Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

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%...