Ischemic preconditioning

Editor-in-Chief: Juan A. Sanchez MD MPA, Chairman, The Stanley J. Dudrick Department of Surgery, Saint Mary's Hospital, Waterbury, CT

Overview
Ischemic preconditioning (IPC) is an experimental technique for producing resistance to the loss of blood supply and, thus oxygen, to tissues of many types. Keith Reimer MD, PhD first described this procedure in 1986.

Background
If the blood supply to an organ or a tissue is halted for a short time (usually less than five minutes) and then restored two or more times so that blood flow is resumed the downstream cells of the tissue or the organ are robustly protected from a final ischemic insult when the blood supply is cut off entirely and permanently.

In an experimental setting if the left anterior descending coronary artery of the animal is ligated the downstream cardiac cellular mass is infarcted and will be injured and then die. If, on the other hand the tissue is subjected to IPC the downstream cellular mass will sustain only minimal to modest damage. IPC protects the tissue by initiating a cascade of biochemical events that allows for an up-regulation of the energetics of the tissue. The locus of this phenomenon is the intracellular organelle, the mitochondrium.

Investigations of various exogenous circulating ligands such as the delta active opiates and opioids simulate the phenomenon of IPC thus protecting the downstream tissues without the IPC intermittent ligating procedure.

Application
The only group of humans who are chronically exposed to an opioid with delta activity are methadone maintained patients treated for heroin dependence and addiction. These patients have a coronary risk profile greater than the general population:
 * 1) 90% smoke. In the general population in the USA ~25% smoke.
 * 2) Heart Healthy living i.e. attention to lipid control is less frequent than in the general population
 * 3) ~25% of the patients in Methadone Maintenance Programs use the highly ischemogenic cocaine one or more times a year. In the general population in the USA less than 1% are reported to do so.

Preliminary and as yet unpublished surveys of the methadone treated population point to a high degree of protection from myocardial ischemic events. The one published study, an autopsy series from the Office of the Chief Medical Examiner of the City of New York demonstrated significantly less evidence for coronary occlusive disease. Simulation of IPC with methadone could not be evaluated in this post mortem investigation.