TUESDAY MORNING, APRIL 25, 1995
7:00 am FORUM SESSION I
Auditorium, Hynes Convention Center
Moderators: Andrew S. Wechsler, M.D.
Douglas J. Mathisen, M.D.
F1. INHALED NO FAILS TO CONFER THE
PULMONARY PROTECTION PROVIDED BY DISTAL STIMULATION OF THE NO PATHWAY AT THE
LEVEL OF CGMP
Yoshifumi Naka, M.D., Ph.D.*,
Dillip K. Roy, M.D.*, Arthur J. Smerling, M.D.*, Robert E. Michler, M.D.*,
Craig R. Smith, M.D., David M. Stern, M.D.*, David J. Pinsky, M.D.* and Mehmet
C. Oz, M.D.*
New York, New York
Inhalation of
nitric oxide (NO) gas effectively lowers pulmonary vascular resistance (PVR) in
the adult respiratory distress syndrome, and some have suggested that it may be
beneficial following lung transplantation. However, during reperfusion, NO
combines rapidly with superoxide to form highly toxic peroxynitrite. We
hypothesized that distal stimulation of the NO/cGMP pathway at the level of
cGMP might confer the beneficial vascular effects of NO without its potential
toxicities. To test this hypothesis, we used a recently described orthotopic
rat left lung transplant model in which hemodynamic and survival measurements
can be obtained independent of the native lung. Three conditions were tested:
(1) Control (EC preservation solution), (2) Inhaled NO (EC
preservation solution but inhaled NO given to recipient), and (3) EC
preservation solution supplemented with the membrane permeable, nonhydrolyzable
cGMP analog [8-(4-chlorophenylthio)-guanosine-3',5'-cyclic
monophosphate; cGMP, 250 |iM]. The left lung was harvested from 22 male Lewis
rats, preserved for 6 hrs at 4° C, and transplanted into isogenic recipients
using cuff technique for all anastomoses. All recipients were ventilated with
70% ©2 and 30% N2 (as the carrier gas for NO was N2), which was supplemented
with NO (65 ppm, monitored by chemiluminescence) in the second group. Gas
mixtures were begun immediately prior to cross-clamp release and continued
throughout reperfusion. In all experiments, the native (right) PA was ligated
immediately after placement of a PA flow probe and Millar catheters into the LA
and PA. PA flow (mL/min), arterial oxygenation (pO2, mm Hg) graft neutrophil
infiltration (myeloperoxidase activity; MPO, A absorbance/min at 460 nm) and
recipient survival (%) at 30 min. were measured. PVR (WU x 1000) was
calculated. (Means ± SEM are shown; *=p<0.05 vs control, **=p<0.01 vs
control; t=p<0.05 vsNO).
|
|
PVR
|
pO2
|
MPO
|
Survival
|
|
Control (n=6)
|
12.1 ± 2.6
|
82.2 ± 20
|
3.1 ± 0.2
|
0%
|
|
NO (n=12)
|
6.5 ± 1.4
|
170 ± 50
|
2.9 ± 0.2
|
33%
|
|
cGMP (n=4)
|
1.1 ± 0.1*
|
369 ± 28*
|
1.7 ± 0.1*
|
100%**
|
Only the cGMP analog was
associated with reduced PVR, improved pO2, reduced graft neutrophil
infiltration, and improved recipient survival. These data suggest that
stimulation of the NO/cGMP pathway at the level of cGMP has a protective effect
that is not seen with inhaled NO in the immediate pulmonary reperfusion period.
Robert E. Gross Research Scholar
*By invitation
F2. DIRECT EFFECTS OF 3,5,3'
TRIIODO-L-THYRONINE (T3) ON MYOCYTE CONTRACTILE PROCESSES: INSIGHTS
INTO MECHANISMS OF ACTION
Jennifer D. Walker, M.D.*, Rupak
Mukherjee, M.S.*, Fred A. Crawford, M.D. and Francis G. Spinale, M.D., Ph.D.*
Charleston, South Carolina
Administration
of 3,5,3' triiodo-L-thyronine (T3) in the setting of congestive
heart failure and cardiopulmonary bypass has been suggested to improve left
ventricular (LV) function; however, the cellular basis for this improvement
remains unknown. Accordingly, the present study examined the direct effects of
T3 administration on myocyte function and the contributory
mechanisms for these effects. In isolated porcine LV myocytes (n=81), velocity
of shortening increased in the presence of 80 pM T3 compared to
baseline (77.1±3.3 vs 117.0±5.0 jam/sec, p<0.05). In a separate series of
experiments (n=29), pre-treatment with 80 pM T3 increased
P-adrenergic response (pAR: 25 nM isoproterenol) compared to PAR alone
(203.7±16.2 vs 274.3±16.9 |im/sec, p<0.05). In isolated myocyte preparations
(n=9), cyclic-AMP production (fmols/myocyte) was measured. Cyclic-AMP was
unchanged with T3, but T3 pretreatment with PAR increased
cyclic-AMP compared to PAR alone.
