CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 1, January/February 2013
278
AFRICA
BASIC SCIENCES
(2) The non-MPS male fibres showed significantly higher force
values compared to males with MPS (
p
=
0.0002). (3) Female fibres
did not show significant differences in contractile behaviour between
MPS and non-MPS fibres.
Conclusion:
Our data showed a statistically significantly different
contractile behaviour of male and female fibres with and without
MPS. A lowered calcium sensitivity, which leads to a deficiency in
the Frank-Starling mechanism might be the physiological correlation
for this observation and may be a clinical indication for optimised
pre-operative treatment of these patients.
164: IMPACT OF GENDER ON CONTRACTILE BEHAVIOUR
OF SKINNED PAPILLARY MUSCLE OF FEMALE AND
MALE PATIENTS WITH MUCOPOLYSACCHARIDOSIS
Constanze Bening, Helge Weiler, Ahmad Abugameh, Christian-
Friedrich Vahl
Department of Cardiothoracic and Vascular Surgery, University
Mainz, Germany
Background:
Mucopolysaccharidoses (MPS) are a group of meta-
bolic disorders caused by the absence of lysosomal enzymes, which
cause dermatan and heparan sulfate to accumulate in the tissue. There
is a lack of information regarding the impact of gender on these lyso-
somal storage diseases.
Methods:
We examined right atrial tissue of three patients with MPS
I or II (
n
=
9, three preparations per patient) and significant stenosis
of the mitral (
Δ
p
mean
=
17
±
11.5 mmHg) and aortic valves (
Δ
p
mean
=
40
±
21 mmHg) and undergoing valve replacement. Human
tissue was obtained from the right atrium before implementation of
ECC, and it was prepared and stimulated with a stepwise increase in
calcium-containing solution. The results were recorded.
Results:
All fibres developed the greatest force (mean: 1.71
±
0.75
mN) at the highest calcium concentration (pCa 4.5). Male MPS
fibres developed statistically significantly less force then female
fibres (
p
=
0.016). The contractile behaviour of the female fibres
differed significant from the male fibres (
p
=
0.02 for MPS male 1,
and
p
=
0.03 for MPS male 2). Calcium sensitivity, i.e. pCa²
++
50
was
also statistical significant different between male and female fibres
(pCa 5.5, female vs male fibres,
p
=
0.01).
Conclusion:
The data showed differences in contractile performance
in these fibres and imply a different sensitivity in male and female
MPS patients. We feel it is justified to report these limited results
because this is an extremely rare kind of disease. It may help to
consider specific peri-operative treatment for patients with MPS.
198: MESENCHYMAL STEM CELL-MEDIATED REVERSAL
OF BRONCHOPULMONARY DYSPLASIA AND ASSOCI-
ATED PULMONARY HYPERTENSION
Georg Hansmann
1,2
, Angeles Fernandez-Gonzalez
2
, Muhammad
Aslam
2
, Sally H. Vitali
2
, Thomas Martin
2
, S Alex Mitsialis
2
, Stella
Kourembanas
2
1
Hannover Medical School, Germany
2
Children’s Hospital Boston, Harvard Medical School, Boston,
Massachusetts, USA
Clinical trials have failed to demonstrate an effective preventative or
therapeutic strategy for bronchopulmonary dysplasia (BPD), a multi-
factorial chronic lung disease in preterm infants, which is frequently
complicated by pulmonary hypertension (PH). Mesenchymal stem
cells (MSCs) and their secreted components have been shown to
prevent BPD and pulmonary fibrosis in rodent models. We hypoth-
esised that treatment with conditioned media (CM) from cultured
mouse bone marrow-derived MSCs could reverse hyperoxia-induced
BPD and PH.
Methods:
Newborn mice were exposed to hyperoxia (FiO2
=
0.75)
for two weeks, then treated with one intravenous dose of CM from
83: FOETAL AND NEONATAL DUCTUS ARTERIOSUS IS
REGULATEDWITHATP-SENSITIVE POTASSIUM CHANNEL
Kazuo Momma, Emiko Hayama, Toshio Nakanishi
Department of Paediatric Cardiology, Tokyo Women’s Medical
University, Tokyo, Japan
Background:
The foetal patency and neonatal closure of the
ductus arteriosus (DA) is regulated with oxygen and prostaglandins.
The proposed oxygen sensors of foetal and neonatal DA include
P450-endothelin and the Kv channel. We hypothesised that the
ATP-sensitive potassium channel (K
ATP
channel) is another oxygen
sensor.
Methods:
Foetal and neonatal DA were studied in Wistar rats
using sulfonylurea drugs, including tolbutamide, chlorpropamide,
gliclazide, glimepiride and glibenclamide (K
ATP
channel inhibitors),
diazoxide and pinacidil (K
ATP
channel openers: KCOs), and rapid
whole-body freezing.
Results
: Tolbutamide, chlorpropamide and gliclazide easily passed
across the placenta, and dose-dependently constricted foetal DA
following orogastric administration to near-term pregnant rats.
The foetal DA constricted 30% with clinical doses of sulfonyl-
urea drugs, and closed completely with larger doses. Glimepiride
and glibenclamide passed across the placenta minimally, and only
mildly constricted the foetal DA after maternal administration, but
constricted and closed the foetal DA dose-dependently with direct
foetal injection. Foetal DA closure was associated with hydrops and
foetal death. Diazoxide and pinacidil delayed DA closure following
neonatal injection immediately post-natally, and dilated the closed
the DA with injection 30 minutes post-natally.
Conclusions
: All tested sulfonylurea drugs constricted foetal DA
dose-dependently and with complete closure at large doses. KCOs
dilated the neonatal DA. These results indicate physiological regula-
tion of foetal and neonatal DA with K
ATP
channels. This study has
several clinical implications. Sulfonylurea-associated foetal death
was first reported in South Africa 50 years ago. The mechanism of
death remained unclear prior to this study. Sulfonylureas may be
useful for closing patent DA in premature neonates. The recently
reported reopening of neonatal DA associated with the use of
diazoxide for hyperinsulinaemic hypoglycaemia has been proved
experimentally. The DA-dilating effect of KCO drugs may be useful
as a bridge to surgery in neonatal DA-dependent congenital heart
diseases.
163: COMPARISON OF CONTRACTILE PERFORMANCE
OF PATIENTSWITHANDWITHOUT MUCOPOLYSACCHA-
RIDOSIS UNDERGOING CARDIACVALVE REPLACEMENT
Constanze Bening, Helge Weiler, Ahmad Abugameh, Christian-
Friedrich Vahl
Department of Cardiothoracic and Vascular Surgery, Medical Centre
of the Johannes Gutenberg-University Mainz, Germany
Objective:
Progressive valve pathology is the most prominent
cardiac manifestation in patients with mucopolysaccharidosis (MPS).
Valve and papillary muscle thickening and short chordae lead to
valve regurgitation and are associated with systolic and diastolic
dysfunction. There is some evidence that differences in venous return
might cause decreased preload and reduced end-diastolic volume and
ventricular pressure, but the underlying mechanism remains unclear.
Methods:
Tissue from six patients (three MPS, three non-MPS)
undergoing aortic and/or mitral valve replacement was obtained from
the right auricle, transported in an oxygenated Krebs-Henseleit solu-
tion and skinned with Triton-X. We performed three experiments on
each patient (
n
=
18). The fibres were exposed to a gradual increase
in calcium concentration and the corresponding force was measured
and recorded.
Results:
(1) Calcium-induced contraction was statistically signifi-
cantly different between patients with and without MPS (
p
=
0.03).
