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hemodynamic study, blood was taken from the pulmonary
artery (PA) for the ANF assay. The heart transplant
patients show a normal response of CO with increasing
work load. In the present study,acute exercise produced
a substantial increase in ANF concentration in PA, in
parallel with hemodynamic measurement.
Table 1. Mean ~ SD
Rest
Max Exercise
Recovery
ANF (pM)
30.54(~25.47) 53.45(~48.66) 37.78(!24.67)
+
+ ) 119.27(!14.03)
HR Beat/Minl04.45i-22.30)157.36(;18.19
RA mm Hg
0.72(- 1.19)
5.1 (- 4.66)
0.36(! 0.92)
PPA mm Hg 14.18(~ 5.06) 31.09(~ 4.76) 15.45(~ 3.67)
PCWP mm Hg 3.36(~ 2.73) 11.36(~ 3.96)
3.72(~ 2.94)
SAP mm Hg 109.36(~13.52) 134.18(~23.22) 100.18(~13.34)
co L/min
4.78(! 1.15) 14.9 (~ 2.63)
5.65(~ 1.5)
Our results indicate that in fact sympathetic nervous
innervation of the heart is not necessary for release of
ANF
85
INOSITOL PHOSPHATE PRODUCTION IN RESPONSE TO
AGONIST STIMULATION OF CULTURED NEONATAL RAT VENTRICULAR
MYOCYTES
MD GAMMAGE, A LOGAN. E McDERMOTT AND SD LOGAN
we thank the wellcome Trust for their support
Culture of neonatal ventricular myocytes offers a simple
system for the study of molecular events resulting from
receptor stimulation in cardiac cells; however the
receptor status of this culture system remains undefined.
Hydrolysis of inositol lipids to produce inositol 1,4.5
triphosphate which is released into the cytoplasm to act
as a second messenger has been demonstrated in response
to a)-adrenergic and muscarinic stimulation in adult
cardiac cells but the response in neonatal ventricular
cells has not been evaluated. Myocytes were dissociated
from ventricular tissue removed from 3 day SpragueDawley rats and following dispersion, equal aliquots were
dispensed to the wells of a 12-well microtitre plate.
The cells were cultured in inositol-free DMEM until
beating monolayers were established at 4 days. Cells
were then incubated in DMEM containing ['H]-myoinositol
(2 uCi/ml) for 48 hrs before being stimulated for 1 hour
by the addition of noradrenaline or carbachol in medium
that contained 10 roM LiCl. Total ['H]-inositol phosphates were extracted and separated by ion exchange
chromatography and results were expressed relative to
unstimulated controls. NA stimulation demonstrated a
sigmoid l~~-dose response ~vrve (control:_~3~6 cpm [mean
M: 130+8; 10
M: 164+7;
+SEM]; 10
M: 101+4; 3x10
3xlO- 6 M: 214+11; 10- 5 M: 220+12 cpm); carbachol stimulation required-higher agonist d~~es and peak r~~ponse was
lower (control: 93+6 cpm; 3x10
M: 105+9; 10
M: 125+7;
3x10- 5 M: 124~8; 10-4 M: 127~5 cpm ) ,
These data suggest that this neonatal ventricular myocyte
culture system offers a simple and convenient model for
study of intracellular second messenger production in
response to a)-adrenergic and muscarinic receptor stimulation; patterns of response appear similar to those
seen in published data on adult cardiac cells.
THE
EFFEX::T OF SUSTAINED INCREASE
IN WALL
STRESS
p
design. Hearts were studied from anirrals with a minimum
age of 3 rronths and within the weight range 300-400 g.
The relationship between level of wall stress and arrhythmia was U shaped with an optimal pressure of 100 mn
Hg. The results showed the same pattern in both groups A
and B, although the exact relationship varied slightly
such that in group A 60 mn Hg was associated with less
arrhythmia than 140 mn Hg, whilst in group B it was
associated with nore, In both groups 180 mn Hg was associated with significantly rrore arrhythmia than 100 mn Hg.
When the results from both groups are cont>ined an afterload pressure of 180 mn Hg is associated with significantly rrore ventricular arrhythmia than any other pressure.
