The Optimal Strategy of Noninvasive Limb Ischemic Preconditioning for Protecting Heart Against Ischemia-Reperfusion Injury in Rats

Abstract

Limb ischemic preconditioning (LIPC) induced by prior brief periods of ischemia-reperfusion (I/R) to a limb is a simple and convenient strategy to protect the heart from I/R injury. However, the optimal strategy is unknown. Therefore, the present study was conducted to test the most effective method of LIPC for clinical applications. Male Wistar rats were randomized into the following groups: control groups, consecutive LIPC groups, intermittent LIPC groups. The control groups, including the sham operation group, the ischemia-reperfusion (I/R)-control group, the myocardial ischemic preconditioning (MIPC) group, the femoral artery ischemic preconditioning (FAIP) group; the consecutive LIPC groups, including continuously using for 1 d, 3 d, and 7 d groups. Each group was tested on the first, third, and fifth d after LIPC; intermittent LIPC groups, including 1-d LIPC + 1-d interval group, 1-d LIPC + 2-d interval group, 3-d LIPC + 3-d interval group, 3-d LIPC + 5-d interval group. Left ventricular function, incidence of ventricular arrhythmia, and ST-segment were measured during I/R. Myocardial infarct size, creatine kinase isoenzyme MB (CK-MB), and cardiac troponins I (cTnI) were determined at the end of experiment. Compared with the I/R-controls, the MIPC, FAIP, continuous LIPC for 3 and 7 d and 1-d LIPC + 1-d interval groups showed amelioration of ventricular arrhythmia, improved left ventricular function, lower ST-segment elevation, reduced myocardial infarct size, decreased CK-MB, and cTnI activity. The protective effects of LIPC persisted for 72 h. Our results suggest that a 1-d LIPC + 1-d interval provides optimal cardioprotection from I/R.