Formation of hydroxyl radial in acute myocardial infarction in man

J Mel Cell Cardiol

23 (Supplement

64 ENZYNE ACTIVITYOF

V) (1991)

HUMANXANTHINE OXIDASE

Car01 and Roger Shalah Abadah, Sawyer University of Bath, Bath, BA2 7AY UK

Harrison,

Department

of

Biochemistry,

oxidase has attracted considerable attention because of its The enzyme, xanthine proposed role as a source of free radicals in ischaemia/reperfusion damage. The relevance of xanthine oxidase in myocardial infarction has, however, been questioned to detect enzymic activity in human heart in view of the failure, of some groups, tissue, despite immunohistochemical evidence of its presence. We have purified human xanthine oxidase from breast milk, in amounts comparable with those obtained from bovine milk. The purified human enzyme is chromatographically homogeneous, but has xanthine oxidase activity (assayed by urate production) that is less than 1% that of the bovine enzyme. NADH-ferricyanide oxidoreductase activities of human and bovine enzymes are, however, very similar. These observations can be explained by the results of folate affinity chromatography which show that more than 95% of the human enzyme comprises the desulpho enzyme, inactive to xanthine. An analogous situation with the human heart enzyme would serve to explain the literature discrepancies, mentioned above.

65

FORMATION OF HyDROXYLsRADICAL IN ACUTE HYOCARDIAL INFARCTION IN HAN Cavallo *,Valter Pensa*,Maria A.Chessa *,Enrico Marco Tubaro,Giovanni Natale,Roberto Hospital,Roma and *Wellcome Tubaro * - CCU,S.Camillo Ricci,Filippo Milazzotto,Ezio Italia Research Laboratories,Pomezia,Rome (Italy) Dihydroxybenzoic acid (DHBA) derivatives of acetylsalicylic acid (ASA) are formed the possible formation in vivo by the action of hydroxyl radical (.OH). To evaluate we studied 9 patients (p) at of .OH in acute myocardial infarction (AMI) in man, first episode of AMI, treated with rtPA and 8 healthy volunteers (hv). All subjects blood samples were taken 30 min after the first dose received 100 mg ASA/d p.0.; (time 0) and then at 3-6-12-24-48 hrs and 5 days. Serum was analyzed by HPLC and electro chemical detection for 2,3- and 2,5-DHBA co; tent. 2,3-DHBA was present in all subjects with AMI, while it was undetectable in hv; Oh*aI 1%Zdhml Eq Oh33ch,ZhZ4h 48h!a 2,5-DHBA levels did not show statistically that significant differences between AMI p and hv. These data support the hypothesis .OH

66

formed

is

during

AM1 in man.

THE CON8INATION OF ZINC AND DESFERRIOXANINE PROVIDES PROTECTION TO THE HEART VIA BOTH 'PUSH'

AND 'PULL'

Vandong

Cardiac

Jiang,

Center.

Hen1

Schwalb,

Hadassah

University

We have

prepared

Gideon

Hospital a family

Uretzky and the

and Mordechai Hebrew

of compouoos

Chevion

University,

that

we

from the Joseph

Hadassah

Medical

(X) of the peak ventricular presrupre (P) and dp/dt of control recovery of these parameters in hearts perfused with MCJ-1,2, 116i13

for

normal

slnux

for

the

P, and 87+10, rhythm

MCJ treated

dose dependent. OF0

alone

is syneqisric

The protection into

cells,

hearts

Previously

by these and by virtue

bound,

123+20for

were

redax farm of the transitIon

153+15,

dp/dt

comblnatlon and approaches

compounds

lZO+tI

and available by the metal

(VF) and S&IO

Zn(His)Z

by 83.

effects

via

Likewise, (for

the

NSR),

and

demonstrate against

unique

of these

hearts

(II)

IZltll

that

desferrioxamlne

system.

phase.

l+l. 13+8and It1

The recovery

the durations

and (for

84+25, VF).

of VF duration

the protection

of the complex

stemnrng

and

respectively. vhile the increased to 85+12. 57+10 and

were IQ16

reduction

Research

Israel.

in the Langendarff

induced that

and from the efficient

by

of

those

These values

were

44

and

by such a Zn/[)FO

injury senders

(set)

while

(SK)

provided

from the displacement

iron (or copper) ("push" mechanism) free OF0 ("pull" mechanism).

S.26

zinc

NECIUNISNS.

Surgery

These compounds were used in the

ischemla/reperfusion

properties

complexes

Jerusalem,

in the reperfusion

the control

(3OmM) has provided

defense

of (MCJ-3).

group were 16t13 and and 3 (3OuM) significantly

far

These results

complete

is visualized

of the combined active metals

(p
fibrillation

we have shown that

by 19. and their

combination

protein

51$3 and

(NSR) and ventricular

School.

composed of combinations

of 1.O:l.O (MCJ-I), 1.0:0.75 (MCJ-2) and 1.0:1.25 (DFO) > at Zn:OFO ratios perfusate of rat hearts subjected to regional ischemia (10 mln) and reperfusion

Lunenfeld

to it

the

more

by zinc

heart.

permeable

of the "0".

binding

of this