Ischemic preconditioning-induced microcirculatory protection appears to be a systemic rather than a local phenomenon. This protection induced by remote ischemic preconditioning (RIPC) may be attributed to a humoral rather than a neuronal mechanism.
An innervated (Inn, Groups 1 and 4) or denervated (Den, Groups 2 and 3) and vascular isolated right cremaster of the rat was prepared. Left femoral vessels were clamped (Groups 1, 2, and 4) for 45 min or unclamped (Group 3) as a control. After 2 hr of reperfusion in the left lower extremity, 4 hr of ischemia in the right cremaster was applied in Groups 1, 2, and 3. However, in Group 4, 4 hr of ischemia in the cremaster muscle was instituted before reperfusion of the left femoral artery was begun. Microcirculatory responses, including terminal arteriole diameter, capillary perfusion, and endothelium function were evaluated. Four groups (six rats per group) were designed: Group 1: RIPC (Inn); Group 2: RIPC (Den); Group 3: sham RIPC (Den); and Group 4: fake RIPC (Inn).
Ischemia of 45 min followed by 2 hr of reperfusion in the left lower extremity of the rat induced a significant microvascular protection against subsequent 4-hr ischemia in both innervated and denervated cremasters. This microvascular protection at a distance was lost in sham RIPC and in fake RIPC groups.
The results demonstrated that remote protection induced by ischemic preconditioning is a systemic phenomenon and due to a humoral mechanism.
KEYWORDS
Ischemic preconditioning - ischemia reperfusion - microcirculation
REFERENCES
-
1
Murry C E, Jennings R B, Reimer K A.
Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.
Circulation.
1986;
74
1124-1136
-
2
Marber M S, Latchman D S, Walker J M, Yellon D M.
Cardiac stress protein elevation 24 hours after brief ischemia or late stress is associated with resistance to myocardial infarction.
Circulation.
1993;
88
1264-1272
-
3
Yellon D M, Baxter G F, Garcia-Dorado D, Heusch, Sumeray M S.
Ischemic preconditionig: present and future directions.
Cardiovasc Res.
1998;
37
21-33
-
4
Przyklenk K, Bauer B, Ovize M, Kloner R A, Whittaker P.
Regional ischemic “preconditioning” protects remote virgin myocardium from subsequent sustained coronary occlusion.
Circulation.
1993;
87
893-899
-
5
Guo B C, Schoemaker R G, van den Doel M A, Duncker D J, Verdouw P D.
Myocardial protection by brief ischemia in noncardiac tissue.
Circulation.
1996;
94
2193-2200
-
6
Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B.
Limb ischemia preconditions the heart against reperfusion tachyarrhythmia.
Am J Physiol.
1997;
273 (Heart Circ Physiol 42)
H1707-H1712
-
7
Birnbaum Y, Hale S L, Kloner R A.
Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit.
Circulation.
1997;
96
1641-1646
-
8
Dickson E W, Lorbar M, Porcaro W A et al..
Rabbit heart can be “preconditioned” via transfer of coronary effluent.
Am J Physiol.
1999;
277 (Heart Circ. Physiol. 46)
H2451-H2457
-
9
Takaoka A, Nakae I, Mitsunami K et al..
Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of “remote preconditioning.”
J Am Coll Cardiol.
1999;
33
556-564
-
10
Verdouw P D, Gho B CG, Koning M MG, Schoemaker R G, Duncker D J.
Cardioprotection by ischemic and nonischemic myocardial stress and ischemia in remote organs. Implications for the concept of ischemic preconditioning.
Ann N Y Acad Sci.
1996;
30;793
27-42
-
11
Schoemaker R G, van Heijningen C L.
Bradykinin mediates cardiac preconditioning at a distance.
Am J Physiol Heart Circ Physiol.
2000;
278
H1571-H1576
-
12
Wolfrum S, Schneifer K, Heidbreder M, Nienstedt J, Dominiak P, Dendorfer A.
Remote preconditioning protects the heart by activating myocardial PKCepsilon-isform.
Cardiovasc Res.
2002;
55
583-589
-
13
Gunaydin B, Cakici I, Soncul H et al..
Does remote organ ischemia trigger cardiac preconditioning during coronary artery surgery?.
