I (P<0.05). These
data confirm our previous animal experimental observation regarding the
superior metabolic effects of blood over crystalloid CP and indicate that
continuous cold blood K+ cardioplegia is the method of choice in the prevention
of myocardial acidosis during prolonged aortic clamping and in achieving
optimal metabolic protection of the hypertrophied heart.
*By Invitation
34. A No-Flush, Core-Cooling Technique Provides Successful
Cardiopulmonary Preservation for Heart-Lung Transplantation
GEORGE J. KONTOS, JR.*, HIDEO
ADACHI*,
DUKE E. CAMERON*, WILLIAM A.
BAUMGARTNER*,
A. MICHAEL BORKON*, GROVER M.
HUTCHINS*,
JEFFREY BRAWN* and BRUCE A. REITZ
Rochester, Minnesota and
Baltimore, Maryland
One major factor restricting the growth of
clinical heart-lung transplantation has been the inability to provide extended
cold ischemic preservation of the lung. In order to determine whether a
no-flush, core-cooling technique could provide adequate cardiopulmonary
preservation, donor calves (35-50 kg) were placed on cardiopulmonary bypass
(CPB) and rapidly cooled to 15°C during the continuous infusion of
isoproterenol (0.02 mcg/kg/min). In the control group I (N = 5), the heart and
lungs were harvested following the administration of hypothermic cardioplegia
through the aortic root and orthotopically allotransplanted with a total
hypothermic ischemic time of 124 ± 3 minutes. In the preserved group II (N =
5), the heart-lung blocks were similarly excised but stored in a normal saline
bath at 4°C for approximately 4 hours (279 ± 6 minutes) and then transplanted. Both
groups received isoproterenol (0.5-5 mcg/min) during reperfusion and were
studied for 6 hours postimplantation. Myocardial function was assessed by
determining the ratio of the end-systolic pressure to end-systolic dimension
(ESP/ESD), mmHg/mm) using sonomicrometry. Pulmonary preservation was evaluated
by the determination of extravascular lung water with a double-indicator
dilution method (EVLW, ml/kg), arterial oxygenation on 100% FiO2 (PO2, mmHg),
and serial lung biopsies. A blinded histologic lung injury score based upon
pulmonary alveolar-capillary hemorrhage, edema, and necrosis was graded 0 to 4.
The results (mean±SEM) were:
|
Hour
|
Group
|
ESP/ESD
|
EVLW
|
PO2
|
Injury
|
|
0
|
I
|
1.83 ± 0.10
|
8.5 ± 0.8
|
551 ± 18
|
1.6 ± 0.1
|
|
|
II
|
2.16 ± 0.38
|
9.9 ± 1.0
|
567 ± 26
|
1.6 ± 0.1
|
|
2
|
I
|
1.31 ± 0.20
|
10.5 ± 2.1
|
454 ± 34*
|
1.6 ± 0.3
|
|
|
II
|
1.58 ± 0.30*
|
12.1 ± 1.2
|
559 ± 26
|
2.3 ± 0.3*
|
|
4
|
I
|
1.62 ± 0.20
|
9.8 ± 2.2
|
465 ± 28*
|
2.3 ± 0.3*
|
|
|
II
|
1.66 ± 0.40*
|
12.0 ± 1.3
|
454 ± 44
|
2.8 ± 0.2*
|
|
6
|
I
|
1.64 ± 0.41
|
10.5 ± 1.5
|
442 ± 49
|
1.5 ± 0.4
|
|
|
II
|
1.56 ± 0.36*
|
10.5 ± 0.9
|
362 ± 41*
|
2.0 ± 0.6
|
|
*p<0.05 versus respective 0 hour; p<0.05 I versus
II at same hour.
|
Myocardial
and pulmonary function after 4-hour static preservation were similar to
controls. No-flush, core-cooling on CPB provides adequate cardiorespiratory
function following acute bovine heart-lung allotransplantation. By using this
technique, successful cold ischemic cardiopulmonary preservation for heart-lung
transplantation may be achieved.
*By Invitation
35. Proper Donor Selection for Heart-Lung
Transplantation
ARI L.J. HARJULA*, JOHN C. BALDWIN*,
VAUGHN A. STARNES*, EDWARD B.
