Download Left Ventricular Diastolic Filling is Improved by Atrial Natriuretic

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acid/ 9,12 l i l e i c acid (96MR)and thiobarbituric acid reactive
substances (TBARS). The serum dcsfcnioxamine-chelatable iron
(DFx-iron) was takcn as a measure of potentially 'catalytic" iron.
Results expressed as mean (SEM).
All indicators of free radical activity were significantly elevated in
active CFA compared to controls (P<O.Ol)*. The changes in DFxiron in active and inactive CFA were also significantly different
(3.8f1.7 cf. -0.9k0.8) (P<0.02). as was the change in 96MR
(active CFA 0.5k0.2 cf. inactive -0.4i0.1)(P<O.OI). These results
confirm the elevation of markers of lipid peroxidation in CFA and
suggest that this may be related to changes in the free iron available
for initiation of this pathological process.
duration (APD). Although glibenclamide.an inhibitorof the K A T ~
channel, has been shown to variably inhibit both the emux o f K + andl
APD shortening in multicellular cardiac preparationsduring
ischaemia, and a causal association between the two events
suggested, the simultaneous assessment of the effect of
sulphonylureaso n repolarisation and K+ efflux has not becn
investigated in the intact heart. Measurementsof monophasic
,
with suction electrodes and simultaneous %Rb efflux have been
investigated in l em t hearts paced at IHz perfused at 6ml g-1 m i d
with Krebs-Henseleitsolution (%M HCQ-; M)c).Heart? were
loaded with MRb for 2 hours and washed with WRb-free solution for
10 minutes before a 30 minute period of low-flow ischacmia (7.5% of
control flow). 4 minutes of ischaemia caused s b n i n g of the APD
from 200 2 msec to 185 + 9msec (-7%; n = 4). During the same
intervention there was a 4.7-fold increase in the unidirectional86Rb
efflux rate constant assessed by on-line flactivity counting (control =
0.01 i 0.mmin-1; ischaemia = 0.047 i 0.00s min-1). Addition of
IOpM glibenclamide to the perfusate for 30 minutes prior toand
during ischaemia caused an increase in APD following induction of
ischaemia(from 211 i4msecto240i4mscc;-14%;n=4).
Addition of glibenclamide partially inhibited the increase in &Rb
efflux compared to hearts not perfused with glibenclamide(0.039
0.003min-1 c/. ischaemia above). These results demonstrate that at a
concentration of glibenclamide thal prolongs APD following
induction of ischaemia there is c 22% inhibition of nel K+-equivalent
cfflux when cornpared to hearts not perfused with glibcnclamide.The
results suggest that although glibenclamide may modify APD during
ischaemia by inhibition of the K A Tchannel
~
it also probably has
significant cffccts o n other determinants o f repolarisation.
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LEFT VENTRICULAR DUSTOLIC FILLING IS
IMPROVED BY ATRIAL NATRlURETIC PEPTIDE IN MAN
PBM CLARKSON. TM MACDONALD, C MACLEOD. Nh4 WHEELDON.
Department of Clinical Pharmacology, Ninmells Hospital and
Medical School. D u n k DDI 9SY. Scotland, UK.
D
M k 25-34
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SS-64
4.31 (0.24)
s.on (0.I , i
5.86 (0.31)
7.13 (0.95)
4.45 (0.23)
5.04 (0.20)
S.97 (0.27)
1.4 (0.89)
5.5(1.1)
6.1 i i . i i
6.4 (I.I )
6.3 (1.1)
<O.oOI
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<u 001
N.S.
<o.M)I
N.S.
Thac dam
that SeNm chdac~mlanantrations lrrociaied wiiti
impulsive khviau wch as purruicidc an lower lhrn thm of Ihe control
populPlion as nugeacd by 10mcepidemiological rtudia. More rcrwrch i s
nscdcd to dim and clarify these findings and to JSSCSS ~ h e i h c m
r y causal
relriionrhipr which nuy exia bctwcn chdc~eroland iinpulsiwncss
1s GLIBENCLAMIDE INCREASES ACTION POTENTIAL
DURATION WITH PARTIAL INHIBITION OFeSRUBIDIUM
E F n U X DURING EARLY MYOCARDIAL ISCHAEMIA
HWL BETHUL. JI VANDENBERG. J CROWLEY. AA GRACE
&parlmcnl of Btochrmitlry, university of Cambridge, Cambridge
Activation of K A Tchannels
~
during myocardial ixhaemia is thcaght
to contribute to K+ efflux leading to a decrepse in action potential
Objective Atriopeptin 111 has been shorn to induce early relaxation
of isolated mammalian papillary muscle. We designcd this study to
test the hypothesis that atrial natriuretic peptide (ANP).a stn\cturally
related peptide released predominantly from the atria, has a
physiological role in modifying diastolic filling in man.
Design und Methods 10 normal male volunteers participated in a
randomised, double-blind crossover study comparing BNP with
placeb (05% (w/v) saline). Mcasunments of (a) the ratio between
early and late peak transmitd flow velocity (EIAmax) @)
isovolumic relaxation time (WRT) and (c) aortic stroke distance
(SD) were made using Doppler echocardiography combined with
phonocardiography. and measuremarts of heart rate (HR) and blood
pressure (BP) were made using a semi-automated blood pressure
monitor.
Recordings were taken after Ihr of supine bed rest (baseline) and
after 30 minutes of stepwisc infusions of ANP in doses of 0.5, 1.2.5,
Spmol/kg/min (OSA, IA. 2SA, 5A) or placebo.
Results Changes from baseline w m calculated and results are
expressed as the mean difference compared with placebo and the
associated 95% CI (* flO.05. t e . 0 1 ) . UA,
is significantly
increased with increasing doses of ANP compared with placebo:0.5A 0.29(-0.06to 0.65). IA 0.43(0.13 to 0.72)f. 2.5A 0.25(-0.11 to
0.61). 5A 0.4q0.02 to 0.89)*, whereas IVRT is significantly
decreased:- OSA -3ms(-5.8 to -0.2)'. I A -2.4ms(-6.5 to 1.7). 2.SA
-4.4ms(-7.9 to -0.9)*, 5A -5.9ms(-9.2 to -2.6)t. No significant
changes in BP, HR or SD were observed.
Concluswns
ANP decreases lVRT and increases WA,
suggesting that diastolic filling is improved by ANP in man.