|
|
Baseline
|
80 pM T3
|
ßAR
|
80 pM T3 + ßAR
|
|
Cyclic-AMP
|
24.7±5 8
|
39 1±8 3
|
120 1±35.5*
|
224.4±61 1*+#
|
|
L-type Ca2+
Current Density
|
-3 63±0.28
|
-3.76±0 18
|
-6.27±0 99*
|
-8.90±0.66*+#
|
|
Peak Intracellular Ca2+
|
159.9±3.9
|
159.6±5.7
|
179.9±10.1*
|
185.5±9.3*+#
|
|
|
*p<0 05 vs baseline, +p<0.05 vs T3,
#p<0 05 vs ßAR
|
Since cyclic-AMP modulates
intracellular Ca2+ processes, L-type Ca2+ processes,
L-type Ca2+ channel density (patch clamp methods; pA/pF, n=15) and
peak Ca2+ release from the sarcoplasmic reticulum (Fura-2 ionic
measurement, pM, n=46) were measured. T3 pretreatment followed by
PAR increased L-type Ca2+ channel current and intracellular Ca2+
compared to PAR alone. The unique findings from this study are twofold. First,
T3 stimulates steady state myocyte contractile function by a
cyclic-AMP independent mechanism. Second, T3 potentiates the effects
of PAR by increasing cyclic-AMP and subsequent phosphorylation of L-type Ca2+
channels. Thus, T3 enhanced PAR transduction with resultant
increased Ca2+ availability and improved myocyte inotropic response.
These findings suggest the T3 may provide a unique adjunct to
conventional P-adrenergic agonist therapy in the clinical setting.
Nina S. Braunwald Research Fellow
*By Invitation
F3. INFLUENCE OF VEIN VALVES IN THE
DEVELOPMENT OF ARTERIOSCLEROSIS IN RABBIT VENO-ARTERIAL GRAFTS
Aurelio Chaux, M.D.*, Xin Min
Ruan, M.D.*, Michael C. Fishbein, M.D.* and Jack M. Matloff, M.D.
Los Angeles, California
Purpose:
To study the influence of vein valves and define possible mechanisms for
the formation of arteriosclerotic lesions in veno-arterial grafts.
Methods:
Jugular vein grafts were interposed into the carotid circulations of 48
hypercholesterolemic rabbits. In 24 animals (Group A), vein segments did not
contain vein valves; in another 24 (Group B), a vein valve was present.
Subgroups of 6 animals were sacrificed at 2, 4, 6 and 8 weeks. Two mm sections
were fixed in 4% paraformaldehyde and placed in sucrose for morphology and
morphometry or frozen for immunohistochemistry and in situ hybridization for
growth factor expression. Morphometry was done with computer-based image
measuring software (Optimas) and validated by manual planimetry in 70% of animals.
Cell identification and couting was done by immunohistochemistry. Dependent
variables: graft mean area, mean thickness and proliferated cell nuclear
antigen. Independent variables: presence or absence of vein valves and time in
weeks post surgery. Measurements of mean area and thickness at cross sections
were made just before and after the valve in Group B. Post valve values were
also compared with those in the middle of the graft of Group A animals. Paired
t-test and regression analysis were used.
Results:
At 2 weeks intimal and medial thickening were due to an increase in cell
number. From 2 to 6 weeks further intimal and medial thickening occurred
without additional increase in cell number. At 6 weeks, foam cells and lipid
deposits appeared, and at 8 weeks changes identical to human arteriosclerotic
plaques were evident. Changes developed sooner and more intensely in Group B
animals (p<001), and segments immediately after the valve developed them
faster and more severely than before the valve (p<.001). PCNA staining
showed greater cell proliferation in the post-valve segments (p<.001).
Endothelial and intimal growth factor expression was strong for IGF-1 and EOF,
mild for PDGF.
Conclusions:
The presence of vein valves augments and accelerates intimal hyperplasia
and arteriosclerosis, and at least 3 growth factors may be involved in the
development of these lesions. To our knowledge, this is the first controlled
experiment that demonstrates this phenomenon.
*By invitation
F4. MYOCARDIAL STUNNING: A THERAPEUTIC
CONUNDRUM
Zhandong Zhou, M.D.*, Robert D.
Lasley, Ph.D.*, Rolf Bunger, M.D, Ph.D.*, Julia Hegge, B.S.* and Robert M.
