Effect of duration of ischaemia on reduction of myocardial infarct size by inhibition of neutrophil accumulation using an anti-CD18 monoclonal antibody.

Abstract

1. Neutrophil accumulation is a characteristic feature of the inflammatory response in myocardial tissue which has undergone a period of ischaemia. The aim of this study was to examine whether inhibition of myocardial neutrophil infiltration, using an antibody to the CD18 leukocyte adhesion molecule, was effective in reducing infarct size in anaesthetized rabbits. 2. Anaesthetized rabbits underwent coronary artery occlusion (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 the area at risk myocardium (AR) compared with control animals. 4. With the 30 min occlusion period, IB4 significantly reduced myocardial infarct 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 intradermal administration of the neutrophil chemoattractant f-Met-Leu-Phe, but had no effect on coronary microvascular plasma protein leakage in the AR. 6. Our results indicate that infiltrating neutrophils exacerbate tissue injury following a relatively short, 30 min period of myocardial ischaemia in the rabbit. However, protection with IB4 was no longer seen if the period of CAO was extended to 45 min. The results in this model suggest neutrophils are not a major determinant of tissue injury following more than a very short period of ischaemia.