Download Alteration in the Cycle Length Dependence of Action Potential

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calculated. HT p.tlmts were divided into two groups accordingto their response to
&blocker: good rerpondsrr (n=35) and noniespondwr (n-1)who w e d e R d
by a BP fall >25/10 mmHg of 45/10 mmHg. rerpedivdy. Thdr genomic D N k
were analysed for genotypes of exon 5 polymorphism b identifying the presence
(+) or absence (-) of the M restridion rite of FCR-empli exon 5 DNA
fragments. Rnu)t.: The genotype dislributlon of Fdrl--.
Fdrl-+ and Wi++
was
4:19:12 in the good rospondera and 8:134 in the non-rerponden ( ~ =4.929.
2
0.1>pW0.05).
SignMcanl diffamncorware observed in the frequency of the Fokland Fdrl+ alleles among chromcnomes in the good rasponden (2743) and nonresponden (2921: x2 a.423. p<0.05). Cornpariaom of changes in BP among lhe
three genotypeswas arreued by one-way analysis of variance (meaniSEM):
M-+
FdrlM++
F
P
16
- n
12
32
Age (Y)
52.67i3.83
57.3li1.80
54.75f2.36
0.91 0.407
Weight (Kg)
83.43i6.20
81.oM3.57
77.933.45
0.30 0.743
SBPpre
165.5053.37 17O.CW2.68 178.44i6.33 1.98 0.147
150.83f5.36 146.78i3.82 147.56f4.62 0.18 0.839
30.88f5.38 2.80 0.069
14.67f4.09
23.28i3.05
0.17fo.03
2.18 0.122
ASBP/SBPpre 0.09M.02
0.14fo.02
ga.g~i4.x 1w.mii.a iio.8ii3.93 3.57 0.035
m . i g ~ m 0.14 0.871
90 wf3.42
88.9iii.88
20.63i3.45
4 01 0.023
ADB$lt
8.33f2.40
15.75i1.95
0.18fo.03
3.67 0.032
ADBP/DBP,,,
0.08iC 03
0.15iC.M
gpst
;;p
Conclusions: The results show that subjects homozygous for me Fokl++ have a
better response to p-blocker therapy. indicating a correlation between G,a
genotype and P-blockademediated lowering of BP in this HT group. This finding. if
confirmed in a larger study. could have clinical implicationsfor treatment of EH.
MU
A~TERATION IN THE CYCLE LENGTH DEPENDENCE OF
ACTION POTENTIAL DURATION BY ISCHAEMIA IN THE
HUMAN HEART - RELEVANCB TO ARRHYTHMOGENBSIS BY
A PREMATURE BEAT
19~
clinical features; hypogonadotrphic hypogonadism (IH€i)and anemia
(absence of olfaction). This disorder can be inherited as an autosomal
dominant, autosomal recessive, or X-linked trait or can be sporadiiin
origin. KS affects 1 in l0,OOO males and 1 in 50,OOO f d c s ,
suggesting that the X-linked form is more common. The KAL gene is
thought to be responsible b r the X-linked brm of KS has been isolated
on Xp22.3 and its product is thought to play a role in the growth of the
olfactory nerve into the forebrain and the concurrent migration of
GnRH neurons along it into the mediobasal hypothalamus.
We report a study performed on a patient group consisting of patients
,
KS ~ 8X-linked
,
KS FI 1
With autosod dominant KS ~ 3sporadic
and MH n=4. The presence or absence of each of the 14 CXOIIS of the
KAL gene was investigated using the polymaase chain m a i o n (PCR).
DNA was extracted h m whole blood, and lug was used together with
lOmM dNTP's and ImM MgCI, in a 30 cycle reaction (denature WO-1
min, annealing 55"-lmin, extension 72O-lmin).