Mentzer, Jr., M.D. Madison, Wisconsin and Bethesda, Maryland
Dobutamine (DOB) and pyruvate (PYR) are two potent
inotropic agents with different mechanisms of action. While both can be used to
treat post-ischemic myocardial dysfunction, the potential deleterious effects
of augmenting myocardial contractility in the setting of myocardial stunning
has not been addressed. To test the hypothesis that these agents may have
adverse effects on the stunned heart, systolic wall thickening (SWT),
myocardial phosphorylation potential index (CrP/CrxPj), interstitial fluid
adenosine (ISF [ADO]) and myocardial oxygen consumption (MV02) were measured in
open chest pigs. SWT was measured using sonomicrometry, and microdialysis
probes were inserted to estimate ISF [ADO]. Stunning was induced with a 10 min
occlusion of the anterior descending coronary artery. After 30 min reperfusion,
pigs were treated with either DOB (10 jig/kg/min) or PYR (1 ml/min or a 150 mM
solution). Results expressed as mean±SEM; *p<0.05 vs control,
фp<0.05 vs stunned.
|
Dobutamine Treatment (N=7)
|
|
Pyruvate Treatment (N=7)
|
|
|
SWT
(% Baseline)
|
ISF[ADO]
(µM)
|
MVO2
(ml/min/100g)
|
|
|
SWT
(% Baseline)
|
ISF [ADO]
(µM)
|
MVO2
(ml/min/100g)
|
Control
|
100
|
0.47 ± 0.05
|
7.27 ± 0.22
|
|
Control
|
100
|
0.63 ± 0.05
|
7.10 ± 0.24
|
|
Stunned
|
31.2 ± 1.0*
|
0.42 ± 0.04
|
7.17 ± 0.7
|
|
Stunned
|
31.0 ± 4.5*
|
0.58 ± 0.08
|
6.71 ± 03
|
|
10'DOB
|
57.3 ± 5.4*ф
|
7.5 ± 0.09*ф
|
12.03 ± 1.4*
|
|
10' PYR
|
75.2 ± 10.8*ф
|
0.57 ± 0.07
|
7.27 ± 0.16
|
|
20' Post DOB
|
23.7 ± 1.8*ф
|
0.45 ± 0.71
|
7.57 ± 0.71
|
|
20' Post PYR
|
30.0 ± 4.8*
|
0.54 ± 0.07
|
7.05 ± 0.2
|
DOB produced myocardial
de-energization, as the CrP/ CrxPi. ratio decreased from 0.17±0.02
to 0.09±0.02 (p<0.02) in the stunned hearts. In contrast, PYR enhanced
myocardial energy status, since the ratio increased from 0.20±0.03 to
0.55±0.08(p<0.01).
Infusion of
both inotropic agents resulted in a marked improvement in regional SWT. The
dobutamine effect, however, produced a marked increase in MVO2
associated with an expected rising ISF [ADO] due to the decline in the CrP/CrxPi.
This energetic stress may account for the further deterioration in cardiac
function observed after cessation of DOB. In contrast, PYR improved postischemic
contractile function and enhanced myocardial energetics. These experimental
findings suggest that under certain circumstances the clinical use of ß
receptor agonists to treat myocardial stunning after cardiac surgery or heart
transplantation may be suboptimal, if not undesirable. Further investigation is
warranted to determine the optimum threapy for the stunned heart.
*By invitation
F5. PRECONDITIONING WITH POTASSIUM CHANNEL
OPENERS: A NEW CONCEPT FOR ENHANCING CARDIOPLEGIC PROTECTION
Philippe Menasche, M.D., Ph.D.,
Egidijus Kevelaitis, Ph.D.*, Christian Grousset, M.D., Ph.D.*, Armand Piwnica,
M.D. and Gerard Bloch, M.D.*
Paris, France
Background. Preconditioning
(PC) is now recognized as one of the most effective means of improving the tolerance
of myocardium to a sustained episode of ischemia. It has been suggested that
this protection could result from an adenosine-induced opening of adenosine
triphosphate-sensitive potassium channels and the related limitation of calcium
overload.
Objective. This
study was therefore designed to assess whether the protective effects of
ischemic PC can be mimicked by the administration of a potassium channel opener
in the surgically relevant setting of global myocardial ischemia.
Methods. Forty
isolated isovolumic rat hearts were subjected to 45 minutes of normothermic
potassium arrest followed by 1 hour of reperfusion. Hearts were randomly
divided into four equal groups that only differed by the modalities of the
prearrest treatment protocol: group 1 had no prearrest intervention (controls);
group 2 hearts were preconditioned with 5 minutes of global ischemia followed
by 5 minutes of buffer reperfusion prior to the onset of potassium arrest; in
group 3, the preconditioning stimulus consisted of a 5-minute infusion of the
potassium channel opener nicorandil (lOpM) followed by 5 minutes of drug-free
buffer perfusion prior to potassium arrest; in group 4, the same protocol as in
group 3 was used except that the administration of nicorandil was preceded by a
5-minute infusion of the selective potassium channel blocker glibenclamide
([glib]10|aM). During arrest, the left ventricular balloon was kept inflated to
monitor the time course of ischemic contracture.