Pharmacol Res.
2000;
41
493-496
-
14
Dickson E W, Tubbs R J, Porcaro W A et al..
Myocardial preconditioning factors evoke mesenteric ischemic tolerance via opioid receptors and K(ATP) channels.
Am J Physiol Heart Circ Physiol.
2002;
283
H22-H28
-
15
Harkin D W, Barros D'Sa A A, McCallion K, Hoper M, Campbell F C.
Ischemic preconditioning before lower limb ischemia-reperfusion protects against acute lung injury.
J Vasc Surg.
2002;
35
1264-1273
-
16
Petrishchev N N, Vlasov T D, Sipovsky V G, Kurapeev D I, Galagudza M M.
Does nitric oxide generation contribute to the mechanism of remote ischemic preconditioning?.
Pathophysiology.
2001;
7
271-274
-
17
Weinbrenner C, Nelles M, Herzog N, Sarvary L, Strasser R.
Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infraction: a newly identified non-neuronal but PKC-dependent pathway.
Cardiovasc Res.
2002;
55
590-601
-
18
Wang W Z, Anderson G L, Firrell J C.
Arteriole constriction following ischemia in denervated skeletal muscle.
J Reconstr Microsurg.
1995;
11
99-106
-
19
Wang W Z, Anderson G, Acland R D, Barker J.
Endothelin-1 does not contribute to ischemia/reperfusion-induced vasoconstriction in skeletal muscle.
J Reconstr Microsurg.
1997;
13
439-447
-
20
Wang W Z, Anderson G, Fleming J T et al..
Lack of nitric oxide contributes to vasospasm during ischemia/reperfusion injury.
Plast Reconstr Surg.
1997;
99
1099-1108
-
21
Wang W Z, Guo S Z, Tsai T M, Anderson G L, Miller F N.
Platelet-activating factor contributes to postischemic vasospasm.
J Surg Res.
2000;
89
139-146
-
22
Wang W Z, Anderson G L, Maldonado C, Barker J.
Attenuation of vasospasm and capillary no-reflow by ischemic preconditioning in skeletal muscle.
Microsurgery.
1996;
17
324-329
-
23
Wang W Z, Anderson G L, Firrell J C, Tsai T M.
Ischemic preconditioning versus intermittent reperfusion to improve blood flow to a vascular isolated skeletal muscle flap of rats.
J Trauma.
1998;
45
953-959
-
24
Wang W Z, Tsai T M, Anderson G L.
Late preconditioning protection is evident in the microcirculation of denervated skeletal muscle.
J Orthope Res.
1999;
17
571-577
-
25
Wang W Z, Guo S Z, Tsai T M, Anderson G L, Miller F N.
The initiation of microvascular protection by nitric oxide in the late preconditioning.
J Reconstr Microsurg.
2000;
16
621-628
-
26
Wang W Z, Anderson G L.
Intervention approaches against I/R-induced arterial insufficiency in reconstructive microsurgery.
Hand Clin.
2001;
17
357-369
-
27
Wang W Z, Guo S Z, Tsai T M, Anderson G L, Miller F N.
The initiating factors of late preconditioning in the microcirculation of skeletal muscle.
J Surg Res.
2001;
99
92-99
-
28
Wang W Z, Stepheson L L, Anderson G L, Miller F N, Khiabani K T, Zamboni W A.
Role of PKC in microvascular protection induced by late preconditioning.
J Surg Res..
2002;
106
166-172
-
29
Wang W Z, Jones S, Stepheson L L et al..
Microvascular protection induced by late preconditioning abolished in STZ-induced diabetic rats.
J Reconstr Microsurg.
2002;
18
389-396
-
30
Menger M D, Rucker M, Vollmar B.
Capillary dysfunction in striated muscle ischemia/reperfusion: on the mechanisms of capillary “no-reflow”.
Shock.
1997;
8
2-7
-
31 Addison P D, Ashrafpour H, LaScala G, Forrest C R, Neligan P C, Pang C Y. Remote ischemic preconditioning of the porcine latissimus dorsi flap protects against subsequent flap ischemia. 47th Annual Meeting, Plastic Surgery Research Council 2002: 102
Wei Z WangM.D.
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