CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 1, January/February 2013
AFRICA
279
either MSCs or primary mouse lung fibroblasts (MLFs), and placed
in room air for two to four weeks. Histological analysis of the lungs
harvested at four weeks of age was performed to determine the
degree of alveolar injury, blood vessel number and vascular remodel-
ling. At six weeks of age, pulmonary artery pressure (PA acceleration
time) and right ventricular hypertrophy (RVH; RV wall thickness)
were assessed by echocardiography, and pulmonary function tests
were conducted.
Results:
When compared to MLF-CM, a single dose of MSC-CM-
treatment (1) reversed the hyperoxia-induced parenchymal fibrosis
and peripheral PA devascularisation (pruning), (2) partially reversed
alveolar injury, (3) normalised lung function (airway resistance,
dynamic lung compliance), (4) fully reversed the moderate PH and
RVH, and (5) attenuated peripheral PA muscularisation associated
with hyperoxia-induced BPD. A microRNA expression analysis on the
hyperoxia-induced BPD lungs
±
MSC-CM intervention is underway.
Conclusion:
To the best of our knowledge this is the first evidence
that reversal of key features of hyperoxia-induced BPD and its long-
term adverse effects on lung function can be achieved by a single
intravenous dose of MSC-CM
in vivo
, thereby pointing to a new
therapeutic intervention for chronic lung diseases, including pulmo-
nary hypertensive vascular disease.
210: REMOTE ISCHAEMIC PRECONDITIONING WITH,
BUT NOT WITHOUT METABOLIC SUPPORT PROTECTS
AGAINST ISCHAEMIA–REPERFUSION INJURY IN THE
NEWBORN PIGLET IN VIVO
Michael Rahbek Schmidt
1
, Nicolaj Brejnholt Stottrup
1
, Marie Mide
Michelsen
1
, Rune Birkler
2
, Mogens Johannesen
2
, Rajesh Kharbanda
3
,
Andrew Redington
4
, Hans Erik Bøtker
5
1
Department of Cardiology, Aarhus University Hospital Skejby,
Denmark
2
Section for Toxicology and Drug Analysis, Department of Forensic
Medicine, Aarh
3
The John Radcliffe Hospital, Oxford NIHR Biomedical Research
Centre, Oxford, UK
4
Division of Cardiology, Hospital for Sick Children, Toronto, ON,
Canada
5
Department of Cardiology, Aarhus University Hospital, Skejby,
Denmark
Introduction:
While remote ischaemic preconditioning (rIPC)
protects the mature heart against ischemia–reperfusion (IR) injury,
the effect of rIPC on the neonatal heart is controversial. The neona-
tal heart relies almost solely on carbohydrate metabolism, which is
modified by rIPC in the mature heart. Glucose–insulin (GI) infu-
sion provides myocardial substrate supplementation, which may
compensate for the adverse metabolic effects induced by rIPC in the
immature heart.
Hypothesis:
rIPC combined with GI improves cardiac function and
reduces infarct size compared to control or rIPC alone after IR injury
in neonatal piglets
in vivo
.
Methods:
Thirty-two newborn (one to four days old) piglets were
randomised into four groups: control, rIPC, GI and GI
+
rIPC. The
GI and GI
+
rIPC groups received insulin in 20% glucose at a rate
corresponding to 100 mU/kg/h continuously from 40 minutes prior
to ischaemia. The rIPC and GI
+
rIPC groups underwent four cycles of
five-minute limb ischaemia followed by five minutes of reperfusion.
Myocardial IR was induced by 40 minutes of occlusion of the left
anterior descending artery followed by two hours of reperfusion. Left
ventricular pressure was measured using 3-F Millar microtip cathe-
ters. Interstitial lactate was measured using microdialysis, and infarct
size was measured using triphenyltetrazolium chloride staining.
Results:
Systolic recovery (dP/dt
max
as % of baseline) after two hours’
reperfusion was improved in GI
+
rIPC (84.7
±
5.3%) compared to the
controls (71.2
±
4.9%,
p
<
0.05) and rIPC (33.9
±
12.9%,
p
<
0.01)
but was not different from the GI group (82.9
±
8.1%, ns). Lactate
levels (% of baseline) were lower in the GI
+
rIPC (85.5
±
4.9%)
compared to controls (125.1
±
9.1%,
p
<
0.01) and rIPC group (233.9
±
31.1%,
p
<
0.01). Infarct size relative to area at risk was 12.7
±
1.1% in GI
+
rIPC compared to 16.4
±
1.5% controls (
p
=
0.06), 18.1
±
0.8% in rIPC (
p
<
0.01) and 24.1
±
2.1% in the GI group.
