CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 1, January/February 2013
282
AFRICA
541: HYDROGEN SULPHIDE AMELIORATES VOLUME
OVERLOAD-INDUCED VENTRICULAR REMODELLING
BY MATRIX METALLOPROTEINASES (MMP-8, MMP-13)
AND THEIR TISSUE INHIBITOR (TIMP-1) IN RATS
Chaoying Zhang, Xiaohui Li
Children’s Hospital affiliated to Capital Institute of Paediatrics, China
Background:
Chronic heart failure is a common complication of
left-to-right shunt congenital heart disease, and ventricular remodel-
ling is an important pathophysiological basis of volume overload-
induced chronic heart failure. Hydrogen sulphide (H
2
S) is a newly
found gasotransmitter in the cardiovascular system. But the effect
of H
2
S on ventricular remodelling induced by volume overload is
unknown.
Methods:
This study used 30 male Sprague-Dawley rats (120–140
g), which were randomly divided into four groups: shunt group (
n
=
8), sham group (
n
=
8), shunt
+
sodium hydrosulphide (NaHS)
group (
n
=
8), and sham
+
NaHS group (
n
=
6). An animal model
of volume overload was induced by abdominal aorta–inferior vena
cava puncture in the rats. Eight weeks after surgery, left ventricular
matrix metalloproteinase-8 (MMP-8), MMP-13 and tissue inhibitor
of metalloproteinase-1 (TIMP-1) expressions were measured by real-
time PCR, Western blots and immunohistochemistry, respectively.
Results:
Eight weeks after surgery, in the shunt group, MMP-8,
MMP-13 and TIMP-1 mRNA expression and the ratio of MMP-13/
TIMP-1 were significantly increased compared with those in the
sham group (all
p
<
0.05). MMP-13 and TIMP-1 mRNA expression
and the ratio of MMP-13/TIMP-1 were significantly decreased in the
shunt
+
NaHS group compared with those in the shunt group (all
p
<
0.05). Protein expression of MMP-8, MMP-13, TIMP-1, and the
ratios of MMP-8/TIMP-1 and MMP-13/TIMP-1 were significantly
increased in the shunt group compared with those in the sham group
(all
p
<
0.05). Protein expression of MMP-8, MMP-13, TIMP-1 and
the ratio of MMP-8/TIMP-1 were significantly decreased in the shunt
+
NaHS group compared with those in the shunt group (all
p
<
0.05).
Conclusions:
H
2
S might play a protective role in volume overload-
induced ventricular remodelling by regulating protein and mRNA
expression of MMP-8, MMP-13 and TIMP-1.
588: INOTROPIC EFFECTS OF ILOPROST IN THE HYPER-
TROPHIC AND FAILING RIGHT HEART
Sarah Holmboe
1
, Asger Andersen
1
, Mads Dam Vildbrad
1
, Jan Møller
Nielsen
1
, Steffen Ringgaard
2
, Jens Erik Nielsen-Kudsk
1
1
Department of Cardiology, Aarhus University Hospital, Skejby,
Denmark
2
MR Centre, Aarhus University Hospital, Skejby, Denmark
Background:
To investigate whether iloprost has a direct inotropic
effect in the pressure-overloaded hypertrophic and failing right
ventricle (RV).
Methods:
Rats were subjected to pulmonary trunk banding (PTB)
(
n
=
8) or sham operations (
n
=
8). PTB enables evaluation of the
direct effect of iloprost in the right heart, excluding the influence
from pulmonary vasodilation. After the development of RV hyper-
trophy and failure, measurements were made at baseline and after
intravenous administration of placebo, iloprost 10 ng/kg/min (Ilo10)
and iloprost 100 ng/kg/min (Ilo100). Cardiac output, systemic blood
pressure and RV function were evaluated by MRI, echocardiography
and invasive pressure measurements.
