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Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways

Xi-Ming Yang, MD, PhD^*, J. Bradley Proctor, BS^*, Lin Cui, MD^*, Thomas Krieg, MD^*, James M. Downey, PhD^* and Michael V. Cohen, MD, FACC^*,,*

^* Physiology
Medicine, University of South Alabama, College of Medicine, Mobile, Alabama, USA

View larger version (21K): [in a new window]   Figure 1 Experimental protocols for animal groups exposed to 30-min coronary artery occlusions. Glib = glibenclamide; 5-HD = 5-hydroxydecanoate; L-NAME = N-nitro-L-arginine methyl ester; PC = ischemic preconditioning.

View larger version (12K): [in a new window]   Figure 2 Experimental protocols for animal groups exposed to 45-min coronary artery occlusions. PC = ischemic preconditioning.

View larger version (22K): [in a new window]   Figure 3 Infarct size in in situ rabbit hearts. All animals had a 30-min coronary occlusion and 3-h reperfusion. Open circles represent individual experiments, closed circles depict group means with SEM. Both four and six immediate postconditioning cycles protected ischemic hearts, whereas delayed postconditioning elicited no protection. PD98059 did not block the protective effect of ischemic preconditioning. *p < 0.05 versus control.

View larger version (21K): [in a new window]   Figure 4 Infarct size in in situ rabbit hearts. All animals had a 30-min coronary occlusion and 3-h reperfusion. Open circles represent individual experiments, closed circles depict group means with SEM. Multiple cycles of immediate postconditioning limited infarct size, whereas glibenclamide (Glib), 5-hydroxydecanoate (5-HD), PD98059, and N-nitro-L-arginine methyl ester (L-NAME) blocked their protection. The tool drugs alone had no effect. *p < 0.05 versus other groups.

View larger version (28K): [in a new window]   Figure 5 Infarct size plotted against risk zone volume for control hearts and hearts with four cycles of postconditioning alone or after treatment with either PD98059, glibenclamide (Glib), N-nitro-L-arginine methyl ester (L-NAME), or 5-hydroxydecanoate (5-HD). Regression lines for the control group and postconditioned hearts treated with PD98059, Glib, L-NAME, or 5-HD were significantly different from that for hearts subjected only to postconditioning (p < 0.001).

View larger version (13K): [in a new window]   Figure 6 Infarct size in in situ rabbit hearts. All animals had a 45-min coronary occlusion and 3-h reperfusion. Open circles represent individual experiments, closed circles depict group means with SEM. Four postconditioning cycles resulted in significant salvage. A single preconditioning (PC) cycle of 5-min occlusion/10-min reperfusion before the 45-min ischemia also was protective. The combination of ischemic postconditioning and preconditioning resulted in even greater protection than either alone. *p < 0.05 versus control; **p < 0.05 versus PC and four cycles.