Results. They
are summarized below (data analysis by 2-way ANOVA with repeated measures).
|
Group
|
Diastolic Pressure (mmHg)
|
LV dP/dt (mmHg/sec-1)
|
|
|
Baseline
|
Reperfusion
|
Baselin e
|
Reperfusion
|
|
1 (controls)
|
9.6 ± 0.6
|
53.5 ± 2.9
|
4,745 ± 170
|
1,599 ± 99
|
|
2 (ischemic PC)
|
9.2 ± 0.7
|
29.7 ± 3.1*°
|
4,570 ± 167
|
2,970 ± 141**
|
|
3 (nicorandil PC)
|
9.1 ± 0.3
|
29.0 ± 1.4*#
|
4,767 ± 161
|
2,724 ± 105**
|
|
4 ((nicorandil+ glib)
|
11. 3 ± 0.9
|
46.2 ± 2.4
|
5,002 ± 117
|
1,965 ± 77
|
|
*P<0.0001 vs group 1
|
° P<0.0002 vs group 4
|
** P<0.0001 vs groups 1
& 4
|
|
#P<0.0001 vs group 4
|
|
|
|
|
|
All data are mean ± SEM
|
|
|
|
|
|
|
|
|
|
|
|
Pretreatment
with nicorandil also lowered peak contracture during arrest significantly (40.4
± 2.1 mmHg vs 51.8 ± 3.0 mmHg in controls [P<0.01 vs nicorandil], 50.0 ± 2.8
mmHg in ischemically preconditioned hearts [P<0.01 vs nicorandil] and 54.9 ±
5.3 mmHg in nicorandil+glibenclamide-treated hearts [P<0.01 vs nicorandil])
and lengthened the time to peak contracture, as compared with the control and
nicorandil+glibenclamide groups (2,066 ± 45 sec vs 1,806 ± 91 sec [P<0.03]
and 1,573 ± 104 sec [P<0.001], respectively).
Conclusion. The
protective effects of ischemic PC can be mimicked by a pharmacological opening
of adenosine triphosphate-sensitive potassium channels. The surgical relevance
of these data stems from (1) the possibility to plan the onset of aortic
cross-clamping and, consequently, to implement a PC stimulus in a timely
appropriate fashion, and (2) the approval of nicorandil for clinical use in
patients with coronary artery disease.
*By invitation
F6. THE ROLE OF NITRIC OXIDE IN CEREBRAL
RECOVERY AFTER CARDIOPULMONARY BYPASS WITH DEEP HYPOTHERMIC CIRCULATORY
ARREST IN INFANT PIGLETS
Takeshi Hiramatsu, M.D.*, Takuya
Miura, M.D.*, Adre Duplessis, M.D.*, Masahiro Tanji, M.D.*, Joseph M. Forbess,
M.D.*, Miles K. Tsuji, M.D.*, David Holtzman, M.D.* and Richard A. Jonas, M.D.
Boston, Massachusetts
Although nitric
oxide (NO) is neurotoxic in vitro, there is continuing controversy regarding
the role of NO in global cerebral ischemia. The effects on brain metabolic
recovery of L-arginine (L-arg), a NO precursor, and L-Nitro-Arginine Methyl
Ester (L-NAME), a NO synthase inhibitor, have been studied in an infant piglet
model of deep hypothermic circulatory arrest (DHCA).
METHODS: Forty
2-week old piglets underwent core cooling to 15°C, 1 hour of DHCA at 15°C, 45
minutes of rewarming and 3 hours of normo-thermic reperfusion. Group L-arg
(n=10) received 30 mg/kg of L-arginine IV before cardiopulmonary bypass (CPB)
and 10 mg/kg/min infusion during the first 1 hour of reperfusion (Rep). Group
L-NAME 10 mg/kg (n=10) received 10 mg/kg of L-NAME IV before CPB. Group
L-NAME+L-arg (n=10) received both L-NAME and L-arg as in the first two groups.
Control (n=10) received no medication. Recoveries of cerebral high energy
phosphates and pHi were assessed by magnetic resonance spectroscopy in half of
the animals in each group. Cerebral blood flow (CBF) and cerebral vascular
resistance (CVR) by microspheres, cerebral metabolic rates of oxygen and
glucose, and the redox state of cytochrome a,a3 by near infrared spectroscopy
were assessed in the rest. Brain water content was measured in all animals
after the experiments.
