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Caffeine Prevents Protection in Two Human Models of Ischemic Preconditioning

Niels P. Riksen, MD^_*,,_*, Zhigang Zhou, MD^_*, Wim J.G. Oyen, MD, PhD, Rogier Jaspers, MD, Bart P. Ramakers, MSc^_*, Rene M.H.J. Brouwer, MD, PhD, Otto C. Boerman, PhD, Neil Steinmetz, MD, PhD^||, Paul Smits, MD, PhD^_*, and Gerard A. Rongen, MD, PhD^_*,

^_* Pharmacology-Toxicology
Internal Medicine
Nuclear Medicine
Cardiothoracic Surgery, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
^|| North American Scientific, Theseus Imaging Division, Boston, Massachusetts

View larger version (8K): [in a new window]   Figure 1 Schematic representation of the experimental protocol of the 2 randomized double-blinded in vivo studies. "IP" (ischemic preconditioning) indicates the 10-min period of ischemia (without concomitant exercise); "Isch Ex" (ischemic exercise) indicates the 10-min period of ischemia with isometric handgripping.

View larger version (14K): [in a new window]   Figure 2 Annexin A5 targeting in the thenar muscle at 1 (open bars) and 4 (solid bars) h after reperfusion in the different groups (expressed as percent difference between experimental and control hand). The p values indicate differences between groups as assessed by repeated measures analysis of covariance with time (t = 1 and t = 4 h after reperfusion) as within-subject factor, group (as indicated on the x-axis) as between-subject factor, and workload as covariate. IP = ischemic preconditioning; Isch Ex = ischemic exercise.

View larger version (123K): [in a new window]   Figure 3 Representative scintigraphic images of the experimental and control hands at 1 and 4 h after reperfusion in preconditioned subjects pre-treated with caffeine (A) and saline (B). Annexin targeting was 2% and 3% after saline administration (saline-ischemic preconditioning-ischemic exercise) and 19% and 27% after caffeine administration (caffeine-ischemic preconditioning-ischemic exercise) at 1 and 4 h, respectively.

View larger version (13K): [in a new window]   Figure 4 The course of contractile force (expressed as percentage of baseline force) in time in control trabeculae (n = 17) with (open squares) and without (open circles) preconditioning and in caffeine pre-treated trabeculae (n = 13) with (filled squares) and without (filled circles) preconditioning. *p = 0.008 for the effect of preconditioning on post-ischemic recovery of contractile force in the saline group. For the sake of clarity, the symbols representing the non-preconditioned groups are slight shifted to the right. IP = ischemic preconditioning.