RESULTS: All 14 exons were present in patients with autosomid
dominant KS; this is as expected since KAL is not thought to be
involved in this form of KS. Two patients had an exon missing in the
sporadic group, and in the X-linked group there were four patient With
one exon missing each and three with complete gene deletions. In the
LHH group only one patient had one exon missing. This data suggests
that complete deletions or complete absence of an exon is rare and that
the disease is probably due to point mutations in the coding, promoter,
or downstream regions of the KAL gene.
P TAGGAFLT,PMI SIPITON,MR BOYEm,MJ LAB and RH
SWANTON
Departments of Academic and Clinical Cardiology,
UCL Hospitals,
Departments of Physiology,
Charing Cross Hospital, London anduniversity of
Leeds
We present evidence in the human heart that
ischaemia alters the normal relation between
action potential duration (APD)and cycle length
in a manner which may greatly facilitate
arrhythmogenesis by apremature beat. Monophasic
action potentials were recorded in 14 patients
(22 sites) from the right ventricular septum
during angioplasty of a mid left anterior
descending coronary arterylesion. Atest pulse
sequence with shorter and longer coupling
intervals was incorporated.
Under control
conditions test beats with the shortest coupling
interval had the shortest APDs and test beats
with the longer coupling interval had a longer
APD. This resulted in a rising curvilinear
relationship between increasing APD and
increasing diastolic interval. During ischaemia
the APD dependence on cycle length was minimised
thereby flattening the curve: eg, at shortest
intervals APD shortening (control 16.7*1.7ms;
ischaemia 0.14i1.2ms; P<O.OOOl) and at long
intervals APD lengthening (control 5.5k2.0ms;
ischaemia 0.5*1.0ms; Pc0.05). We conclude that
ischaemia rapidly diminishes the cycle length
dependence of APD in the human heart. This may
result in a voltage gradient sufficient to
reexcite across and ischaemic border zone at
short coupling intervals.
Mb5
MUTATION ANALYSIS IN PATIENT WITH KALLMANN'S
SYNDROME USING THE POLYMERASECEAIN REACTION
V M Duke, P A d e Zoysa, R Quinton 8 n d P M G Boulous.*
Division of Endocrinology, R F H W & UCLMSJoint Departments of
Medicine, Rowland Hill Slreet, London NW3 2@.
KallmaM'sSyndrome(KS) is described by the association of two main
M66
MEASUREMENT OF LIPID PROFlLES POST-STROKE
RJ BUITERWORTH. WJ MARSHALLand PMW BATH
Departments of Medicine and Clinical Biochemistry. King's College
School of Medicine and Dentistry. London. SE59PJ
Introduction: Atherosclerosis is a major risk factor for stroke
whilst serum lipid profiles may predict atherosclerotic risk. Lipids
change following myocardial infarction but less is known about
stroke.
Mctboda: Fasting lipid p f i l e s were obtained from 57 acute strdrc
patients (17cerebral infardon.4 primary intracerebra! hacmorrhage)
at <48 hours, one week and three months post-ictus. Stroke was
diagnosed on clinical and radiological grounds. Patients admittedon
hypcrlipidacmic treatment were excluded.
Results: Significant falls in total cholesterol
calculated LDL
cholesterol (LDL) and HDLcholesterol (HDL)were observed
between admission and one week: in contrast. no change in
triglyceridcs o c c u m d (table). There was no difference in total
cholesterol between admission and at 3 months: mean (SD)5.81
(1.51) vs. 5.98 (1.36). difference -0.17 (95%CI -0.43 to 0.09.
2p=O. 19. n=32).
Conclmsions: Total. HDL-and LDLchdesterd m u ~ u ~ m c oall
ts
fall significantly in the first week following stroke as occurs in
myocardial infarction. The mechanism is *far unexplained. We
suggest patients should be screened on admission or three months
after stroke to avoid inaccurate lipid measurements. Koowlcdge of
lipids after stroke may aid prevention of recurrent vascular dipcase
includingstrokeand myocardial infadon.
(To,
Table. Serum lipids at admission and I week post- stroke,
comparisons by paired t t a t .