EFFECT OF COLCHICINE ON CIRCULATING AND MYOCARDIAL NEUTROPHILS AND ONINFARCT SIZE IN A CANINE MODEL OF ISCHEMIA AND REPERFUSION

Myocardial injury after ischemia/reperfusion has been attributed in pa rt to the effects of neutrophils. We examined whether colchicine, a po tent and rapid inhibitor of neutrophils, may reduce inflammatory leuko cytosis, prevent postischemic myocardial neutrophil accumulation, and reduce infarct size (IS). Twenty-four dogs were randomized to either a control (saline administration) or a colchicine (1 mg/kg intravenousl y, i.v.) group. Anesthetized open-chest dogs underwent 120-min coronar y artery occlusion followed by 6-h reperfusion. Determinants of IS [ar ea-at-risk (AAR) and collateral flow] and IS were measured in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex v ivo production of reactive oxygen species by chemiluminescence. Myocar dial localization and accumulation of neutrophils were histologically evaluated by independent observers. The number of circulating neutroph ils (p < 0.01), neutrophil cytotoxicity (p < 0.05), and neutrophil myo cardial accumulation after 6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV) peak rate of pressure increase wa s similar in both groups during ischemia/reperfusion. However, whereas collateral blood flow and AAR, the main determinants of IS, were simi lar in control and treated dogs, there was no reduction in IS: 37.1 +/ - 7% of AAR in controls and 37.4 +/- 8% in treated dogs. Despite marke d reduction of neutrophil toxicity and postischemic myocardial neutrop hil accumulation, no myocardial protection could be detected in this d og model.