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Metallothionein is involved in reverse remodelling after prolonged left ventricular assist device support
The Journal of Heart and Lung Transplantation Volume 18, Number 1
Abstracts
pite both thd contact with a textured surface and device&ated polsatile flow ynamics, platelet and inflammatory pathway activation do not OCCUTdoting chronic Doring the period of soppon there is incmesed thrombin generation with We conclude that these markers reflect the bi-patibility of &vice and suggest that permanent mechanical support could safely become a
57
min (P=ll 03) ( ‘rurclu.~rons: In LVAD patients. subendccardial left ventricular MT c\prcssron is associated inverseI? with duration of LVAD support and abuIlt\ IO exercise These data support a potential role of MT in endstage cardrom!opath! and rcversc remodelling after longterm LVAD support.
90 MG POSTPONES ALLOIMMUNIZATION IN LVAD AND kRnnCIAL HEART RECIPIENTS S. H. McKellar, J.D. Marks , D.G. Renlond*, J.W. Long, LDS Hospital, Salt L&c City, Utah, U.T.A.H. Card& Transplant Program Introduction: Left Ventricolar As& Devices (LVAD) and Artificial Hearts (AH) are freqoently used to bridge heart failure pi&s to transplant. Ooc complication e~riencedamongLVADandAHpatientsisalloimmunizationwithHLA-Ant~~ detectedwithWnelReactive Antlbody(?RA) scxens. BlcvatedPRAcanpmlongand may complicate traosplantation. Intravenous Inmmnoglobolin (IV@ has been administered to alloimmonized patients to redoce antitady levels. We have hypothesized that prophylactic administration of IVIg may prevent or delay alloimmonization. This shtdy tests this hypothesis by evaluating the efficacy of administering Mg to LVAD and AH recipients, following device implantation and ttamhsion. Metboda: Twenty NYHA Class IV patients with pm-implant F’RA of 0% received either a TCI HeartMate LVAD (n=16) or a CardioWest AH (n=4). Seven of the 20 patients (Group I) received IQ; a dose of 10 gms q 24 boors for four doses following LVAD implantation and associated transfusions. Group II did not receive Mg. All patients received cellular blood pmdocts filtered to remove leokocytes to prevent alloimmmtization. PRA screens were then cmtdu&d monthly throughout LVAD or AH duration. Alloimmonization was &ii& as having a mean post-implant FRA of >lO%.
INFLAMMATORY DYSFUNCTION
CYTOKINES PLAY
FOLLOWING
AND HEF’ATlC
A ROLE
IMF’L4NTATION
SINUSOID
IN HYPERBIIJRUBINEML4
ENDOTHELIAL IN PATIENTS
OF AN LVAS
M. Nishimura, S. Ohtake, Y. Sawa. N. Fukushima, T. Yamaguchi, H. Matsuda, Osaka University,
Suita. Osaka, Japan
To clarify the mechanism of hyperbilimbinemia ventricular
assist system (LVAS),
sinusoid endothelial inflammatory
function,
cytokines
after the implantation of a let?
the change in hepatocxllular
the blood flow
before and after LVAS
of portal
bilimbin @ST)],
~.Bil~ intedeukin
traesaminase F-6.
[&mine transaminase
IL-g),
and hyalumnic
h*patic
vein and the level of
implantation
consecutive patients ucdenuent the placement of LVAS,
function,
were evaluated. Nine
and serum levels of total
(ALQ
aspartate traasaminase
acid (HA),
an indicator of h+ic
sinusoidal eodothelial function, wex measured before and after LVAS implantation. llx blood flow of portal vein (PV flow) was also evaluated by Doppler ultrasound. T.BiI of all patients increased significantly
in the first Post operative week @<0.05 vs. preop).
lo six patients, the elevated T.Bil rrtumed to preoperative
levels by the 14th post-
operative day, but in the other three patients who died of multiple organ failure, the level P-sell&&d mytoPRA>lo%
of T.Bil increased to 25 ?5 mg/dl. Levels of HA and IL-8 had good Positive correlation 91*33
50+13
p-0.05'
I
with the level of T.Bil (HA: ~0.62,
Coacluslans: The time to peak PRA of >lO% was significantly longer in those patients who tived IVIG. None of the patients who received IVIG developed a mean PRA of >lO% compared to 23K of patients who did not. IVlg appears to be associated with a longer time from device implantation to PRA >lO%. Additional studies are required to detemxine if continuous IVIg therapy can prevent alloimmonization in LVAD and Artiicial Heart recipients.
