Dual effect of pre-ischemic administration of TNF-alpha on myocardial infarct size

Abstract

Tumour necrosis factor-α is a cytokine released during myocardial infarction. According to the literature, the effect of TNFα on myocardial infarction is controversial, especially when administered before the ischemic period. The deleterious effects of TNFα seem to be related to the triggering of apoptosis. This study has been designed to determine if different doses of TNFα, administered before the ischemic period, have the same effect on infarct size and on activation of caspase-3 and -8, two enzymes involved in apoptosis. Four groups, using a porcine model of myocardial infarction, have been used: placebo and TNFα (0.1 µg/kg; 1 µg/kg and 3 µg/kg). All administered 15 minutes before a 50 minutes occlusion of the left anterior descending artery. Myocardial infarct size has been determined at 3 hours of reperfusion. In a subgroup of animals, reperfusion period has been limited to 15 min to determine the activity of caspase-3 and -8 by spectrofluorometry. Results indicated that infarct size is significantly smaller in groups 0.1 µg/kg and 1 µg/ kg as compared to the placebo group. In contrast, the 3 µg/kg group presented an infarct size similar to the placebo group. Activity of caspase-3 and -8 is reduced in the ischemic region in groups 0.1 and 1 µg/ kg as compared to the placebo group whereas activity in the 3 µg/kg group was similar to the placebo. The results obtained indicated that a low dose of TNFα administered before the ischemic period reduces infarct size, whereas the cardioprotection is lost with the high dose.