RESULTS: Results
are given as mean±SEM. *p<0.05 vs. Control by Student-Newman-Keuls test
|
|
min. Rep
|
Control
|
L-arginine
|
L-NAME
|
L-NAME+
|
|
|
|
|
|
|
L-arginine
|
|
ATP
|
45
|
73.7 ± 15.9
|
83.5 ± 6.2
|
28.3 ± 4.3*
|
45.9 ± 5.4
|
|
(% recovery)
|
225
|
71.5 ± 5.0
|
84.3 ± 2.7*
|
32.0 ± 2.6*
|
33.2 ± 5.8*
|
|
pHi
|
45
|
6.75 ± 0.05
|
6.79 ± 0.05
|
6.62 ± 0.03
|
6.63 ± 0.05
|
|
(Unit)
|
225
|
7.23 ± 0.11
|
7.28 ± 0.04
|
6.88 ± 0.06*
|
6.95 ± 0.13
|
|
Cytochrome a,a3
|
45
|
-7.0 ± 1.1
|
-2.3 ± 1.3*
|
-11.2 ± 1.2
|
-11.1 ± 2.3
|
|
(|iM x DPF)
|
225
|
0.4 ± 0.8
|
1.0 ± 1.4
|
-12.2 ± 0.9*
|
-10.5 ± 3.8*
|
|
Mean arterial
|
45
|
45.2 ± 4.1
|
44.2 ± 3.7
|
80.0 ± 9.6*
|
67.4 ± 6.5
|
|
Blood pressure (mmHg)
|
225
|
121 ± 8
|
112 ± 7
|
154 ± 10*
|
146 ± 11*
|
|
CBF
|
45
|
17.3 ± .3
|
32.6 ± 5.9*
|
20.7 ± 4.5
|
16.4 ± 1.0
|
|
(mL/min/100g)
|
225
|
50.6 ± 4.7
|
59.3 ± 9.6
|
47.3 ± 4.5
|
49.2 ± 5.2
|
|
CVR
|
45
|
3.20 ± 0.43
|
2.02 ± 0.35
|
5.17 ± 1.48
|
3.95 ± 0.23
|
|
(unitx 100g)
|
225
|
2.14 ± 0.17
|
1.96 ± 0.22
|
3.57 ± 0.45*
|
3.19 ± 0.16*
|
|
Brain water content
|
|
81.8 ± 0.3
|
81.8 ± 0.2
|
82.7 ± 0.1*
|
82.4 ± 0.2
|
SUMMARY: L-arginine
improved recovery of cerebral ATP, cyto-chrome a,a3 oxidation and cerebral
blood flow. L-NAME reduced recovery of cerebral ATP, pHi and cytochrome a,a3
oxidation and increased mean blood pressure, CVR and brain water content. These
effects of L-NAME were minimally reversed by L-arginine infusion after
reperfusion.
CONCLUSIONS:
The net effect of intra-neuronal and endothelial nitric oxide is to promote
cerebral metabolic recovery after global ischemia.
*By invitation
F7. THE EFFECTS OF RETROGRADE CEREBRAL
PERFUSION AFTER PARTICULATE EMBOLIZATION TO THE BRAIN
Mustafa E. Yerlioglu, M.D.*,
Craig K. Mezrow, M.S.*, All M. Sadeghi, M.D.*, Peter S. Midulla, M.D.*, Ning
Zhang, M.D.*, Howard H. Shaing, D.V.M.*, Donald J. Weisz, Ph.D.* and Randall B.
Griepp, M.D.
New York, New York
Neurologic
injury as a consequence of cerebral embolism of air or atherosclerotic debris
during cardiac and aortic surgery remains a major cause of morbidity. We have
developed a chronic porcine model to evaluate the potential of retrograde
cerebral perfusion (RCP) for improving cerebral outcome following cardiac
surgery, and have previously demonstrated that it results in a small amount of
nutritive flow, and provides cerebral protection superior to prolonged
hypothermic circulatory arrest. We designed the current study to evaluate the
efficacy of RCP in mitigating the effects of cerebral embolism of paniculate
matter during cardiac surgery.
Four groups of
pigs (20-28 kg) were assigned to undergo deep hypothermia at an esophageal
temperature of 20°C: a retrograde control group (RC, n=5); a retrograde
embolism group (RE, n=10); an antegrade control group (AC, n=5); and an
antegrade embolism group (AE, n=6). The sagittal sinus (SS) was cannulated in
all animals, and flow in the SVC was regulated in order to achieve and maintain
a SS pressure of 30 mmHg during RCP. During ante-grade perfusion, the aortic
arch pressure was maintained at 50 mmHg. Polystyrene microspheres, (250-750 um,
200 mg), were utilized as the embolic material. In the embolism groups, the
spheres were injected via a cannula in the isolated arotic arch; controls were
injected with 10 cc of saline. Five minutes after injection, antegrade
perfusion was continued in antegrade groups, and retrograde perfusion via an
SVC cannula was instituted in the retrograde groups, both for a duration of 25
minutes. Blood returning to the aortic arch was collected and measured in the
RCP groups. All animals were allowed to recover for at least five days and were
evaluated daily using a quantitative behavioral score, in which 9 indicates
complete normalcy, 7 means that the animals were able to stand unassisted and
were likely to recover fully, and lower numbers indicate substantial injury,
with 0=death. At the time of elective sacrifice, half of the brain was utilized
for recovery of embolized spheres after digestion with ION NaOH.
