CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 1, January/February 2013
280
AFRICA
Background:
Mechanisms for pulmonary hypertension remain
unclear. Sulphur dioxide was recently discovered to be generated
endogenously in vascular tissue and to have important vascular func-
tions; however, the role of the endogenous sulphur dioxide pathway
in the pathogenesis of pulmonary vascular collagen remodelling has
not been defined. The objective of the present study was to explore
the role of sulphur dioxide, a new gaseous signal, in the regulation of
pulmonary vascular collagen remodelling induced by monocrotaline
and its regulatory mechanisms.
Methods:
A rat model of monocrotaline-induced pulmonary hyper-
tension was developed and administered with an L-aspartate-
β
-hydroxamate and sulphur dioxide donor to evaluate the effects
of sulphur dioxide on pulmonary vascular collagen remodelling.
The endogenous sulphur dioxide pathway and collagen metabolism
were examined. Transforming growth factor-
β
1
-stimulated cultured
pulmonary arterial fibroblasts were used to further the study.
Results:
The results showed significant pulmonary hypertension
and pulmonary vascular collagen remodelling in association with
the augmented sulphur dioxide pathway. L-aspartate-
β
-hydroxamate
further increased pulmonary artery pressure and aggravated pulmo-
nary vascular collagen remodelling, accompanied by decreased
sulphur dioxide production. However, sulphur dioxide donor treat-
ment decreased pulmonary artery pressure, attenuated pulmonary
vascular collagen remodelling with inhibited collagen synthesis and
augmented collagen degradation, and decreased transforming growth
factor-
β
1
of the pulmonary arteries. Furthermore, sulphur dioxide
could prevent activation of the p38 signalling pathway as well as
abnormal collagen synthesis in the fibroblasts.
Conclusions:
Up-regulation of the endogenous sulphur dioxide path-
way played a protective role in pulmonary artery collagen remodel-
ling induced by monocrotaline. The mechanisms may involve inhibi-
tion of the transforming growth factor-
β
1
expression and activation of
the p38 signalling pathway.
278: EFFECT OF SULPHUR DIOXIDE ON PULMONARY
ARTERY PRESSURE IN RATS WITH EXPERIMENTAL
ABDOMINALAORTAAND INFERIORVENA CAVA SHUNTING
Cuiping Liu
1
, Yonghong Chen
2
, Xiaohui Li
3
, Yanqiu Zhang
4
, Lulu
Pang
2
, Yan Sun
2
, Junbao Du
2
, Hongfang Jin
2
1
Department of Pediatrics, Tianjin Fifth Central Hospital, Tianjin
300450, PR China
2
Department of Pediatrics, Peking University First Hospital, Beijing
100034, PR China
3
Department of Cardiology, Capital Medical University, Beijing
100020, PR China
4
Department of Paediatrics, Beijing Shunyi Hospital, Beijing 101300,
PR China
Objective:
To explore the effect of sulphur dioxide on the pulmonary
artery pressure of rats with abdominal aorta and inferior vena cava
shunting.
Methods:
Twenty-five male Sprague Dawley rats were randomly
divided into a shunting group, a shunting with sulphur dioxide group,
and a control group. Abdominal aorta and inferior vena cava shunting
was produced in rats in the shunting group and in the shunting with
sulphur dioxide group. After an eight-week shunting, the pulmonary
artery pressure of each rat was evaluated using the right cardiac cath-
eterisation procedure.
Results:
Compared with the control group, the mean, systolic and
diastolic pulmonary artery pressures were raised in the shunt rats
(72.88, 58.33 and 43.35%, respectively). Compared with the shunting
group, the systolic pulmonary artery pressure of rats in the shunting
with sulphur dioxide group decreased by 22.12% (
p
<
0.05), the
mean pulmonary artery pressure decreased by 20.63% (
p
<
0.05) but
the diastolic pulmonary artery pressure did not change (
p
<
0.05).
Conclusion:
Sulphur dioxide decreased the mean and systolic
pulmonary artery pressures of rats with abdominal aorta and inferior
vena cava shunting.