89
METALLOTHIONEIN IS INVOLVED IN REVEliSE REMODELLING AFTER PROLONGED LEFT VENTRKULAR ASSIST DEVICE SUPPORT H.A Babel’. T D T Tjan’. C August’. B Asfoui. G. Plenz’, C. Schmid2, K.W. Schnlrd’. D. Hammel’. M. Weyand’. H.H. Scheld’, M.C. De&. l&tote of Palholog! Department of Cardiotboracic Surgery’. Institute of Arteriosclerosis Rcscarch (Dcpt of Cell Blolog? and Ultrastructural Research)‘. Muenster Uni\crs# Hospital. German? Durmg left ventricular assist device (LVAD) support revem rcntodcllmg lakes place. The role of metallothionein (MT), a highly conserved n~olcculc inducible by promflammatoq cytokines with a potential role in ox!gca free radical scavenging in ischemic myocardium has not been examined tn this conlcu. .\/erho& Seventeen patients with end-stage heart failure (9 dilarcd cardiom!opatb>. 6 ischemic heart disease. 1 myocarditis. 1 congenital ham discasc. mean age 41 f 10 y. mean duration of support 139 d f 92. range 14 - TO9 d) \\ho undentent successful LVAD implantation (15 x Novacor, 2 x TCI Hcartmatc) as a bridge to transplantation were studied. Formalin-fixed, paraftin-cmbcdded left ventricular free wall myocardial specimens were hancacd at LVAD implantation @rrr.l: ID) and transplantation @tLl:dD) aud anal! /cd with regard to MT expression by immunohistochemistry (~nonoclo~~al aorrbod! E9. Dako. scmrquantitative score) and myocyte diameters (MYOD) b? morphomet~ witb the aid of an image analyzer. Both parameters ucrc anal! dcd n Ith respect to subendocardial. midmyocardial and sobepicardial sections He\ulr.\- MT expression uas detected in cardiomyocytes. small vessels, and fibroblasts. Compared to pm/J: ID. MT expression and h4YOD were s~g~ufica~~tl! loner p~~.eLl: II) (p=O.O06 and P=O.O3. rcsp). This difference was mainI! c\plaincd b! reduction in subendocardial MT and MYOD (p=O.OOS and 1) 0.5. rcsp) Funhcrmore. MT expression posrLl;4D was lower in patients with lotlgcr LVAD support duration (P=O.OOl) and ability to exercise on the 75 watt Ic\cl \\11h a newI! developed LVAD pump rate challenge stress protocol for 15
pcO.05; a-8:
negative correlation with the level of HA (r=l.O, that inflammatory
cytokines
r=O.75, p~O.0001) and PV flow had p
causes hepatic endothelial dysfonction
decrease in hepatic blood flow and these mechanisms hepatic failure in patients following
91
and subseaent
may play a significant
role in
implantation of an LVAS.
EDUCATION AND THE TRANSPLANTED CHILD J. Wray. R. Radley-Smith. M. Yacoob. Harefield Hospital. Harefield U.K
Middlesex.
With the increasing numbers of children undergoing successful heart and heart-lung transplantation. and the improvements in duration of sunival. issues such as education and the impact of transplantation on academic and behaviooral parameters now need to be addressed Seventy-five children and adolescents were assessed with regard to their academic attainments and behaviour at school at regular intervals after heart (n=46) or heart-lung (0=29) transplantation and comparisons were made with a group of healthy children. Cognitive ability and academic attainments were assessed with the British Abili& Scales. The prevalence of behaviour pmbleors was assessed with the Rotter B scales. completed by the teachers, and parents were additionally asked to report their concerns about academic and adjustment problems at school. The average length of absence from school after transplantation was 5 months (range: 2-23 months) and 9 (12%) of the children attended special school. with the remainder attending normal school. Cognitive ability and performance on academic attainments were within the normal range and did not change significantly as a function of time since transplant. However. performance was at a significantly lower level than that of the healthy children. Whilst the prevalence of behaviour problems was only 7% at 6 months post-transplant. at 3 years it had increased to 28% and at 5 years it was still 22%, which is higher than that found in the healthy group (7%). Parental reporting of academic and adjustment problems also peaked at 3 years post-transplant (38% and 24% respectively). It is concluded that a significant number of children who have undergone successfol heart or heart-lung transplantation experience difficolties at school and that, contrary to expectations, educational problems are more prevalent in the medium term. rather than in the short-term. after transplantation.
