Effect of Colchicine on Circulating and Myocardial Neutrophils and on Infarct Size in a Canine Model of Ischemia and Reperfusion

Abstract

Myocardial injury after ischemia/reperfusion has been attributed in part to the effects of neutrophils. We examined whether colchicine, a potent and rapid inhibitor of neutrophils, may reduce inflammatory leukocytosis, 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 intravenously, i.v.) group. Anesthetized open-chest dogs underwent 120-min coronary artery occlusion followed by 6-h reperfusion. Determinants of IS [area-at-risk (AAR) and collateral flow] and IS were measured in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex vivo production of reactive oxygen species by chemiluminescence. Myocardial localization and accumulation of neutrophils were histologically evaluated by independent observers. The number of circulating neutrophils (p < 0.01), neutrophil cytotoxicity (p < 0.05), and neutrophil myocardial accumulation after 6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV) peak rate of pressure increase was similar in both groups during ischemia /reperfusion. However, whereas collateral blood flow and AAR, the main determinants of IS, were similar 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 marked reduction of neutrophil toxicity and postischemic myocardial neutrophil accumulation, no myocardial protection could be detected in this dog model.