The effect of PAF-receptor antagonist Kadsurenone on the cardiovascular effects in the rabbit infused with synthetic platelet-activating factor (PAF)

PROSTAGLANDINS

l’HE

EFFECT

OF

THE

RABBIT

INFUSED

lG.

Montr\xchlo,

lG.

Emanuel11

OG.

dl

dl

Alloatti.

study

Mariano.

and

07065

evaluates

cardiovascular

dl di

der

alterations

NJ

before

and

the

effect that

depression

lution

were

0.25%

BSA

of

and

I”

b.w.

fresh

dllutlons

Kadsurenone

The

of

by

occurred

(141.6~

with

(66.65

12.9%).

(46.5+

20.4%),and

max

a

LVEDP

completely I”

all

(phases

i.e.,at ll.S%).MAP

sec.the

prechallenge

to

Kadsurenone

lst1ng

iS for

cells

s

seen

applied

fall

in

signlflcant

cardiovascular

probably

were

values

wlthln

a

lnhlbltor

(1.e.

platelets

after

by

were

effective

segment

reduction

30-60

mln

of

and

OCTOBER 1985 VOL. 30 NO. 4

I”

neutrophilsl

with

all

slteratlons

and

after

PAF

rondurllor

1 Isfed

1”

I.VtDl

on

of

or

I.VPc Ci

Pretr,*aLme”t

*11:1

as

the

conducClol

hemodynnmlc in I”

alte.

synthf.tl.

(‘14.5,

+10.4%).

data

The-

reti,r”e,

synthetic

on

11;

phase max

PAF. suggest

cardiovascular

receptors

cardiovascular

.,sso-

(67.r,+lO.l%),

parameters

These

Induced to

thre, I.Vt:DI

R rno
(127.2

All

lnfuslon

PAF

or

TPR

rile-

*i!hlt

(‘I’J.I.b:,%l,

see”

rabbits.

blndlng

an

lirmodynnmli

Kadsurenone

t-test.

control

synthetic on

by

(108.3+2.4%),LV(+)dP/dt

Student’s

Ihe 0.35

decrrase

well

of

with

(75.9+0.2%) the

observed

antagonism

as

lher

after

f18B:C*I.~%r

(163.0+10.8%1.

the

nln

occurred

MAP

magnitude

for

15

(35 see-3mln):

depresslo” 1”

M

(l~l.r;~;‘~.4%l,

(66.1r10.5%).

pretreatment

(120.5+7.8%),CO

alterations

competltlve

ST

LVPs

(122.1+13.4%).TPR

RAP

0.010

(72.3-10.R%)-;~n~l

sec):increase

II

~.v.~nfuxlon

thnL

LVPs

f‘AF

cont.IlnlnK

were

(71.1~B.O%).CO

and

et

depresslo”.

xn

expr’r‘l-

Kodsurenonr

for

associated segment

Phase III

of

characterized 100%)

anelysls,

(96.2+8.4%).LVEDP

(~(0.05)

as

reduction

particularly

LVPs

(87.5+15.O%),RAP were

the

changes

ST

of

max

A marked

I,II,III)

for

mm)

(262.0+50.1%)

abrogated rabbits.

DMSO

~~M/rnl

PBS

(104.1+4.B%)

II(ZO-35

(60.8+9.4%3.

TPR

in

0.05

thermodl-

synthetic with

received

(123.4+12.3%),MAP

CO

1”

rabblts.Thls 90

data

1”

give

values

(78.3$.4%),MAP Phase

pretreated

artl’rla

the

sets

continuously

purpose

ventrlcu1.s:

by

of

mir

segmcn’

mean

(CO)

W30

(HR),ST left

ug/Kg

dissolved

ECG

(77.6+21.O%),:V(+)dP/dt

rise

Kadsurenone

the

evaluated

rate

following

0.8

induced

cardlnva-

parameters

and

2.0+0.6

The

physiologic

rabbits

sec):transient

max

decrease

arrhythmias

PAF-Infused

for

TPR(124.2,32.0%).

elated

(max

rabbit.

output

control

tachycardia

(lo-20

83.O%l,LV(+)dP/dt

ratlons

PAF

Kadsurcnonr

were

were

to

before

of the

and,

(75.6+lO.B%).LV(+)dP/dt

Resrarcl

I-O-octadecyl-2.

end-diastolic

with

was

controls,3

of

the

(TPR).The

made

min

as

marked

I

(Italy1

Dohme

LVP(LV(+)dP/dtmax),

rabbits

were

synthetic

a

and

Kadsurenone

prolonged

and

and

PAF:heart

of

infused 5

i.v.30

phases.Phase

in

Meda,

TOHINO

Kadsurenone

(RAP),cardiac

were

45-50°C

PAF;J)

(BB.B%l

increase

near

at

and

resistances

rabbits

admlnistered

followed

also

‘E.

antagonist

in

synthetic

increase

pressure

bradycardia(91+4.6%

sequential

It.

III;‘Dipar:1-

10126

infusion

PAF)

systolic of

solution;Z)

PBS

l.v.lnfuslon

sec.

changes

6

14 Sharp

i.v.

with ECC,

of

rate

M solution.

synthetic

transient

Ragnl,

Medica

Polonia

the

following

i.v.infuslon

saline

Into

of

arrhythmias

se

the

peripheral 1)

0.014

was

lnfuslon

R.

PAF-receptor

after

pretreatment

atria1

total

sterile of

Tetta.

Merck

specific

occur

arrhytmias,

right

performed:

ml/Kg

15-20

the

conduction

method,

ments

DMSO.

of

after

(MAP),mean

C.so

Research,

without

(LVPs.LVEDP),maximum

pressure

ly

min

and

pressures

C.

EFFECTS

(PAF)

Nefrologia;*Clinica

(synthetic and

monitoring

60

CARDIOVASCULAR

(USA)

changes

with

continuous

THE

FACTOR She”,

Torino

Arthritis

acetyl-sn-glyceryl-3-phosphorylcholine scular

ON

5T.Y.

Cattcdra Universitl

Membrane Rahway

This

F.

Animale;

of

KADSURENONE

PLATELET-ACTIVATING

Immunopatologia,

Laboratories,

the

‘NTAGONIST

SYNTHETIC

G.Camussi.

Blologia

$Departme”t

on

WITH

and

LaboratorIo mento

PAF-RECEPTOR

elthrr

11, ths

change: cl~cu.

tissues.

711