Ischemic preconditioning (IPC) is an experimental technique
ischaemia protect the myocardium against a subsequent ischaemic insult. It was first identified in 1986 by Murry et al. This group exposed anesthetised open-chest dogs to four periods of 5 minute coronary artery occlusions followed by a 5-minute period of reperfusion before the onset of a 40-minute sustained occlusion of the coronary artery. The control animals had no such period of “ischaemic preconditioning” and had much larger infarct sizes compared with the dogs that did.[2]
The exact molecular pathways behind this phenomenon have yet to be fully understood.
Background
Ischemic preconditioning of the heart (B) provides functional recovery of the heart contractile activity at reperfusion
If the blood supply to an
ischemic insult when the blood supply is cut off entirely and permanently.[citation needed
]
The protective effect which is imparted by IPC has two windows of protection. The first lasts between 4–6 hours[3] and has been named classical or early preconditioning. The second window begins at 24 hours and lasts up to 72 hours after the ischaemia and reperfusion stimulus.[4]
In an experimental setting if the
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 mitochondrion.[citation needed
]
Investigations of various exogenous circulating ligands such as the delta active
opioids
simulate the phenomenon of IPC thus protecting the downstream tissues without the IPC intermittent ligating procedure.
Methods to either mimic or elicit IPC have been attempted in clinical practice in the area of coronary heart disease in an attempt to limit the injury caused to the heart via ischemia and reperfusion injury.[5] Such injury would occur when a patient has an acute myocardial infarct followed by reperfusion by either percutaneous coronary intervention or thrombolysis.
Early Preconditioning
Early preconditioning is thought to be stimulated by local action of
The only group of humans who are chronically exposed to an opioid with delta activity are
opioid addiction
. These patients have a coronary risk profile greater than the general population:
90% smoke. In the general population in the USA ~25% smoke.
Heart Healthy living i.e. attention to lipid control is less frequent than in the general population
~25% of the patients in Methadone Maintenance Programs use cocaine, which is highly ischemogenic, one or more times a year. Less than 1% of the USA's general population is 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,[
post mortem
investigation.
Remote pre- and post-conditioning
Rather than blocking a
coronary artery, similar results have been seen by blocking the brachial artery using a blood pressure cuff prior to surgery.[6] Some research also suggests that ischemic conditioning is also beneficial following a stroke,[7][8] chronic cerebral hypoperfusion,[9] or heart attack.[10]
