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Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Due to overlapping mechanisms this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term GTN treatment modifies the protection by RIC in rat myocardium and human endothelium. We studied infarct size (IS) in rat hearts subjected to global ischemia-reperfusion (I/R) in vitro and endothelial function in healthy volunteers subjected to I/R of the upper arm. In addition to allocated treatment, rats were co-administered with reactive oxygen species (ROS) or nitric oxide (NO) scavengers. Rats and humans were randomized to: 1) control, 2) RIC, 3) GTN, 4) GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN treatment for 7 consecutive days, applied s.c. or 2 hours daily transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18{plus minus}12%, p=0.007) and (15{plus minus}5%, p=0.002) compared to control (35{plus minus}13%). RIC and long-term GTN treatment in combination did not reduce IS (29{plus minus}12%, p=0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and long-term GTN treatment. In humans, I/R reduced endothelial function (p=0.01 vs. baseline). Separately, RIC and long-term GTN prevented the reduction in endothelial function caused by I/R; given in combination, prevention was lost. RIC and long-term GTN treatment both protect against rat myocardial and human endothelial I/R injury through ROS and NO dependent mechanisms. However, when given in combination, RIC and long-term GTN treatment fail to confer protection.

Original publication




Journal article


Am J Physiol Heart Circ Physiol

Publication Date



Cardioprotection, Endothelial function, Glyceryl trinitrate, Ischemic preconditioning, Remote ischemic conditioning