As shown in the table, neurological recovery in the
control groups was complete with retrograde as well as with antegrade
perfusion. Following embolization, there was severe neurological injury in both
groups, and both antegrade and retrograde flows were reduced compared with
controls. Although fewer spheres were present in the brains of the RE group,
neurologic outcome was no better in the group as a whole then in the AE group.
When the RE group was examined in greater detail, however, it was seen that
some animals recovered almost completely after retrograde perfusion
(score>7, good outcome). Further scrutiny showed that these good outcome RE
animals required significantly lower SVC pressure to achieve adequate SS
pressures than the animals that sustained severe neurologic injury following
embolization and RCP. Although the mechanism of the injury following use of
high SVC pressures during RCP after embolization (but not in controls) remains
unclear, our data suggest that RCP during cardiac surgery may mitigate cerebral
injury from participate emboli if adequate RCP can be achieved using SVC
pressure <40 mmHg.
|
|
|
|
Aortic Arch
|
SVC
|
Behavioral
|
Spheres
|
Group
|
n
|
Flow Rate
|
Return Rate
|
Pressure
|
Score
|
in Brain
|
|
|
|
(ml/kg/min)
|
(ml/kg/min)
|
(mmHg)
|
0-9)
|
(mg)
|
AC
|
5
|
11.0 ± 3.1
|
|
|
8.8 ± 0.6
|
|
|
RC
|
5
|
34.7 ± 32.7
|
0.8 ± 0.4
|
53.8 ± 23.6
|
9.0 ± 0.0
|
|
|
AE
|
6
|
5.1 ± 1.0a
|
|
|
5.2 ± 2.7ab
|
1.9 ± 1.3c
|
|
RE
|
10
|
17.5 ± 10.3
|
0.5 ± 0.2
|
48.4 ± 19.2
|
5.9 ± 2.8ab
|
0 ± 0.4c
|
|
RE Good Outcom
|
4
|
10.3 ± 0.4
|
0.5 ± 0.1
|
33.7 ± 3.9
|
8.5 ± 0.6
|
0.8 ± 0.2
|
|
RE Poor Outcome
|
6
|
22.3 ± 11.1
|
0.4 ± 0.2
|
58.2 ± 19.1
|
4.2 ± 2.2
|
0.8 ± 0.5
|
|
Mean values ± STD Deviation
|
a: p<0.05 vs. AC
|
c: p<0.05 AE vs. RE
|
|
|
|
|
b: p<0.05 vs. RC
|
|
|
|
|
|
|
|
|
|
|
F8. EFFECTS OF CARDIOPLEGIA ON VASCULAR
FUNCTION AND THE NO-REFLOW PHENOMENON FOLLOWING ISCHEMIA-REPERFUSION:
STUDIES IN THE ISOLATED BLOOD-PERFUSED RAT HEART
Vincenzo Argano, M.D., FRCS*,
Manuel Galinanes, M.D., Ph.D.*, Stephen J. Edmondson, MRCP, FRCS* and David J.
Hearse, Ph.D., D.Sc.*
London, United Kingdom
Sponsored by: Mark V.
Braimbridge, London, United Kingdom
The protective role of cardioplegia against
post-ischemic cardiac dysfunction is well established. However, the effect of
cardioplegia on vascular function and its repercussion on the no-reflow
phenomenon are controversial. We have investigated the influence of St. Thomas'
cardioplegic solution on: (i) endo-thelium-dependent and
endothelium-independent vascular function (EDVF and EIVF), and (ii) the extent
of the no-reflow phenomenon. Isolated rat hearts (n=16/group) perfused with
blood at 60 rnmHg, were subjected to 10, 20, 30 or 40 min of global ischemia
and 40 min of reperfusion (37°C). Eight hearts in each group also received
cardioplegia (40 mmHg for 2 min) before ischemia. At the end of reperfusion, a
bolus of 250ug (3mM) of nitro-L-arginine methyl ester was infused to assess
EDVF. After 20 min washout, 25ug (0.3mM) of sodium nitroprusside was infused to
assess EIVF. Fluorescein (1 ml, 1% w/v) was then infused to assess no-reflow.
Hearts were frozen, cut into transverse sections (lOxlmm), video-recorded under
UV light, and images digitised and analysed for density of fluorescence.
