37
Medical Research Society
controls post-viral syndrome patients had significantly
reduced whole body leucine flux (116±12 versus 83±7;
p<O.OOl) and protein synthesis (101±10 versus 69±8;
p<O.OOl) while whole body leucine oxidation was comparable. (Figures are mean±SD and units ~mol kg-lh- l.)
Fractional MPSR (%h- l) was lower (0.046±a.008 versus
0.034±0.009 p<0.05). We tentatively suggest that the postviral syndrome is associated with reduced protein
synthesis in skeletal muscle.
(1) Halliday D. et al. Clin Sci 1988; 74: 237-240.
(2) Layman D.K. et al. Am J Physiol 1987; 253: E173-E178
139 MEASUREMENT OF WHOLE BODY PROTEIN TURNOVER IN MAN
USING A (2H5)PHENYLALANINE MODEL
GN THOMPSON, PJ PACY, GC FORD, H MERRITT, MA READ,
AJ NOBLE AND D HALLIDAY
Nutrition Research Group, Clinical Research Centre,
Harrow HAl 3UJ, England.
A method of measuring whole body protein turnover based
on primed constant infusions of (2 H5)phenylalanine (0.5rng!
kg/h) and (2H2)tyrosine (0.25mg/kg/h) has been validated
against the widely employed (13C)leucine method in 6
normal adults and in 2 children with Lesch-Nyhan syndrome.
To hasten achievement of isotopic plateaus, priming doses
of (2 H5)phenylalanine (0.5mg/kg), (2H2)tyrosine (0.25mg/
kg) and (2H4)tyrosine (0.08mg/kg) were given. Phenylalanine and tyrosine concentration (using a-methylphenylalanine and a-methyl tyrosine as internal standards) and
enrichment were measured in plasma by GCMS using previously described GCMS methods (1). Plasma a-ketoisocaproic acid (KIC) enrichment was used to calculate leucine
turnover; (2H5)phenylalanine and (2H2)tyrosine enrichments were corrected to mixed venous values (2). Phenylalanine hydroxylation and flux were calculated as described by Clarke and Bier (3) who demonstrated attainment
of tyrosine enrichment plateau after 6-8 hours. By using
the priming doses described above, enrichments of all
measured isotopic species reached plateau within 2 hours
of constant infusion. In adults the phenylalanine
method (mean±SD protein synthesis 3.00±0.15 g/kg/d,
catabolism 4.04±0.29) gave similar results to the leucine
method (synthesis 3.09±0.27, catabolism 3.70±0.35), and
both methods again gave similar values in each child. The
phenylalanine method appears to reflect protein metabolism in a similar manner to the leucine method. It is
comparable also in the short study period required, but
has the additional advantage of not requiring measurement
of expired CO 2 production rate or enrichment.
1) Schwenk WF et al. Anal Biochem 1984; 141: 101
2) Layman DK, Wolfe RR. Am J Physiol 1987; 253: E173
3) Clarke JTR, Bier DM. Metabolism 1982; 31: 999
140 Body cell mass following major electice surgery.
F. Carli and C. Freemantle (Introduced by Dr. J. Milledge)
Department of Anaesthesia and MRC Cyclotron Unit. Post
graduate Medical School, Hammersmith Hospital, London W12.
Surgery in normal SUbjects results in a short catabolic
period which is characterised by weight loss, negative
nitrogen balance with positive salt and water balance
suggesting a post-operative decrease in body cell mass.
The size of body cell mass can be estimated by measuring
total body potassium (TBK). Potassium is the most abundant
intracellular cation which is linearly related to the Slze
of the body cell mass 1• Limited data is available on :BK
during the post-operative period. 66 patients undergolng
either intra-abdominal, pelvic, orthopaedlc
cardla~
surgery were studied. Age,sex,body weight,helght, sklnfold
thickness were recorded before surgery. TBK wa~ measured
noninvasively by use of a whole body counter wlth a
0:
p
pr-ec ts Ionof' + 2't,. The measurements occurred before surgery,
and four and-seven days after surgery. The results of the
study are summarised in the table below.