Abstracts
pite both thd contact with a textured surface and device&ated polsatile flow ynamics, platelet and inflammatory pathway activation do not OCCUTdoting chronic Doring the period of soppon there is incmesed thrombin generation with We conclude that these markers reflect the bi-patibility of &vice and suggest that permanent mechanical support could safely become a
57
min (P=ll 03) ( ‘rurclu.~rons: In LVAD patients. subendccardial left ventricular MT c\prcssron is associated inverseI? with duration of LVAD support and abuIlt\ IO exercise These data support a potential role of MT in endstage cardrom!opath! and rcversc remodelling after longterm LVAD support.
90 MG POSTPONES ALLOIMMUNIZATION IN LVAD AND kRnnCIAL HEART RECIPIENTS S. H. McKellar, J.D. Marks , D.G. Renlond*, J.W. Long, LDS Hospital, Salt L&c City, Utah, U.T.A.H. Card& Transplant Program Introduction: Left Ventricolar As& Devices (LVAD) and Artificial Hearts (AH) are freqoently used to bridge heart failure pi&s to transplant. Ooc complication e~riencedamongLVADandAHpatientsisalloimmunizationwithHLA-Ant~~ detectedwithWnelReactive Antlbody(?RA) scxens. BlcvatedPRAcanpmlongand may complicate traosplantation. Intravenous Inmmnoglobolin (IV@ has been administered to alloimmonized patients to redoce antitady levels. We have hypothesized that prophylactic administration of IVIg may prevent or delay alloimmonization. This shtdy tests this hypothesis by evaluating the efficacy of administering Mg to LVAD and AH recipients, following device implantation and ttamhsion. Metboda: Twenty NYHA Class IV patients with pm-implant F’RA of 0% received either a TCI HeartMate LVAD (n=16) or a CardioWest AH (n=4). Seven of the 20 patients (Group I) received IQ; a dose of 10 gms q 24 boors for four doses following LVAD implantation and associated transfusions. Group II did not receive Mg. All patients received cellular blood pmdocts filtered to remove leokocytes to prevent alloimmmtization. PRA screens were then cmtdu&d monthly throughout LVAD or AH duration. Alloimmonization was &ii& as having a mean post-implant FRA of >lO%.
INFLAMMATORY DYSFUNCTION
CYTOKINES PLAY
FOLLOWING
AND HEF’ATlC
A ROLE
IMF’L4NTATION
SINUSOID
IN HYPERBIIJRUBINEML4
ENDOTHELIAL IN PATIENTS
OF AN LVAS
M. Nishimura, S. Ohtake, Y. Sawa. N. Fukushima, T. Yamaguchi, H. Matsuda, Osaka University,
Suita. Osaka, Japan
To clarify the mechanism of hyperbilimbinemia ventricular
assist system (LVAS),
sinusoid endothelial inflammatory
function,
cytokines
after the implantation of a let?
the change in hepatocxllular
the blood flow
before and after LVAS
of portal
bilimbin @ST)],
~.Bil~ intedeukin
traesaminase F-6.
[&mine transaminase
IL-g),
and hyalumnic
h*patic
vein and the level of
implantation
consecutive patients ucdenuent the placement of LVAS,
function,
were evaluated. Nine
and serum levels of total
(ALQ
aspartate traasaminase
acid (HA),
an indicator of h+ic
sinusoidal eodothelial function, wex measured before and after LVAS implantation. llx blood flow of portal vein (PV flow) was also evaluated by Doppler ultrasound. T.BiI of all patients increased significantly
in the first Post operative week @<0.05 vs. preop).
lo six patients, the elevated T.Bil rrtumed to preoperative
levels by the 14th post-
operative day, but in the other three patients who died of multiple organ failure, the level P-sell&&d mytoPRA>lo%
of T.Bil increased to 25 ?5 mg/dl. Levels of HA and IL-8 had good Positive correlation 91*33
50+13
p-0.05'
I
with the level of T.Bil (HA: ~0.62,
Coacluslans: The time to peak PRA of >lO% was significantly longer in those patients who tived IVIG. None of the patients who received IVIG developed a mean PRA of >lO% compared to 23K of patients who did not. IVlg appears to be associated with a longer time from device implantation to PRA >lO%. Additional studies are required to detemxine if continuous IVIg therapy can prevent alloimmonization in LVAD and Artiicial Heart recipients.
