Hyperdynamic circulation in cirrhosis: Physiology or pathophysiology?

GASTROENTEROLOGY

1993;104:1579-1584

CORRESPONDENCE Readers are encouraged to write letters to the editor concerning articles that have been published in GASTROENTEROLOGY.Short, general comments are also considered, but use of the Correspondence section for publication of original data in preliminary form is not encouraged. Letters should be typewritten double-spaced and submitted in triplicate.

Differing Chemical Content of the Neuronal Populations of Submucosal Ganglionic Plexus of the Enteric Nervous System Dear Sir: We re;ad the paper by Crowe et al.’ with great interest. expected from the earlier literature populations

that chemically

can be found within different topographical

the submucous plexus in the human large intestine. that substance P-, Leu-enkephalin-

and somatostatin-immunoreacplexus and the

region of the submucous plexus but were absent from

the Meissner’s

plexus;

similarly,

serotonin-containing

nerve cell

bodies were only observed in the outer submucous

nerve network.

Readers unacquainted

get the impres-

with the latest publications

HyperdynamicCirculation in Clrrhosis: Physiology or Pathophysiology? Dear Sir: Over the current similar conclusions

year, two independent by means of completely

sion that Crowe et al. are the first to show that “the different layers

protocols. l-3 Challenging

gested that the main cause of the circulatory

enteric plexus are not a single entity, neither in

or chemical

concerned

with this subject, the presentation

and discussion

is quite incorrect

to the reader. It

has been shown by our research team, albeit in studies of the small intestine

of a large mammal

tural* but also chemical

(that is, the pig) that not only struc-

differenceP

exist between the submuco-

sal ganglionic

neural networks.

It is evident from the structure

the intestinal

wall that these differences

of

exist also in the large

The authors conclusions

do not mention

as previously

that they have come to similar

reported by us (see 3-4). In both publica-

tions, it is stressed that the study of the porcine representative

of that of large mammals

small intestine

including

is

man. By not

to these works, not even from a comparative

viewpoint,

readers are led to believe that Crowe et al. should be credited with having found that the inner and outer submucous harbour

arterial pressure-is

chemically

fulfill different

different

functional

widely implicated

neuronal

populations

plexuses indeed and probably

roles despite the fact that this has been

in the above-mentioned

output

studies.

tion of the systemic arteriolar

resistance

arising

heart rate

and, possibly,

district.

left ventricular

end-diastolic

measuring the ventricular

volume,

diameter,

indirectly

decreased,

end-systolic

as would be expected

load, but actually

increased.

ascertained

was increased.

of heart failure, this suggests an enhanced

(diameter)

in a condition

vascular resistance

and arterial pressure

were

healthy controls.

not significantly

lar tone in determining

cardiac

crease before arteriolar We obtained,

vasodilation

healthy control

difference

maintenance

L-2020

capacitance

lar resistance

In any case, can in-

ensues.

of the splanchnic circulation

We observed (1) no statistipatients,

pattern

of

with” and without2

requirements

deriving from the

in the presence

of an increased

venous

appearing

l-2

bed and (2) a full-blown hours after taking up the

a maneuver associated with the translocation

of blood volume towards the “central”

recumbency,

to

of arterio-

when an expanded blood volume is

of such a posture

tient evaluation

respect

output

the hemodynamic

subjects and cirrhotic

~Groenenborgeriaan17 1

portion

in cirrhosis.

eventually

between

ascites, in the upright position

hyperdynamic

with

that cardiac

circulation.

needed to fulfill the hemodynamic

supine position,

that

in a different way, further evidence for a volume-

hyperdynamic

cally significant

however,

(the actual drive for carreduced

output

showed

Morewas not

whose systemic

This may have masked the importance

this study incontrovertibly

by

of reduced after-

be noted,

these results were obtained in a patient population diac afterload)

the

In the absence

cardiac preload.

volume

It should

~University of Antwerp (RUCA)

Crowe R, Kamm MA, Burnstock G, Lennard-Jones JE. Peptide-containing neurons in different regions of the submucous plexus of human sigmoid colon. Gastroenterology 1992; 102:46 l-467. Scheuermann DW, Stach W, Timmermans J-P, Adriaensen D, De Groodt-Lasseel MHA. Neuron-specific enolase and S- 100 protein immunohistochemistry for defining the structure and topographical relationship of the different enteric nerve plexuses in the small intestine of the pig. Cell Tissue Res 1989;256:65-75. Timmermans J-P, Scheuermann DW, Stach W, Adriaensen D, De Groodt-Lasseel MHA, Polak JM. Neuromedin U-immunoreactivity

and, possibly,

vascular

Lzborafog of Cell Biology and HistoLou Antwe@ Belgium

they sug-

abnormalities

Lewis et al.’ showed that, in supine patients with cirrhosis,

dependent D. W. SCHEUERMANN, M.D. J.-P. TIMMERMANS, Ph.D.