No-reflow was defined as a flow <5% (corresponding to 171-256 grey-scale
density). EIVF (percent of non-ischemic control) was severely decreased only
after 30 min and 40 min of ischemia (45. ± .6% and 31. ± 2.5%; p<0.05), but
was significantly protected by cardioplegia (62. ± .7% and 57. ± .9%). A
significant reduction in EDVF was only observed after 40 min of ischemia (69. ±
0.6%; p<0.05) and again this was improved by cardioplegia (89. ± .8%). Areas
of no-reflow were present after 30 and 40 min of ischemia (11. ± .8% and 33. ± 4.1%
of LV mass) and they were significantly decreased by cardioplegia (0. ± .4% and
3. ± .6%; p<0.05). In conclusion, cardioplegia protects against
post-ischemic endothelium-dependent and endothelium-independent vascular
dysfunction and reduces the extent of no-reflow.
*By invitation
9:00 am PLENARY SESSION
Auditorium, Hynes Convention Center
Moderators: Robert B. Wallace, M.D.
James L. Cox, M.D.
15. SURGICAL MANAGEMENT OF EXTENSIVE
CALCIFICATION OF THE MITRAL
VALVE ANNULUS
Alain F. Carpentier, M.D., Ph.D., Jean-François
Fuzelier, M.D.*, John Y.M. Relland, M.D.* and Michel Pellerin, M.D.*
Paris, France
Extensive
calcification of the mitral valve annulus (MVA) is a pathological entity
frequently associated with degenerative valvular disease. The calcification
process involves at least 1/3 of the circumference of the MVA and usually not
the valvular tissue. It may extend however to the underlying myocardium.
Whenever an operation is necessary for an associated valve insufficiency, the
question arises whether it is preferable to repair or to replace the valve and
how to manage the calcification. This paper reports the technical details, the
recent improvement and the mid-term results of a reconstructive operation
proposed in 1986 which up to now has only been the object of early and brief
reports on small series. This operation comprises the temporary detachment of
the corresponding leaflets, en bloc resection of the calcium deposit with its
surrounding fibrous capsula, annular reconstruction and valve repair. For
patients in whom the calcification process extends to the myocardium, a
modified operation has been more recently developed which comprises in addition
a "sliding plasty" of the left atrium over the area of resected calcium.
Between 1986
and 1994, among 63 patients (pts) with extensive calcification of the annulus
and severe mitral valve insufficiency, 62 benefited from these techniques of
repair. Ages ranged from 18 to 81 years (mean 62). Twenty-eight pts had a
billowing mitral valve (Barlow), 32, a fibroelastic deficiency and 2, Marfan's
disease. The calcification involved 1/3 of the annulus in 26 pts, 2/3 in 34 pts
and the whole annulus in 2 pts. In 8 pts, the calcification process extended to
the papillary muscles (4 pts) and/or deeply within the myocardial wall (6 pts).
There were 2 hospital deaths (3.2%) and no early reoperation. The follow-up
period extended from 4 months to 8 years (mean 3 years 8 months). There were 2
late deaths, 2 and 17 months after the operation (one valve related) for an actuarial
survival of 95.7% at 7 years.
Late
reoperation (3 to 62 months) was necessary in 4 pts (6.4%) for residual mitral
valve incompetence (MVI) (n=2), hemolysis (n=1) or endocarditis (n=1). In one
of these pts, a new repair was possible, whereas the 3 other pts required a
valve replacement. All patients but one survived the reoperation. Actuarial
freedom from reoperation was 88% at 7 years.
All 56 patients
with valve repair were reviewed for this study by clinical examination and
echocardiography. All but one were in functional chiss I or II. There was no
MVI in 19, trivial MVI in 17 and moderate MVI in 7. No thromboembolic
complications have been recorded.
This study shows
that complete annulus decalcification and valve repair can be carried out
safely in patients with mitral valve insufficiency and associated extensive
calcification of the annulus, even when the calcification process deeply
involves the myocardium. It also demonstrates that an initially good result
remained stable up to 7 years.
*By invitation
16. POSTINFARCTION VENTRICULAR SEPTAL
RUPTURE: REPAIR BY ENDOCARDIAL PATCH WITH INFARCT EXCLUSION
Tirone E. David, M.D., Laura
Dale, R.N.*, Robert J. Cusimano, M.D.* and Zhao Sun, B.A.*
Toronto, Ontario, Canada
Because the
extent of right ventricular infarction has been identified as an important
determinant in the outcome of pts with postinfarction ventricular septal defect
(VSD), an operation that avoids further damage to the right ventricle was
developed and it has been applied in 43 pts during the past 8 years. The
procedure is performed by opening the left ventricle through the infarcted wall
and by suturing a pericardial patch (fresh autologous or bovine pericardium) to
the endocardium of the left ventricle with a continuous 3-0 polypropylene suture
to exclude the infarcted muscle from the left ventricular cavity. The
ventriculotomy is closed primarily and no infarctectomy is performed.