291: ISCHAEMIA AND ISCHAEMIC PRECONDITIONING
IN THE HYPERTROPHIC AND FAILING RIGHT HEART
Asger Andersen, Jonas A Povlsen, Hans Erik Bøtker, Jens Erik
Nielsen-Kudsk
Department of Cardiology Research, Clinical Institute, Aarhus
University Hospital, Skejby, Denmark
Aim:
To investigate the response to ischaemia and ischaemic precon-
ditioning in the hypertrophic and failing right heart.
Methods:
Male Wistar rats (
n
=
74) were subjected to a sham opera-
tion (
n
=
24), moderate pulmonary trunk banding (mPTB,
n
=
24)
or severe pulmonary trunk banding (sPTB,
n
=
26). Four weeks
after the operation, the right ventricle (RV) weight and function was
evaluated. Hearts were quick-frozen (
n
=
28) or isolated and perfused
in Langendorff apparatus (
n
=
46) with Krebs-Henseleit buffer. The
perfused hearts were randomised to IPC (2
×
5 min of global ischae-
mia) or no preceding ischaemia (CON), followed by 40 minutes of
global ischaemia and 120 minutes of reperfusion. Measurement of
the infarct size/area-at-risk (IS/AAR) ratio and post-ischaemic RV
function was used to evaluate the effect of IPC on the right ventricle.
The quick-frozen hearts were used to evaluate key components of the
GPCR/NPR-AKT-eNOS-PKG and RISK pathways.
Results
: The mPTB procedure caused compensated RV hypertro-
phy and the sPTB procedure caused RV hypertrophy with failure.
Hypertrophy of the RV caused an increase in infarct size in hearts
from mPTB and sPTB animals compared to sham rats (IS/AAR:
66.5
±
3.4; 59.3
±
2.4 vs 35.6
±
2.9% respectively,
p
<
0.0001).
Cardioprotection by IPC was possible in sham and mPTB hearts,
measured by a decrease in IS/AAR and improved haemodynamic
recovery of RV contractile function. The mPTB procedure did not
cause an increase in RV cGMP. In sPTB hearts with hypertrophy and
failure, IPC did not improve IS/AAR or haemodynamic recovery and
an increase in RV cGMP was observed.
Conclusion:
Right ventricular hypertrophy increased infarct size, and
when failure was present, abolished cardioprotection by ischaemic
preconditioning in the right ventricular myocardium of the rat. The
abolition of cardioprotecion was followed by an increase in myocyte
cGMP. It will be investigated whether there was a causal connection.
337: MUTATIONS IN CALMODULIN AND VENTRICU-
LAR TACHYCARDIA, SYNCOPE AND SUDDEN CARDIAC
DEATH
Inger Fosdal Tevebring
1
, Goran Wettrell
2
, Mette Nyegaard
3
, Michael
T Overgaard
4
, Mads Toft Sondergaard
4
, Marta Vranas
3
, Elijah R
Behr
5
, Lasse L Hildebrandt
4
, Jacob Lund
4
, Paula L Hedley
6
1
Department of Paediatrics, Visby Hospital, Gotland, Sweden
2
Division of Paediatric Cardiology, Lund University Hospital, Lund,
Sweden
3
Department of Biomedicine, Aarhus University, Aarhus, Denmark
4
Department of Biotechnology, Chemical and Environmental
Engineering, Aalborg University, Denmark
5
Division of Cardiac and Vascular Sciences, St George’s University
of London, UK
6
Department of Clinical Biochemistry and Immunology, SSI,
Copenhagen, Denmark
Primary arrhythmias such as long QT syndrome (LQTS) and
catecholaminergic polymorphic ventricular tachycardia (CPVT) may
cause syncope and sudden cardiac death. CPVT might be suspected
with a history of exercise/emotion-related syncope, sudden cardiac
death, normal QT
c
on ECG and normal structure of the heart.
Methods:
A genome-wide linkage analysis of a large four-generation
Swedish family with CPVT-like disease but without mutations in the
cardiac ryanodine receptor gene (RYR2) was performed. A candidate
gene involving calcium homeostasis was analysed for mutations
using sequencing. The functional consequences of the identified
mutation were determined using a calcium-binding assay.
Results:
A novel locus for a severe dominantly inherited CPVT-
like disease was identified on chromosome 14q31-32. Sequencing