Mean ectopic counts (as %) at each pressure: 60: 23.9,
100: 18.9, 140: 20.1, 180: 37.8. (180 vs 60-p<0.02, vs
100-p<0.01, vs 140-p<0.02).
Thus, although the hypertrophied heart derronstrates
some protection against arrhythmia induced by acute wa~l
stress increase, sustained high levels of pressure remcun
significantly rrore arrhytbrrogenic than lower levels. The
results indicate a possible mechanism for the observed
increased prevalence of ventricular arrhythmia in hypertensive patients and also derronstrate one possible mechanism for the previously noted deleterious effect of excessive pressure reduction in hypertension.
Department of Physiology, University of Birmingham,
Birmingham B15 2TJ
86
23
CN
ARRHYTHMIA IN HYPERTENSIVE HEARTS
M A JAMES and J V JCNES
CLINICAL IMPLICATIONS OF CEREBRAL BLOOD
FLOW CHANGES DURING CARDIOPULMONARY
BYPASS
87
GE VENN, K SHERRY, L KLINGER, S NEWMAN,
M HARRISON AND T TREASURE·
Department of Cardia-Thoracic Surgery, Middlesex Hospital,
London. UK.
We have measured cerebral blood flow (CBF), using intra-anerial133
Xenon clearance, before, during and following bypass, in 58 patients
undergoing coronary artery bypass surgery (CAB.S). Arterial press~
and perfusion flow on bypass were recorded continuously. Blood ll:C1d
base balance was maintained according to a pH stat protocol dunng
surgery with temperature adjusted arterial pH approximating to 7.40.
Cerebral metabolic oxygen usage (CMR02), and an index of cerebral
oxygen usage to delivery (CER02) was calculated at the time of each
of the three CBF studies. The patients underwent detailed
neuropsychological assessment before and following surgery.
CBF was correlated closely to PaC02 (p<O.OOI, 0.07 and 0.(05) and
CMR02 (p<O.02, 0.001 and 0.(01) before, ~uring and foll(j~g
bypass respectively. CER02 before and following bypass fell WIthin
the normal range whereas CER02 on bypass fell significantly
(p<O.OOI) to a median value of 0.28 suggestive of a perfusion
mismatch with CBF exceding metabolic demand. CBF on bypass was
independant of anerial pressure and pump flow indicating that the
integrity of vascular autoregulation is maintained during bypass.
.
A deterioration in neuropsychological performance compared With
pre-operative scores occurred in 33% of patients at eight weeks (70%
CL. 26%-40%). Neuropsychological impairment at eight days and
eight weeks did not correlate with changes in CBF, PaC02 , CMR02,
or CER02 during surgery.
On the basis of these data deterioration in cerebral cortical function
following CABS cannot be accounted for by changes in cerebral blood
flow alone. The data would, however, lend support the use of an
alpha stat, rather than ph stat, protocol during bypass. The lower
PaC02 for any given temperature that this requires ",:ould potenti~ly
abolish the period of relative cerebral hyperperfusion seen dunng
bypass. One may postulate that this would pot~ntially minimise the
incidence of perfusion related, micro-embolic, cerebral damage
occuring during bypass.
Department of cardiology, Bristol Royal Infirmary
we have investigated the effect of sustained levels of
wall stress on arrhythmia prevalence in hypertensive
hearts. 24 hearts from the spontaneously hypertensive rat
were studied using the isolated working heart roodel.
These were studied in two groups designed to COI'Iilat the
time dependent reduction in arrhythmia in this model. In
both groups 4 levels of mean 'aortic' pressure were
studied: 60, 100, 140 and 180 mn Hg. In group A each
pressure was studied for 20 minutes in a randomised
balanced cross-over design, in group B each pressure was
studied for. 5 minutes. in a randomised balanced cross-over
88
REGULATION OF INTRACELLULAR pH' IN
BEATING MAMMALIAN CARDIAC CELLS
P.L. WEISSBERG, P.J. LITTLE, E.J. CRAGOE
AND A. BOBIK
Baker Medical Research Institute, Melbourne,
Australia
The intracellular pH-sensitive, fluorescent probe
BCECF was used to investigate the role of Na+-W
exchange, bicarbonate and ATP in the regulation of