Conclusion:
rIPC
+
GI, but neither rIPC nor GI alone protected the
neonatal porcine heart against IR injury
in vivo
. rIPC alone appears
to have had detrimental metabolic and functional effects that were
compensated for by simultaneous metabolic support with GI infusion.
251: IRON HOMEOSTASIS PLAYED A CRITICAL ROLE IN
THE PROCESS OF CARDIOMYOCYTE HYPERTROPHY
DURING LEFT VENTRICULAR RETRAINING FOR CHIL-
DRENWITH TRANSPOSITION OF THE GREAT ARTERIES
Hao Zhang
1,2
, Yihe Wu
1
, Shoujun Li
2
, Shengshou Hu
1,2
1
National Centre for Cardiovascular Diseases, Cardiovascular
Institute and Fuwai Hospital, Chinese Academy of Medical Sciences
and Peking Union Medical College, Beijing, China
2
Center for Paediatric Cardiac Surgery, Cardiovascular Institute and
Fuwai Hospital, Chinese Academy of Medical Sciences and Peking
Union Medical College, Beijing, China
Background:
The left ventricle (LV) regresses after the neonatal
period in patients with transposition of the great arteries (TGA) with
an intact ventricular septum (IVS) or restrictive ventricular septal
defect (VSD). Pulmonary artery banding (PAB) can induce cardio-
myocyte hypertrophy for the subsequent arterial switch operation.
We screened the altered plasma proteins after PAB and explored the
implications for LV retraining.
Methods:
Eight late-referral children with TGA/IVS or small VSD
were enrolled in part I of the study. The plasma was collected 30
minutes before and 48 hours after PAB. Differential gel electropho-
resis (DIGE) proteomics was used to identify
the altered proteins.
The significantly changed proteins were then confirmed by ELISA.
In part II of the study, children with TGA (
n
=
16) undergoing PAB
and matched children undergoing open-chest surgery without cardio-
pulmonary bypass (
n
=
12) were enrolled and the changed level of
the chosen proteins was measured. In part III of the study, cell size
and mRNA expression of the biomarkers for cardiac hypertrophy
were evaluated in a neonatal cardiomyocyte culture model with the
associated protein.
Results:
Proteomic analysis revealed significant change in 25
proteins. Furthermore, ELISA analysis showed three differential
proteins, including ceruloplasmin (CP), transferrin (TF) related to
iron ion homeostasis, and parvalbumin (PVALB) related to heart
development, were regulated 1.37-, 1.33-, 1.38-fold, respectively.
These changes were confirmed in part II of the study to exclude the
involved inflammatory response during open-chest surgery. The
in
vitro
study showed that after 48 hours’ incubation with TF, the size of
cardiomyocytes increased 1.94 times. Meanwhile, the expression of
natriuretic peptide precursor A and B and PVALB was significantly
enhanced.
Conclusions:
Augmented levels of CP and TF indicated iron homeo-
stasis played a critical role in the process of immature cardiomyocyte
hypertrophy during LV retraining. TF could directly promote cardio-
myocyte hypertrophy and hold therapeutic/prognostic potential in
clinical practice.
272: ENDOGENOUS SULPHUR DIOXIDE REGULATES
MONOCROTALINE-INDUCED PULMONARY VASCULAR
COLLAGEN REMODELLING IN RATS
Die Liu
1
, Chen Liang
1
, Todd Ochs
2
, Stella Chen
3
, Shuxu Du
1
, Xia
Zhao
1
, Chaoshu Tang
4,5
, Hongfang Jin
1
, Junbao Du
1,4
1
Department of Paediatrics, Peking University First Hospital, Beijing
100034, PR China
2
Northwestern University, Chicago, USA
3
Department of Biochemistry and Cellular Biology, University of
California, San Diego La Jolla, CA, USA
4
Institute of Cardiovascular Diseases, Peking University First
Hospital, Beijing 100034, PR China
