Inhibition of neutrophil accumulation into ischaemic-reperfused myocardium in the rabbit by trimetazidine

J Mol

O-17-4

Cell

Cardiol

24 (Supplement

LEUCOCYTE PERMEABILITY

I) (1992)

DEPLETION FOLLOWING

INDUCE A TRANSITORY REDUCTION ISCHEMIA AND REPERFUSION.

IN

MYOCARDIAL

CAPILLARY

Jesper H. Svendsen, Peter R. Hansen, Samir Ali, Ulrik Baandrup, Stig Haunso. Department of Medicine B, Division of Cardiology, Rigshospitalet, University of Copenhagen, Denmark. Neutrophils (PMN) appear to participate in the reperfusion injuty. Fifteen open chest dogs were randomized to treatment with a polyclonal rabbit antibody against canine PMN (anti-PMN, 5 mg.kg.‘) (n = 8) or control antibody (n = 7) and subjected to 40 min of LAD occlusion followed by reperfusion. Myocardial plasma flow and capillary extraction (E) for 99mTc-DTPA were measured by the single injection, residue detection method, and the corresponding capillary permeability-surface area product (PS; ml(lOOgmin)~i’) was calculated. Microcirculatory variables were measured before antibody infusion and 5 min after reperfusion. In the anti-PMN group a maximum reduction in blood-PMN to 20 % of baseline values was seen. Five min after start of reperfusion E was 78.3 + 11.3 % (mean 2 1 SEM) of baseline values in the anti-PMN group vs. 117.0 ? 6.3 % in the control group (p
O-17-5

INHIBITION THE RABBIT

OFNEUTROPHIL BY TRIMETAZlDlNE.

ACCUMULATION

INTO

ISCHAEMIC-REPERFUSED

MYOCARDRJM

IN

Frances M Williams, Kalbinder Tanda, Michelle Kus, Timothy J Williams. Department of Applied Pharmacology, National Heart & Lung Institute, London, England. The effect of trimetaxidine (2.5 mg/kg) on inflammation in the myocardium following ischaemia and repcrfusion was examined in the anaesthetixed rabbit. The drug or saline was administered i.v. 10 min prior to coronary artery occlusion. A 30 min period of ischaemia was followed by 3 hours of reperfusion. Neutrophil accumulation and plasma protein leakage were measured using “‘Inneutrophils and ‘ZsI-albumin respectively. The area at risk (AR) was 22+2 % of the left ventricle in controls and 26*2 % in the trimetazidine group (n=lO). In the control group the number of “‘Inneutrophils was significantly increased from 11519~1605/g in the normal zone (NZ) to 30591+6725/g in the AR (pCO.01). Trimetazidine markedly suppressed this accumulation of “‘Inneutrophils there being 7832+1117/g in the NZ and 12717*1958/g in the AR (n.s.). Oedema formation in the AR was not affected by treatment with trimetaxidine. The number of circulating “‘In-neutrophils/ml of blood did not differ in the two groups. Retention of “‘In-neutrophils in blood by nylon wool columns (ex vivo), under control conditions or in the presence of a stimulus (10A7M FMLP)

was also unaffected.

neutrophil

accumulation

The

mechanisms

underlying

O-17s6LACK

OF EVIDENCE TBAT TISSUE INFILTRATION POST-ISCHRMIC CELL DBATH Hermann If. Klein, Rainer M. Bohle, Sibylle Iieimberg , Dirk Gehrke, K. Nebendahl. Dept.

University The

reperfused C, n=E). ischemic determined

this inhibitory

effect

of ttimetazidine

have yet to be elucidated.

OF

NRUTROPHILS

Pith.

CAUSES

Stefanie

Lindert-

of Cardiology,

of Marburg, Fed. Rep. of Germany was ligated distally in 24 pigs for 45 min and was for 3 (group A, n=8), 24 (group B, n=8), or 72 h (group Infarct size was determined as ratio of infarcted to myocardium. Myocardial neutrophil infiltration was

LAD

by

histological

and

histochemical

of the three groups did not differ significantly 2096, group B 71.8 f 13%, group C 67.6 f 18%). similar infarct sizes, neutrophil infiltration significantly between 3 and 72 h of renerfusion. amounted to 4 f 2- (group neutrophil count/mm2 Bl and 10 f 7 (group C). These results do not neutrophil accumulation within the reperfused post-ischemic cell death. s.90

means.

Infarct

sizes

(group A 62.6 In contrast to differed highly Myocardial Al,

is9

f

70

(group

suggest that myocardium causes

+

on