Ischemic-reperfusion injury and histamine release in isolated perfused guinea pig heart: Role of free radicals

Pharmaco~gicalResearchCommunication~VoL2~Supplement~1988 ISCHEMIC-REPERFUSION

INJURY AND HISTAMINE RELEASE IN ISOLATED

PERFUSED GUINEA PIG HEART: E. Masini,

99

F. Gambassl,

ROLE OF FREE RADICALS.

B. Palmeranl,

A. Pistelli,

E. Giannella

and P.F. Mannalonl. Department

of Preclinical

of Florence, Key words:

and Clinical

Viale G.B. Morgagni

65, 50134 Florence,

of oxy-radicals

in the biochemical

ciated with ischemia and reperfusion

cance,

University Italy.

Free radicals;ischemia-reperfusion;hlstamine

The involvemen~

tissues

Pharmacology,

is far from clear. oxy-radicals

are involved

as mast cell histamine kocyte chemotaxls

secretion

their pathological

(Mannaioni

signifi-

process

et al.,

such

1988),

leu-

1985), platelets aggregation

1985) and high affinity

14C-y-amlno-buty-

in the CNS (Debler et al., 1983). As f a r a s

cardiac histamine provided evidences

is concerned,

our recent experiments have

that plasma histamine

creases during a subacute (Masini et al.,

events asso-

of cardiac and peripheral

in physiological

(Martin et al.,

(Del Princlpe .et al., tic acid uptake

Beside

release.

significantly

coronary thrombosis

in-

in the awake dog

1985) and a release of histamine

is observed

when the isolated guinea-pig heart is reperfused after 30 min of global and zonal ischemia

(Mannaioni

et al.,

1988).

Aim of the present

study is to provide further informations

on the biochemical

and morphological

changes occurring when

the heart is perfused with oxy-radical

generating system

(FeC13 I0 p M plus ADP 100 ~M) and/or by multiple release of the left anterior descending Under these conditions,

a differential

and lactate dehydrogenase tected,

reperfusion

phase.

xidation product,

release

of histamine was

liberation of histamine

In left ventricular malondialdehyde,

0031-6989/88/20S10099-2/$03.00/0

(LAD) coronary artery.

(LDH) in the perfusates

showing a preferential

legature and

samples

dein the

the lipid pero-

increased both in the

© 1988 The Italian Pharmacological Society

Pharmacologica/ ResearchCommunications, Vol. 20, Supplementl, 1988

100

ischemic

and reperfusion

phase.

The amplitude

was not modified during all the experimental

of contraction period,

while ven-

tricular arrhythmias were present mainly during reperfusion. The perfusion with FeCI3.ADP enhanced release of histamine, schemia-reperfusion trapper agent,

the release

significantly

of histamine

the basal

induced by i-

and the incidence of arrhythmias.

N-t-butyl-g-phenylnitrone

basal and ischemic reperfusion lease and also the incidences

A spin

(BPN), reduces

evoked histamine

the

and LDH re-

of reperfusion-induced

arrhyth-

mias. Our results indicate that oxy-radicals

release histamine from

tissue stores and evoke the appearance

of arrhythmias.

pharmacological inactivation

control of oxy-radicals

production

could be viewed as a tool for limiting

and reperfusion

induced

tissue

The

or their ischemic

injuries.

References Debler E.A., Sershen H., Lajtha A. and Gennaro J.F. Trans Am. Soc. Neurochem. 14: 93-97.

(1983)

Del Principe D., Menichelli A., De Matteis W., Di Corpo M.L., Di Giulio S. and Finozzi Angi6 A. (1985) FEBS Lett. 185: 142-146. Mannaioni P.F., Giannella E., Palmerani B., Pistelli A., Gambassi F., Bani Sacchi T., Hianchi S. and Masini E. (1988) Agents and Actions 23: 129-142. Martin W., Losche6 G., GUnzler W.A. and Floh~ L. (1985) Agents and Actions 16: 48-49. Masini E., Planchenault J., Pezziardi F., Gautier P. and Gagnol G.P. (1985) Agents and Actions 16: 227-230.