STINSON, PHILIP
E. OYER*, STUART W. JAMIESON
and NORMAN E. SHUMWAY
Stanford, California and
Minneapolis, Minnesota
Clinical cardiopulmonary
transplantation is currently limited by the availability of suitable heart-lung
donors. Distant graft procurement, using intravenous prostaglandin E-l and
cooling of the graft with pulmonary arterial perfusion, is now clinically
established and should increase the number of available donors. Between March
1981 and September 1986, 40 heart-lung transplantations were performed, and the
characteristics of the donor pool have been analyzed. Donors were intubated for
a mean period of 59 hours (15-140 hours) before harvesting. Eleven donors had
abnormal chest radiographs (28%) and three donors had pulmonary contusion,
noted at the time of graft excision. Gram stain of the donor tracheal aspirate
revealed gram positive bacteria in 80% and gram negative bacteria in 35%. Yeast
was present on fungal smear in 25% of the aspirates. Gram stain of 4 donor
tracheal aspirates revealed heavy polymorphonuclear cells and heavy bacteria
and/or yeast; three of these recipients expired. Staphylococci (42.5%) and
Candida (22.5%) were the most common organisms found on cultures. Thirty
percent (12) of the recipients had early bacterial pulmonary infections and
12.5% (5) had Candida sepsis. Eight of the donors were serologically positive
for cytomegalovirus (CMV), while their recipients were negative; three of these
developed CMV penumonitis. Donor arterial pO2 was less than 100 torr (FIO2
40%) in one patient; this recipient died of lung failure at operation. Severe
deterioration of allograft lung function was seen in 11 recipients (27.5%). Six
of them were associated with substantial post-operative bleeding; 2 were
related to sepsis, 1 to acute rejection, 1 to poor lung function, and 1 to
allograft heart failure. Partial HLA matching was associated with a
statistically insignificant trend toward less obliterative bronchiolitis.
Strict criteria observed for selection of heart-lung donors are valid, and
current graft preservation is adequate. Early morbidity and mortality are
principally related to recipient risk factors; the importance of appropriate
recipient selection is underscored.
*By Invitation
36th Graham Fellow
36. Long-Term Neonatal Heart Preservation (Forum)
HAKOB G. DAVTYAN*, ANTONIO F.
CORNO*,
HILLEL LAKS, SUNITA BHUTA*,
WILLIAM M. FLYNN*,
CRAIG LAIDIG* and DAVIS C.
DRINKWATER*
Los Angeles, California
Donor availability, which is a limiting factor
in neonatal heart transplantation, could be expanded by prolonging safe donor
heart preservation. Thirty-six neonatal (1-5 days) piglet hearts in 6 groups
(Gr) were arrested with cardioplegia, stored for 12 hours at 4°C in storage
solution and reperfused with blood using a support pig. Storage solutions were
normal saline, Sacks II or Sacks II with 20 gm/L glucose (SacksGL). Reperfusion
was carried out with normal blood (NLBL) or modified blood (ModBL) for 20
minutes with superoxide dismutase, catalase, aspartate, glutamate, CPD, K,+
THAM and 50% Dextrose followed by NLBL. Evaluation of stroke work index at
recovery as % of control was performed using the isolated, perfused working
heart preparation after 60 minutes of NLBL perfusion in all groups.
|
|
CARDIOPLEGIA
|
STORAGE
|
REPERFUSION
|
RECOVERY %
|
|
Gr I
|
Stanford
|
Saline
|
NLBL
|
11 ± 8
|
|
Gr II
|
Stanford + Ca + +
|
Saline
|
NLBL
|
8 ± 4
|
|
Gr III
|
Stanford + Ca + +
|
Saline
|
ModBL
|
40 ± 8
|
|
Gr IV
|
Stanford + Ca + +
|
SacksII
|
ModBL
|
47 ± 10
|
|
Gr V
|
Stanford + Ca + +
|
SacksGL
|
ModBL
|
89 ± 10
|
|
Gr VI
|
SacksGL
|
SacksGL
|
ModBL
|
115 ± 11
|
Conclusions: 1) Hypothermic preservation of
the neonatal heart with NLBL reperfusion is poorly tolerated (Gr I and II); 2)
ModBL reperfusion results in markedly improved return of function (Gr III and
IV) (p<0.05); 3) SacksGL storage solution combined with ModBL reperfusion
markedly improves recovery (Gr V) (p<0.05); 4) SacksGL cardioplegia tends to
further improve recovery (Gr VI); 5) Extended preservation of the neonatal
heart is feasible.
10:00 a.m. Intermission - Visit Exhibits - Wacker Hall
*By Invitation
10:40 a.m. Scientific Session - Grand Ballroom
37. Long-Term Hemodynamic Results After Cardiac Transplantation
WILLIAM H. FRIST*, EDWARD B.
