Colchicine inhibits isoflurane-induced preconditioning

Background: When administered before prolonged myocardial ischemia and repe rfusion, isoflurane exerts potent cardioprotective effects similar to those inferred by ischemic preconditioning. To determine whether an intact cytos keleton is critically important in isoflurane-induced preconditioning, the authors used a rabbit model in which isoflurane-induced myocardial precondi tioning decreases myocardial infarct size (18) substantially. In this model , the authors tested whether the microtubule depolymerizing agent, colchici ne, would inhibit isoflurane-induced myocardial preconditioning. Methods: Myocardial IS was measured in four groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion foll owed by 3 h of reperfusion, Groups differed only in the pretreatments given , and only the control group received no pretreatment An isoflurane-precond itioned group was pretreated with 15 min of end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-colchicine group was administer ed 2 mg/kg colchicine intravenously before isoflurane pretreatment. A colch icine-control group was administered 2 mg/kg colchicine but no isoflurane p retreatment. Myocardial IS and area at risk (AR) were defined by staining. Data were analyzed by analysis of variance or covariance. Results: Infarct size, expressed as a percentage of AR (IS:AR) was 33.6% +/ - 8.8% (SD) in the control group. Isoflurane preexposure reduced myocardial IS:AR significantly, to 11.8% +/- 9.1% Colchicine pretreatment eliminated the preconditioning. like effect of isoflurane (IS:AR = 32.6% +/- 8.7%). Co lchicine alone did not alter IS (IS:AR = 27.6% +/- 7.1%; P = not significan t). Conclusions: Colchicine abolished the preconditioning effect of isoflurane but did not increase IS when administered alone. An intact microtubular cyt oskeleton is critically important in the process of volatile anesthetic-ind uced preconditioning.