Results:
Animals subjected to PTB developed significant RV hyper-
trophy and failure. RV weight/tibia length ratio was elevated and
tricuspid annular plane systolic excursion was markedly decreased
compared to the sham animals. Iloprost caused a decrease in mean
arterial blood pressure (MAP). In both groups of animals, infusion
of Ilo100 induced an increase in stroke volume (placebo vs Ilo100
±
SEM: PTB 0.19
±
0.008 vs 0.21
±
0.01 ml,
p
<
0.01, sham 0.25
±
0.01 vs 0.28
±
0.01 ml,
p
<
0.05) as well as in dP/dt
max
(placebo vs
Ilo100
±
SEM: PTB 4730
±
451 vs 5338
±
605 mmHg/sec,
p
<
0.05,
sham 2218
±
218 vs 2521
±
386 mmHg/sec,
p
<
0.05). Additionally,
an elevation in cardiac output (placebo vs Ilo100
±
SEM: 63.0
±
5
vs 71.4
±
5 ml/min,
p
<
0.001) and RV systolic pressure (placebo
vs Ilo100
±
SEM: PTB 110
±
6 vs 121
±
6 mmHg,
p
<
0.01) were
observed in the PTB group. Infusion of nitroprusside, titrated to
cause the same level of decrease in MAP as iloprost, did not increase
any of the measured parameters.
Conclusion:
Our results suggest that the prostacyclin analogue
iloprost has inotropic properties, directly improving ventricular func-
tion in the hypertrophic and failing as well as in the healthy right
heart.
613: VASCULAR HISTOPATHOLOGICAL REACTION TO
GORE-TEX STRIPS USED FOR PULMONARY ARTERY
BANDING IN AN
IN VIVO
PORCINE EXPERIMENTAL
MODEL
Anke Katharina Furck
1
, Hideki Uemura
1
, Lukáš Nedorost
2
, Imran
Saeed
1
, Jiri Kobr
3
, Zbynekk Tonar
2
, Zdenek Slavik
1
1
Royal Brompton Hospital, Royal Brompton and Harefield NHS
Foundation Trust, Sydney
2
Department of Histology and Embryology, Faculty of Medicine,
Pilsen, Charles University, Prague, Czech Republic
3
Department of Paediatrics, Faculty of Medicine and Faculty Hospital,
Pilsen, Charles University, Prague, Czech Republic
Objective:
Pulmonary artery banding (PAB) is used as a surgical
palliation to reduce excessive pulmonary blood flow caused by
congenital heart defects. Due to the lack of histological studies deal-
ing with tissue remodelling caused by contemporary PAB materials,
our aim was to analyse tissue reaction to the presence of Gore-Tex
strips fixed around the porcine pulmonary artery.
Methods:
Gore-Tex strips were used for PAB in a growing porcine
model. After five weeks, histological samples with PAB (
n
=
5) were
compared to healthy pulmonary arterial segments distal to the PAB or
from sham-operated animal (
n
=
1). Using stereology, we quantified
the density of vasa vasorum and the area fraction of elastin, smooth
muscle actin, macrophages and nervi vasorum within the pulmonary
arterial wall.
Results:
PAB samples had higher amounts of macrophages, lower
amount of nervi vasorum, and a trend towards decreased smooth
muscle content when compared with samples without the PAB strips.
There was no destruction of elastic membranes, no medionecrosis, no
pronounced inflammatory infiltration or foreign body reaction, and
no vasa vasorum deficiency following the PAB. All the histopatho-
logical changes were limited to the banded vascular segment and did
not affect distal parts of the pulmonary artery.
Conclusion:
Our results suggest that Gore-Tex strips used contempo-
rarily for PAB in a clinical setting do not cause as severe histological
damage to the pulmonary arterial wall after five weeks in a growing
porcine PAB model compared with previously published series using
different PAB material.
615: REMOTE ISCHAEMIC PRECONDITIONING MODU-
LATES METABOLISM AND IMPAIRS RECOVERY IN THE
NEONATAL HEART SUBJECTED TO ISCHAEMIA–REPER-
FUSION INJURY
Nicolaj Brejnholt Støttrup
1
, Michael Rahbek Schmidt
1
, Marie
Michelsen
1
, Rune Birkler
2
, Mogens Johannesen
2
, Rajesh K
Kharbanda
3
, Andrew Redington
4
, Hans Erik Bøtker
1
1
Department of Cardiology, Aarhus University Hospital Skejby,
Denmark
2
Department of Forensic Medicine, Aarhus University, Denmark
3
The John Radcliffe Hospital, Oxford NIHR Biomedical Research
Centre, Oxford, UK
4
Division of Cardiology, Hospital for Sick Children, Toronto, ON,
Canada
Background:
Remote ischaemic preconditioning (rIPC) reduces
cardiac injury in older children and adults after cardiac surgery.