STINSON,
PHILIP E. OVER*,
JOHN C. BALDWIN*
and NORMAN E. SHUMWAY
Stanford, California
Although survival rates after cardiac
transplantation have improved since the introduction of Cyclosporine (Cyclo) to
clinical practice in 1980, the long-term hemodynamic results of transplantation
in Cyclo-treated patients is unknown. Annual cardiac catheterization data for
109 Cyclo-treated recipients are compared to that for 65 Azathioprine
(Aza)-treated recipients. All patients underwent at least one annual study.
Age, sex and HLA match were comparable for both groups. At the first annual
study, the Cyclo group had a higher (t-test, P<0.05) mean arterial blood
pressure (MAP, mmHg) (109 ± 1 vs 95 ± 2); mean pulmonary artery pressure (PAP,
mmHg) (17 ± 5 vs 14 ± 5); left ventricular end-diastolic pressure (LVEDP, mmHg)
(12 ± 6 vs 9 ± 4; cardiac index (CI, L/min/sq m) 3.0 ± 0.7 vs 2.6 ± 0.6); and
stroke volume (SV, cc/beat) (66 ± 17 vs 56 ± 14).
At annual study 2, MAP, PAP,
LVEDP, and SV remained higher (P<0.05) for the Cyclo group but CI was
similar for both groups. At study years 3, 4 and 5, PAP, LVEDP, SV and CI were
similar, but MAP remained markedly higher for the Cyclo group (in spite of
aggressive antihypertensive treatment). Ejection fraction was comparable for
both groups at each annual visit.
Analysis of a subset of 34 Cyclo
patients who survived at least 4 years after transplantation showed no
significant time-related changes in hemodynamics over the 5 years of annual
study.
In summary, the long-term
hemodynamic function of the transplanted heart treated with Cyclo is
satisfactory, demonstrates no deterioration over five-year follow-up, and
manifests more systemic hypertension when compared to the Aza-treated group.
*By Invitation
38. Protection of the Ischemic
Lung Using Verapamil and Hydralazine (Forum)
MITSUHIRO HACHIDA *
and DONALD L. MORTON
Los Angeles, California
Little is known about the optimum
treatment of the lung during preservation in preparation for transplantation.
In this study, we evaluated the effect of Verapamil, which has ability as a Ca2
+ channel blocker and vasodilator, and Hydralazine, which has only vasodilator
activity, compared with a non-treated control. Twenty-three dogs were used and
after the left hilar structures were exposed, the pulmonary artery, vein and
bronchus were clamped. The lungs of eight dogs in Group A were perfused with
200 ml of Collins & Sacks (C-S) solution alone by gravity at 40 cm pressure
at the initial and terminal phases. By contrast, the lungs were identically
perfused with C-S solution containing 20 mg of Hydralazine in seven dogs in
Group B and with 5 mg of Verapamil in eight dogs in Group C. The left lung in
each dog was exposed to normothermic ischemia (28°C) for 30 minutes to 5 hours
and pulmonary circulation was re-established. To detect the functional recovery
of the left lung alone, the right main bronchus was ligated. The mean ischemic
time was 2.3 hours in Group A, 2.9 hours in Group B, and 3.1 hours in Group C.
The percentage of survivors was 12.5% in Group A, 25% in Group B, and 88% in
Group C. Po2 tension in room air after the bronchial ligation was 39.9 ± 10.2
in Group A, 59.2 ± 32.2 in Group B, 76.1 ± 32.9 in Group C. Statistical
significance existed between Groups A and C (p<0.05). Lung perfusion
scintigraphy after the experiment showed greater perfusion in Group C compared
with Groups A and B. Pulmonary vascular resistance after bronchial ligation was
428.9± 158.8 in Group A, 219.9 ± 51.9 in Group B, and 208.3 ± 84.5 in Group C.
The released enzymes, GOT, CPK, LDH, after reperfusion were measured by the
level of enzymes in the pulmonary vein using PV-PA gradient. Each enzyme was
significantly less in Group C than in Groups A and B (p<0.01). Thus, tissue
damage due to ischemia was significantly less using Verapamil than the
vasodilating drug, Hydralazine. Therefore, inhibition of Ca2 +
influx is the major factor which prevents injury of the pulmonary vascular tree
due to ischemia following reperfusion rather than the vasodilating effect of
this drug.