There were 21
men and 22 women, ages 48 to 84 years, mean 68. Twenty-seven pts were in
cardiogenic shock when operated on and all had an intraaortic balloon pump
inserted preoperatively; 7 of them also required assisted ventilation and 13
were anuric. Doppler echocardiography was used to confirm the diagnosis and
assess left and right ventricular function in all pts. The VSD was anterior in
22 pts and posterior in 21. All pts had coronary angiography. Pts in shock were
operated on as an emergency and most pts who were hemodynamically stable were
operated on within 3 days of diagnosis. In addition to the endocardial pericardial
patch, 29 pts had coronary artery bypass and one pt also had mitral valve
replacement. There were 6 operative deaths (14%); 3 in pts with anterior VSD
and 3 in pts with posterior VSD. Eleven pts required renal dialysis and 15
required assisted ventilation for more than 48 hours. ICU stay (mean ± SD) was
7.8 ± 10.3 days and hospital stay was 20 ± 18 days. Only one pt had a recurrent
VSD but it closed spontaneously within one month. Operative survivors have been
followed from 3 to 95 months, mean of 42. There were 7 late deaths, 4 cardiac.
The actuarial survival at 7 years was 64% ± 8%. The only two factors that were
predictive of mortality were renal failure and left ventricular ejection
fraction <35%, by a stepwise logistic regression analysis. All pts are in
NYHA class I or II. Doppler echocardiography was performed at least once a year
in all survivors and revealed mild impairment of left ventricular function in
18 pts, moderate in 11 and severe in 1. All pts have normal or near normal
right ventricular function.
This new
operative technique is relatively simple and appears to improve the outcome of
pts with postinfarction VSD.
*By invitation
17. AORTIC VALVE REPAIR IN ACUTE TYPE A
DISSECTION: IS IT SOUND?
Ludwig K. von Segesser, M.D.*,
Urs Niederhauser, M.D.*, Marietta Schonbeck, M.D.*, Paul Vogt, M.D.* and Marko
I. Turina, M.D.
Zurich, Switzerland
The last 200 consecutive patients with acute
Stanford type A dissection (157 men [78%], 43 women [22%]) were analyzed in
order to assess the validity of aortic valve repair whenever possible.
Indication for surgery was in most cases based on echocardiographic examination
only in order to reduce the doctors' delay. In the majority of patients
(111/200: 56%), the incompetent aortic valve was resuspended and repaired.
Aortic root replacement with a compositd graft was performed in 66/200 patients
(33%) mainly because of enlarged aortic anulus and sinus portion. Replacement
of the aortic valve and the supracoronary ascending aorta was performed in
23/200 patients (12%) with diseased aortic valve (e.g., bicuspid valve) but
acceptable aortic sinus portion. Follow-up totalized 656 patient years (maximum
14 years). Actuarial analyses as a function of aortic valve type provided the
following probabilities ± errors (95%).
|
|
interval
|
all
|
repaired
|
mechanical
|
biological
|
|
type of valve/patients
|
|
200/200 (100%)
|
111/200(56%)
|
69/200 (34%)
|
20/200(10%)
|
|
survival
|
30 days
|
78.3 ± 2.9
|
72.8 ± 4.3
|
82.7 ± 4.5
|
95.4 ± 4.5
|
|
|
1 year
|
74.9 ± 3 1
|
68.5 ± 4.6
|
82.7 ± 4.5
|
81.1 ± 8.5
|
|
|
5 years
|
67.9 ± 3.6
|
60.8 ± 5.2
|
75 9 ± 5.6
|
76.1 ± 9.3
|
|
|
1 0 years
|
48.5 ± 6.1
|
43.4 ± 8.2
|
64 4 ± 8.9
|
46.7 ± 14.6
|
|
freedom from valve failure
|
30 days
|
100.0 ± 0.0
|
100.0 ± 0.0
|
100.0 ± 0.0
|
100.0 ± 0.0
|
|
|
1 year
|
100.0 ± 0.0
|
100.0 ± 0.0
|
100.0 ± 0.0
|
100.0 ± 0.0
|
|
|
5 years
|
99.1 ± 0.9
|
97.7 ± 2.3
|
100.0 ± 0.0
|
100.0 ± .00
|
|
|
10 years
|
99.1 ± 0.9
|
97.7 ± 2.3
|
100.0 ± 0.0
|
1000 ± 0.0
|
|
freedom from reoperation
|
30 days
|
100.0 ± 0.0
|
I00.0 ± 0.0
|
I00.0 ± 0
|
100.0 ± 0.0
|
|
(same segment)
|
1 year
|
99 3 ± 0.7
|
98.6 ± 1 3
|
100.0 ± 0.0
|
100.0 ± 0.0
|
|
|
5 years
|
97 5 ± 1.5
|
96.7 ± 2.3
|
97.7 ± 2.3
|
