EFFECT OF DURATION OF ISCHEMIA ON REDUCTION OF MYOCARDIAL INFARCT SIZE BY INHIBITION OF NEUTROPHIL ACCUMULATION USING AN ANTI-CD18 MONOCLONAL-ANTIBODY

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.