Decreased effectiveness of ischemic heart preconditioning in the state of chronic inflammation.

There is growing evidence, that beneficial effects of ischemic heart preconditioning (IPC) may be lost or limited due to diabetes, hyperlipidemia, hypertension, atherosclerosis, heart failure and senility. It is plausible, that these conditions interfere with the biochemical pathways underlying the IPC response, but the detailed explanation is not clear. Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), monocyte chemotactic protein-1 (MCP-1), histamine and many other agents used in a single dose before prolonged ischemia mimic IPC. However prolonged exposure to preconditioning mimetics leads to tolerance (tachyphylaxis). In the state of such tolerance ischemic preconditioning is no longer protective. Studies suggest that diabetes, hyperlipidemia, hypertension, atherosclerosis, heart failure and older age are accompanied by increased plasma levels of pro-inflammatory cytokines, MCP-1 and other inflammatory mediators. Therefore, we raised the hypothesis, that the reported lack of benefits of IPC in the listed states may be due to tolerance to IPC developed during prolonged exposure of the myocardium to preconditioning mimetics.