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relating to or affected by ischemia (同)ischaemic

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/12 15:10:24」(JST)

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Ischemic preconditioning (IPC) is an experimental technique^{[citation needed]} for producing resistance to the loss of blood supply, and thus oxygen, to tissues of many types. In the heart, IPC is an intrinsic process whereby repeated short episodes of 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 min 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.^[1] The exact molecular pathways behind this phenomenon have yet to be fully understood.

Background

If the blood supply to an organ or a tissue is impaired 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.

The protective effect which is imparted by IPC has two windows of protection. The first, lasts between 4–6 hours ^[2] and has been named classical or early preconditioning. The second window begins at 24 hours lasting up to 72 hours post the ischaemia and reperfusion stimulus.^[3]

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 mitochondrion.

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.

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. Such injury would occur when a patient has an acute myocardial infarct followed by reperfusion by either percutaneous coronary intervention or thrombolysis.

Early Preconditioning

Is thought to be stimulated by local action of adenosine, opiates and bradykinin which are all endogenously released by ischemic cells. The presence of each substance is not required but the protection is more potent if they are. They activate G-protein coupled pathways, which carries a protective signal to an end-effector. There have been many suggestions to what this might be, the sarcolemmal ATP-sensitive potassium channel, the mitochondrial ATP-sensitive potassium channel, the mitochondrial permeability transition pore, reactive oxygen species generation, chloride channels, the inward rectifier potassium channel and connexon 43 related channels.

Impairment of Preconditioning

It has also been shown that the protective effect of IPC is suppressed by pathological conditions such as hypercholesterolemia, hyperglycemia, hypertension, cardiac hypertrophy, aging, obesity and hyperhomocysteinemia.

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:

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 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^{[citation needed]}, 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.

References

Citations

^ Murry, CE; Jennings, RB, Reimer, KA (1986 Nov). "Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.". Circulation 74 (5): 1124–36. PMID 3769170.
^ Rodrigo, GC; Samani, NJ (2008 Jan). "Ischemic preconditioning of the whole heart confers protection on subsequently isolated ventricular myocytes.". American journal of physiology. Heart and circulatory physiology 294 (1): H524-31. PMID 17965281.
^ Das, Manika; Das, Dipak K. (31 March 2008). "Molecular mechanism of preconditioning". IUBMB Life 60 (4): 199–203. doi:10.1002/iub.31. PMID 18344203.

Bibliography

Gross GJ (2003). "Role of opioids in acute and delayed preconditioning". J. Mol. Cell. Cardiol. 35 (7): 709–18. doi:10.1016/S0022-2828(03)00135-4. PMID 12818560.
Marmor M, Penn A, Widmer K, Levin RI, Maslansky R (2004). "Coronary artery disease and opioid use". Am. J. Cardiol. 93 (10): 1295–7. doi:10.1016/j.amjcard.2004.01.072. PMID 15135709.

UpToDate Contents

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1. 虚血プレコンディショニングの定義および病因 definition and pathogenesis of ischemic preconditioning
2. 虚血プレコンディショニングの臨床的意義 clinical implications of ischemic preconditioning
3. 糖尿病の治療におけるスルホニル尿素およびメグリチニド sulfonylureas and meglitinides in the treatment of diabetes mellitus
4. 経皮的冠動脈形成術後の周術期心筋梗塞 periprocedural myocardial infarction following percutaneous coronary intervention
5. 心臓の虚血性再潅流障害 ischemic reperfusion injury of the heart

English Journal

Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.

Shafiq M1, Jung Y1, Kim SH2.
Biomaterials.Biomaterials.2016 Jun;90:85-115. doi: 10.1016/j.biomaterials.2016.03.020. Epub 2016 Mar 15.
Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transpla
PMID 27016619

Lack of MG53 in human heart precludes utility as a biomarker of myocardial injury or endogenous cardioprotective factor.

Lemckert FA1, Bournazos A2, Eckert DM2, Kenzler M2, Hawkes JM3, Butler TL3, Ceely B4, North KN5, Winlaw DS4, Egan JR4, Cooper ST5.
Cardiovascular research.Cardiovasc Res.2016 May 15;110(2):178-87. doi: 10.1093/cvr/cvw017. Epub 2016 Jan 19.
AIMS: Mitsugumin-53 (MG53/TRIM72) is an E3-ubiquitin ligase that rapidly accumulates at sites of membrane injury and plays an important role in membrane repair of skeletal and cardiac muscle. MG53 has been implicated in cardiac ischaemia-reperfusion injury, and serum MG53 provides a biomarker of ske
PMID 26790476

Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning.

Wojtovich AP1, Smith CO, Urciuoli WR, Wang YT, Xia XM, Brookes PS, Nehrke K.
Anesthesiology.Anesthesiology.2016 May;124(5):1065-76. doi: 10.1097/ALN.0000000000001046.
BACKGROUND: Anesthetic preconditioning (APC) is a clinically important phenomenon in which volatile anesthetics (VAs) protect tissues such as heart against ischemic injury. The mechanism of APC is thought to involve K channels encoded by the Slo gene family, and the authors showed previously that sl
PMID 26845140

Japanese Journal

Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in rats: the roles of phosphatidylinositol 3-kinase and nitric oxide

Toyoda Tomomi,Tosaka Shinya,Tosaka Reiko,Maekawa Takuji,Cho Sungsam,Eguchi Susumu,Nakashima Masahiro,Sumikawa Koji
Journal of Surgical Research 186(1), 446-451, 2014-01
… Background Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR) injury. … Milrinone, a phosphodiesterase 3 inhibitor, has been reported to exhibit preconditioning properties against hepatic IR injury; …
NAID 120005365977

細胞レベルからみた外科的心筋保護法の現況と次世代への展望

丸山雄二,Chambers David J,別所竜蔵,藤井正大,仁科大,新田隆,落雅美
日本心臓血管外科学会雑誌 43(5), 239-253, 2014
… "ischemic preconditioning"と"ischemic postconditioning"という概念が注目されている．しかしながら，心臓手術におけるこれらの付加的心筋保護効果は確立されておらず，いずれも複数回の大動脈遮断による脳塞栓症というリスクを伴うため，すべての心臓手術に適用するには難しいかもしれない．一方，虚血前または再灌流時に薬剤を使用する"pharmacological preconditioning" …
NAID 130004700586

Hypoxic Preconditioning Increases Survival of Cardiac Progenitor Cells via the Pim-1 Kinase-Mediated Anti-Apoptotic Effect

Hu Shengda,Yan Gaoliang,Xu Hongzeng [他],He Wei,Liu Zhiyong,Ma Genshan
Circulation Journal 78(3), 724-731, 2014
… Background: Stem cells transplanted to the ischemic myocardium usually encounter massive cell death within a few days after transplantation, and hypoxic preconditioning (HPC) is currently used as a strategy to prepare stem cells for increased survival and engraftment in the heart. …
NAID 130003382258