assumption,4

expanded blood volume rather than vasodila-

over, the left ventricular

intestine.

referring

cardiac

coupled with reduced systemic

in the introduction

and misleading

a well-established

in cirrhosis-increased

terms.” Given the numbers of publications

groups have reached different experimental

of the submucous structural

of the pig and its

regions of

They point out

tive nerve cell bodies were present in Schabadasch’s intermediate

It is to be

distinct neuron

in the nervous system of the small intesbne

coexistence with substance P and CGRP. Cell Tissue Res 1989;258:33 l-337. 4. Timmermans J-P, Scheuermann DW, Stach W, Adriaensen D, De Groodt-Lasseel MHA. Distinct distribution of CGRP-, enkephalin-, galanin-, neuromedin U-. neuropeptide Y-, somatostatin-, substance P-, VIP- and serotonin-containing neurons in the two submucosal ganglionic neural networks of the porcine small intestine. Cell Tissue Res 1990;260:367-379.

by Lewis et al.’ was performed

of a

area. Because paafter 30 minutes of

this may explain why a reduction of peripheral

vascu-

was not disclosed.

In the light of these results, the interrelationship diac output and systemic vascular resistance respect to the traditional

between

view4 (not a primary reduction

tance followed by a compensatory

car-

appears reversed with in resis-

increase in cardiac output, but a

1580

CORRESPONDENCE

primarily than

increased

normal

reduction

in systemic pressure

logical

point

adaptation

a primary

pathoadrenergic

blood

splanchnic

area in the upright

the central

and systemic

cannot

be said

where

the upright

in patients

blood

again

activation

of vasoconstrictor

putative

but

pressure

homeostasis

very

retention

volume

likely

trend

vasodilation

to mainly

fit with

within

of the

within

The

cirrhosis

and

hemoa

Blood

to be paid

was

assumption

of

the fundamental

although

in the advanced

On “DP”

it ap-

nous

by the Kodak

in high

code to be triggered.* lipase

activities

not a myth,

and requires

strictor

systems

further

investigation.

vasodilation

in advanced

a compensatory

activation

to be balanced;

to know

why it occurs

concentrations

of >4000

U/L

of

dynamic

cirrhosis

is

by the Kodak

Ektachem

gered

of the reported

of vasoconstill needs

Clinical falsely present

by Bilodeau,

in both

Chemistry elevated

cause

and the

cases shows

that

is designed when

reported

limit

of the

were not mentioned

and the “DP”

lipase activity

for this

the authors the upper

above

of endoge-

no result

et al. The fact that no results Analyzer

the mean-

activity

as the other

These details

Slide (LIPA)

serum

However,

dilution,

the

and no result

the presence

(two times

range for this method).

of the authors,

dilution,

after obtaining

twofold

can be diluted

flag is obtained.*

only as “lipase

considering

indicatlevels of

in the paper,’

analyzer.

Therefore,

for an initial

in the paper arteriolar

without

rate

in the mea-

of high

one

reported

inter-

the endogenous

the sample

S. Apple,

Ektachem

Slides

code is triggered

the “DP”

cases

code was interpreted

range,”

code

Fred

analytical

the reaction

When

even after a fourfold

stages

cirrhosis. In conclusion,

Dr.

obpro-

glycerol

or the presence

without

in both

code was present

“DP”

Chemistry

and a “DP”

activity

his data,

glycerol

of the

is consumed.

a result

to me that

the analyzer

is part Clinical measuring

ele-

were

glycerol

endogenous

In such an event,

until

ing of the “DP”

falsely

is so high that it may interfere is given

glycerol.*

reviewing

to start

glycerol

levels of lipase

confirmed

against

it is designed

and reanalyzed

in which interference

Although

of lipase Ektachem

is protected

no result

ing high

cases

Analyzer.

action

concentration

surement,

was given

an

to counteract

vasodilation.

is fulfilled,

in

range by

distribution,

but the price

occurs

activated

glycerol

endogenous

towards

Although

volume

the

position.

the normal

is also needed

hypothesis6 what

in this set-

trapped

advanced

to arteriolar

Thus,

because

after the endogenous

redistribution.3

was achieved,

this method

that

Therefore,

Ektachem

the

(LIPA),

two

due to glycerol

in the Kodak

suggesting

to be a function

described

results

through

measurement

position,’

were strikingly

of blood systems

of sodium.’