*By Invitation
39. A Simple Technique for Multi-Organ Preservation (Forum)
SUFAN CHIEN*,
EDWARD P. TODD and
JOHN DIANA *
Lexington, Kentucky
We report here a simple
self-perfusing, self-cleaning preparation for multi-organ preservation with no
ischemic time. In five mongrel dogs, after anesthesia, a mid-line incision was
made. The abdominal aorta and IVC were divided below the renal arteries. The
heart and lung were separated and removed with liver, pancreas, kidneys, and a
portion of small intestine en bloc while they were self-perfused. The
preparation was perfused by the heart, and a respirator was used. Arterial and
venous pressures were measured through indwelling catheters. Fresh blood 10%
glucose 500 ml, plus Insulin 50 units, KC1 2/mg/ml, CaCl2 2mg/ml,
Mannitol 20 mg/ml, and Prednisolone 125 mg were
dripping slowly through a catheter into the portal vein. One ml of 20% soyacal
was administered every two hours. Organs were experimentally perfused for an
average of 12 hours. Hemodynamic and lab tests are summarized in the figure
below. AOSP ranged from 75-125 mm Hg, CVP 0-5 mm Hg, portal VP 0-3 mm Hg, bile
output 5-20 ml/ hour, urine output 10-70 ml/hour, hematocrit 35-55%. The heart
and lungs were normal and physiologically functional at 12 hours. The pancreas
and small intestine appeared normal by observation. In 3 dogs, the liver showed
some congestion which might be related to the special anatomy of the portal
vein in dogs. The kidney appeared to have edematous swelling after 16 hours.
The following features seem to characterize this procedure: 1) no ischemic
time; 2) the preparation is physiologically self-sufficient and requires only
ventilation and IV fluids; 3) the preparation appears suitable for distant
procurement; and 4) additional tissues and organs can be attached to study
their effect on preservation and overall physiological function. We believe
this is the first report of multiple organ preservation employing
auto-perfusion technique. Although the data are preliminary, the results are
very promising and deserve further evaluation.
*By Invitation
40. Role of the Antibody to Vascular Endothelial Cells in Hyperacute
Rejection in Patients Undergoing Cardiac Transplantation (Forum)
ALFREDO TRENTO*, ROBERT L.
HARDESTY,
BARTLEY P. GRIFFITH, TONY ZERBE*,
ROBERT L. KORMOS* and HENRY T.
BAHNSON
Pittsburgh, Pennsylvania
A positive lymphocytotoxic cross-match has
been a contraindication to transplantation because of the possibility for
hyperacute rejection. However, 12 of 275 heart transplant recipients had a positive
lymphocytotoxic cross-match and only one of them died of hyperacute rejection.
We also identified 6 patients in whom, despite a negative direct
lymphocytotoxic cross-match, acute failure of the cardiac homograft was
associated with histologic and immunologic findings consistent with hyperacute
rejection. The patients' sera were found to have antibodies reacting against
vascular endothelial cells and against concordant monocytes. The same sera did
not show any reactivity against B or T lymphocytes. In these 6 patients the
transplanted heart failed in either the operating room (4 patients), or within
the first 6 postoperative hours (2 patients) with a pattern of severe
biventricular failure: CVP >20 mm Hg, PCW >20 mm Hg and marked systemic
hypotension despite massive in-otropic support. Two of the patients could be
retransplanted within 6 and 8 hours respectively, but the second homograft
failed acutely in both. In a third patient the failure of the first cardiac
homograft was followed by insertion of a Jarvik-7 artificial heart. Successful
retransplantation followed multiple plasmapheresis which were later found to
eliminate anti-vascular endothelial cell (VEC) antibodies from the recipient's
serum. Histologically the failing homografts showed many small vessels with
endothelial damage, platelet-fibrin thrombi occluding arterioles, occasional
small foci of myocar-dial necrosis and poly-morphonuclear granulocyte
infiltrates. Direct immunofluorescence revealed the presence of IgM and C3
complement bound to the endothelium of numerous small and large vessels. This
anti-VEC antibody was not found in a group of 17 patients who experienced an
uneventful clinical course following cardiac transplantation. When the donor's
tissue was available, donor's specific analysis revealed the presence in the
recipient's serum of preformed and-VEC antibody that bound to the epithelium of
the donor aorta and vena cava. While the role of anti-VEC specific antibody in
cardiac transplantation awaits further evaluation, these data strongly support
the hypothesis of hyperacute rejection related to preexisting anti-VEC
antibody.
11:30 a.m. Basic Science Lecturer
"IMMUNO-REGULATION:
THE KEY TO TRANSPLANTATION AND AUTOIMMUNITY"
Gustav J.V. Nossal, M.D.,
Melbourne, Victoria, Australia
Supported in part by an
Educational Grant from the Coordinating Committee for Continuing Education in
Thoracic Surgery. (CCCETS)
12:15 p.m. Adjourn for Lunch
*By Invitation
