Fm. Williams et al., EFFECT OF DURATION OF ISCHEMIA ON REDUCTION OF MYOCARDIAL INFARCT SIZE BY INHIBITION OF NEUTROPHIL ACCUMULATION USING AN ANTI-CD18 MONOCLONAL-ANTIBODY, British Journal of Pharmacology, 111(4), 1994, pp. 1123-1128
1 Neutrophil accumulation is a characteristic feature of the inflammat
ory response in myocardial tissue which has undergone a period of isch
aemia. The aim of this study was to examine whether inhibition of myoc
ardial neutrophil infiltration, using an antibody to the CD18 leukocyt
e adhesion molecule, was effective in reducing infarct size in anaesth
etized rabbits. 2 Anaesthetized rabbits underwent coronary artery occl
usion (CAO) for periods of 30 or 45 min followed by reperfusion for 3
h. Animals were treated intravenously 10 min prior to reperfusion with
IB4, a monoclonal antibody to CD18 (1 mg kg-1) or saline (1 ml kg-1).
In one group undergoing 45 min CAO, a control antibody, OKMI (1 mg kg
-1) was given. 3 Following either 30 or 45 min of CAO, administration
of IB4 resulted in a < 75% inhibition in neutrophil accumulation in th
e area at risk myocardium (AR) compared with control animals. 4 With t
he 30 min occlusion period, IB4 significantly reduced myocardial infar
ct size, 27.2 +/- 3.2% vs 67.4 +/- 5.6% in the saline control group (n
= 5 P < 0.01). In contrast, IB4 did not reduce infarct size following
a 45 min period of ischaemia. 5 In the same animals administration of
IB4 significantly inhibited oedema formation in skin elicited by intr
adermal administration of the neutrophil chemoattractant f-Met-Leu-Phe
, but had no effect on coronary microvascular plasma protein leakage i
n the AR. 6 Our results indicate that infiltrating neutrophils exacerb
ate tissue injury following a relatively short, 30 min period of myoca
rdial ischaemia in the rabbit. However, protection with IB4 was no lon
ger seen if the period of CAO was extended to 45 min. The results in t
his model suggest neutrophils are not a major determinant of tissue in
jury following more than a very short period of ischaemia.