the peripheral

with

on the Kodak

ference

and redistributed

systems

are a function

and sym-

tained duction

lipase

con-

in the supine

and not suppressed

the supine-induced

pears

posture

a

serum

of healthy

volume,

circulations

dynamics

renal

blood

vasoconstrictor

posture

appears

at the

attempting

Bilodeau’

vated

that

was normal.

pattern

of an expanded

condition

A glance before

from

or the supine

volume

as an ex-

the renin-angiotensin

did not differ

in the upright

arterial

abnormality?

cirrhosis,

systems

circulation

has to be given

distribution

same

Dear Sir:

from a physio-

to a hypervolemic

circulatory systems

the hemodynamic

ascites,

This aims to maintain

he expected

the hyperdynamic

In preascitic

effective

resistance). as would

Absence of False Elevations With Kodak Ektachem Lipase

of a greater

with a compensatory

Recently,

consider

of vasoactive

conclusion.

ting,

vascular

preload]

of view.

than

trols either

[as a consequence

cardiac

of physiological

activity

output

homeostasis

Can we now rather

cardiac

supine-induced

arterial

pression

GASTROENTEROLOGY Vol. 104, No. 5

were given

flags were

Kodak

to prevent endogenous

trig-

Ektachem reporting glycerol

is

in the specimen.

M. BERNARD1 Ph.D.

Patohgia Medica I

GEORGE

PolitlinicoS. Orsola

Senior Technical Specialist

BROTEA,

Via Massarenti, 9

Clinical DiagnosticsDivision

40138 Bologna, Ifa&

Eastman Kodak Company 343 State Stfzef

1. Lewis FW, Adair 0, Rector WG. Arterial vasodilation is not the cause of increased cardiac output in cirrhosis. Gastroenterology 1992:102:1024-1029. 2. Bernardi M. Di Marco C, Trevisani F, De Collibus C, Fornale L, Baraldini M, Andreone P, Cursaro C, Zaca F, Ligabue A, Gasbarrini G. The hemodynamic status of preascitic cirrhosis: an evaluation under steady-state conditions and after postural change. Hepatology 1992; 16:34 l-436. 3. Bemardi M, Fornale L, Di Marco C, Trevisani F, Baraldini M, Pasini P, De Collibus C, Ligabue A, Gasbanini A, Colantoni A, Gasbarrini G. Systemic hemodynamics in decompensated cirrhosis: effects of posture (abstr). J Hepatol 1992; 16 (Suppl l):S30. 4. Sherlock S. Vasodilation associated with hepatocellular disease: relation to functional organ failure. Gut 1990;3 1:365-367. 5. Bernardi M, Fornale L. Di Marco C, Trevisani F, Baraldini M, Pasini P, De Collibus C, Zaca F. Gasbarrini A, Sica G, Pula B, Gasbarrini G. Impaired supine-induced natriuresis in cirrhosis with ascites: role of hemodynamic and hormonal factors (abstr). J Hepatol 1992: 16 (Suppl l):S30. 6. Schrier RW, Arroyo V. Bernardi M, Epstein M, Henriksen JH, Rod& J. Peripheral vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology 1988;8:1151-1157.

Rochester, New York 14650 Bilodeau L, Grotte DA, Preese LM. Apple FS. Glycerol Interference in Serum Lipase Assay Falsely Indicates Pancreas Injury. Gastroenterology 1992; 103: 1066- 1067. 2. Eastman Kodak Company. Test Methodology. Kodak Ektachem Clinical Chemistry Slides (LIPA). Rochester, NY: Eastman Kodak Company, 1992. 1

Reply.

Examination

for the serum

of the

lipase

(LIPA)

1986

time of our study* and the revised ogy3 for the serum

Ektachem

test methodology’

assay that was in practice

lipase (LIPA)

1992 Ektachem

assay that was implemented

our study was completed

show that there are differences

claimed

glycerol

by Kodak

about

between

sions. The only comment

about

that a “DP”

substrate

lipase glycerol

flag indicates

activity

above

Nowhere

can be diluted

may be normal.

glycerol

the dynamic

concentration.

that glycerol

Although

during

the 1986 and 1992 ver-

U/L)

in the 1986 version is not given

states

This may indicate

(2000

out or after dilution a result

after

in what is

in the 1986 version

depletion. range

the

test methodol-

a

or a high does it state

the lipase activity by the Ektachem,