Before Surgery
Mean + (1SD)
Abdominal
2811 (+142)
n=10
2661 (+404)
Pelvic
n=18
Orthopaedic
2582 (+685)
n=23
Cardiac
3321 (+185)
n=15
~**p
*p
0.05 **p 0.01
After Surgery
4 days
1 days
*
2510 (+668)
**
2654 ~+152)
**
2584 (+412)
*
2654 (+319)
***
2321 (+511 )
***
2312 (+555)
3113 (+149)
0.001
There was a significant drop in TBK in all groups
following surgery and the greatest fall occurred at day 4.
No correlation was found between the percentage of
measured over predicted and the post-operative TBK loss.
TBK fell by 3% after pelvic surgery compared to other
groups (1%) suggesting that the decrease in body cell mass
might be related to the severity of surgical trauma.
1. FD Moore et al. The body cell mass and its supporting
enviroment. Philadelphia 1963, WB Saunders.
THE ROLE OF ATRIAL NATRIUBETIC PEP1'IDE
IN THE NATRIURESIS OF BEAD-OOWN TILT
MJ ALLEN, VTY ANG and ED BENNETT
St George's Hospital Medical School, London
Head-down tilt results in atrial stretch, the release of atrial
natriuretic peptides (ANP) and a natriuresis, but a direct
cause and effect relationship has not been fully established.
Eight volunteers took 500mg lithium carbonate the evening
before each study and attended on 3 occasions. After a 60
min control period sitting upright they underwent a 3-hr
infusion of ANP (1.2 pmol/kg/min), a 3-hr placebo infusion
and a 3-hr period oflOohead-down tilt, in random order.
Fractional excretion of sodium was unchanged with
placebo, increased with ANP from 0.83 ± 0.16 to 1.12 ± 0.12
(mean ± SEM, P<O.Ol) and increased with tilt from 0.87 ±
0.12 to 1.34:t 0.10 (P<O.OOl). The urinary volume response to
ANP (5.8 ± 1.2 rising to 7.9 ± 0.5 ml/min) did not differ from
placebo. Tilt produced a diuresis (5.6 ± 1.2 rising to 10.8 ±
0.4 ml/min; P<O.OOl) which was significantly greater than
placebo or ANP (P<O.OOl) [probably reflecting additional
inhibition of vasopressin]. Lithium clearance (equivalent to
sodium clearance by the proximal nephron) increased with
both tilt and ANP. A delayed increase in sodium clearance
by the distal nephron was more marked with tilt than ANP
[perhaps due to changes in either aldosterone or a
hypothalamic NaIK ATP-ase inhibitor]. Haematocrit was
unchanged by placebo, showed a modest increase with
ANP (43.5 ± 0.9 to 44.3 ± 0.6: P<0.05), and a modest
reduction with head-down tilt (43.8 ± 0.9 to 43.1 ± 0.9: ns),
Plasma ANP was unchanged by placebo, rose with tilt from
8.1 ± 1.0 to 11.4 ± 2.5 (P<O.OOl) and with ANP infusion from
6.5 ± 1.4 to 32.3 ± 10.7 pg/ml (P<O.OOl). Plasma ANP was
significantly greater following ANP infusion than during
tilt even though natriuretic responses were similar. These
results suggest that ANP alone is a less potent natriuretic
than head-down tilt. This may be because ANP is not the
major determinant of the natriuretic response to tilt or that
the effects of ANP are dependent on other responses to tilt
such as a reduction in renal sympathetic nerve activity or
reduced activity in the renin-angiotensin-aldosterone axis.
141
142 EFFECT OF ABNOR~~ ~lliGATIVE INTRATHORACIC PRESSURE
ON ATRIAL NATRIURETIC PEPTIDE (ANP) R~'LEASE AND RENAL
FUNCTION IN HEALTHY MEN.
A WARLEY, F FONTES. M WILSON. A RAINE. J S~LING.
Osler Chest Unit and Nuffield Dept of Med. Oxford.
In health. inspiration is normally accomplished.by
enerating -5 cmsH20 intrapleural pressure (relat~ve to
~tmospheric). When upper (eg obstructive sleep apnoea -