89
METALLOTHIONEIN IS INVOLVED IN REVEliSE REMODELLING AFTER PROLONGED LEFT VENTRKULAR ASSIST DEVICE SUPPORT H.A Babel’. T D T Tjan’. C August’. B Asfoui. G. Plenz’, C. Schmid2, K.W. Schnlrd’. D. Hammel’. M. Weyand’. H.H. Scheld’, M.C. De&. l&tote of Palholog! Department of Cardiotboracic Surgery’. Institute of Arteriosclerosis Rcscarch (Dcpt of Cell Blolog? and Ultrastructural Research)‘. Muenster Uni\crs# Hospital. German? Durmg left ventricular assist device (LVAD) support revem rcntodcllmg lakes place. The role of metallothionein (MT), a highly conserved n~olcculc inducible by promflammatoq cytokines with a potential role in ox!gca free radical scavenging in ischemic myocardium has not been examined tn this conlcu. .\/erho& Seventeen patients with end-stage heart failure (9 dilarcd cardiom!opatb>. 6 ischemic heart disease. 1 myocarditis. 1 congenital ham discasc. mean age 41 f 10 y. mean duration of support 139 d f 92. range 14 - TO9 d) \\ho undentent successful LVAD implantation (15 x Novacor, 2 x TCI Hcartmatc) as a bridge to transplantation were studied. Formalin-fixed, paraftin-cmbcdded left ventricular free wall myocardial specimens were hancacd at LVAD implantation @rrr.l: ID) and transplantation @tLl:dD) aud anal! /cd with regard to MT expression by immunohistochemistry (~nonoclo~~al aorrbod! E9. Dako. scmrquantitative score) and myocyte diameters (MYOD) b? morphomet~ witb the aid of an image analyzer. Both parameters ucrc anal! dcd n Ith respect to subendocardial. midmyocardial and sobepicardial sections He\ulr.\- MT expression uas detected in cardiomyocytes. small vessels, and fibroblasts. Compared to pm/J: ID. MT expression and h4YOD were s~g~ufica~~tl! loner p~~.eLl: II) (p=O.O06 and P=O.O3. rcsp). This difference was mainI! c\plaincd b! reduction in subendocardial MT and MYOD (p=O.OOS and 1) 0.5. rcsp) Funhcrmore. MT expression posrLl;4D was lower in patients with lotlgcr LVAD support duration (P=O.OOl) and ability to exercise on the 75 watt Ic\cl \\11h a newI! developed LVAD pump rate challenge stress protocol for 15
pcO.05; a-8:
negative correlation with the level of HA (r=l.O, that inflammatory
cytokines
r=O.75, p~O.0001) and PV flow had p
causes hepatic endothelial dysfonction
decrease in hepatic blood flow and these mechanisms hepatic failure in patients following
91
and subseaent
may play a significant
role in
implantation of an LVAS.
EDUCATION AND THE TRANSPLANTED CHILD J. Wray. R. Radley-Smith. M. Yacoob. Harefield Hospital. Harefield U.K
Middlesex.
With the increasing numbers of children undergoing successful heart and heart-lung transplantation. and the improvements in duration of sunival. issues such as education and the impact of transplantation on academic and behaviooral parameters now need to be addressed Seventy-five children and adolescents were assessed with regard to their academic attainments and behaviour at school at regular intervals after heart (n=46) or heart-lung (0=29) transplantation and comparisons were made with a group of healthy children. Cognitive ability and academic attainments were assessed with the British Abili& Scales. The prevalence of behaviour pmbleors was assessed with the Rotter B scales. completed by the teachers, and parents were additionally asked to report their concerns about academic and adjustment problems at school. The average length of absence from school after transplantation was 5 months (range: 2-23 months) and 9 (12%) of the children attended special school. with the remainder attending normal school. Cognitive ability and performance on academic attainments were within the normal range and did not change significantly as a function of time since transplant. However. performance was at a significantly lower level than that of the healthy children. Whilst the prevalence of behaviour problems was only 7% at 6 months post-transplant. at 3 years it had increased to 28% and at 5 years it was still 22%, which is higher than that found in the healthy group (7%). Parental reporting of academic and adjustment problems also peaked at 3 years post-transplant (38% and 24% respectively). It is concluded that a significant number of children who have undergone successfol heart or heart-lung transplantation experience difficolties at school and that, contrary to expectations, educational problems are more prevalent in the medium term. rather than in the short-term. after transplantation.