Abstract
It is still unknown whether remote ischemic preconditioning is mediated by a humoral or a neurogenic mechanism from the preconditioning to the preconditioned tissue. The purpose of the following study was to identify a possible humoral trigger of ischemic myocardial preconditioning and remote renal preconditioning. Open chest rats were subjected to a coronary artery occlusion period of 45 min followed by 2 h of reperfusion (Control animals; n = 6). The coronary preconditioned group (IPC, n = 6) was subjected to a preceding preconditioning period of 5 min coronary artery occlusion followed by 5 min of reperfusion, repeated three times. The renal preconditioned group (IPR, n = 6) was subjected to a preceding renal artery occlusion period of 10 min followed by 20 min of reperfusion. Area at risk (AAR) and infarcted area (IA) were determined at the end of each protocol. Blood samples were taken at the end of the preconditioning protocols from parallel experiments for proteomic analysis using two–dimensional gel electrophoresis (2-DE), matrix assisted laser desorption and ionization—time of flight—mass spectrometry (MALDI–TOF–MS), and liquid chromatography—electrospray ionization—tandem mass spectrometry (nanoLC–ESI–MS/MS). IA/AAR was 87.8 ± 10.7% in the control group. IPC and IPR signi.cantly reduced IA/AAR (58.2 ± 9.3% and 56.9 ± 9.0%, p < 0.001). Proteomic analyses detected four protein spots which were either up– (n = 3) or down–regulated in the preconditioned groups vs. the control group. The three up–regulated protein spots were identi.ed as albumin fragments, whereas the downregulated spot was identified as liver regeneration–related protein (LRRG03). Interestingly, albumin modification by brief ischemia has been recently shown and evaluated for the clinical diagnosis of sublethal myocardial ischemia. However, no differentially abundant proteins which possess a known signaling function could be found. Hence, though there is a differential protein expression in blood following IPC and IPR, our data are not in favor of a humoral mediator of remote preconditioning with a molecular weight of more than 8 kDa. Our results rather suggest either a neurogenic pathway or a mediator smaller than 8 kDa.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Aitchison KA, Baxter GF, Awan MM, Smith RM, Yellon DM, Opie LH (2000) Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning. Basic Res Cardiol 95:1–10
Bar Or D, Winkler JV, Vanbenthuysen K, Harris L, Lau E, Hetzel FW (2001) Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I. Am Heart J 141:985–991
Birnbaum Y, Hale SL, Kloner RA (1997) 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 96:1641–1646
Chien GL, Mohtadi K, Wolff RA, Van Winkle DM (1999) Naloxone blockade of myocardial ischemic preconditioning does not require central nervous system participation. Basic Res Cardiol 94:136–143
Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P, Branham E, Apple FS, Murakami M, Morris DL (2001) Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study. Clin Chem 47:464–470
Dickson EW, Lorbar M, Porcaro WA, Fenton RA, Reinhardt CP, Gysembergh A, Przyklenk K (1999) Rabbit heart can be “preconditioned” via transfer of coronary ef.uent. Am J Physiol 277:H2451–H2457
Doherty NS, Littman BH, Reilly K, Swindell AC, Buss JM, Anderson NL (1998) Analysis of changes in acute-phase plasma proteins in an acute in.ammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis. Electrophoresis 19:355–363
Downey JM, Cohen MV (1996) Preconditioning: markers vs. epiphenomena. Basic Res Cardiol 91:35–37
Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193–200
Gross GJ (1995) ATP-sensitive potassium channels and myocardial preconditioning. Basic Res Cardiol 90:85–88
Heusch G, Schulz R (2002) Remote preconditioning. J Mol Cell Cardiol 34:1279–1281
Jungblut PR, Seifert R (1990) Analysis by high-resolution two-dimensional electrophoresis of differentiation-dependent alterations in cytosolic protein pattern of HL-60 leukemic cells. J Biochem Biophys Methods 21:47–58
Kloner RA, Jennings RB (2001) Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. Circulation 104:2981–2989
Kloner RA, Jennings RB (2001) Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation 104:3158–167
Klose J, Kobalz U (1995) Two-dimensional electrophoresis of proteins: an updated protocol and implications for a functional analysis of the genome. Electrophoresis 16:1034–1059
Konstantinov IE, Li J, Cheung MM, Shimizu M, Stokoe J, Kharbanda RK, Redington AN (2005) Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism. Transplantation 79:1691–1695
Kristiansen SB, Henning O, Kharbanda RK, Nielsen Kudsk JE, Schmidt MR, Redington AN, Nielsen TT, Botker HE (2005) Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol 288: H1252–H1256
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Liauw SK, Rubin BB, Lindsay TF, Romaschin AD, Walker PM (1996) Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage. Am J Physiol 270:H1407–H413
Manthei SA, Van Wylen DG (1997) Purine metabolite accumulation during myocardial ischemia: adenosine pretreatment versus brief ischemia. Basic Res Cardiol 92:368–377
McClanahan T, Nao B, Wolke L, Martin B, Mertz T, Gallagher K (1993) Brief renal occlusion and reperfusion reduces myocardial infarct size in rabbits. FASEB J 7:A118 (Abstract)
Miura T (1996) Adenosine and bradykinin: are they independent triggers of preconditioning? Basic Res Cardiol 91:20–22
Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136
Nakano A, Heusch G, Cohen MV, Downey JM (2002) Preconditioning one myocardial region does not neccessarily precondition the whole rabbit heart. Basic Res Cardiol 97:35–39
Pell TJ, Baxter GF, Yellon DM, Drew GM (1998) Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol 275:H1542–H1547
Piper HM, Ladilov YV (1997) Ischemic preconditioning on the cellular level. Basic Res Cardiol 92 Suppl 2:32–33
Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P (1993) Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87:893–899
Przyklenk K, Darling CE, Dickson EW, Whittaker P (2003) Cardioprotection ‘outside the box’ – the evolving paradigm of remote preconditioning. Basic Res Cardiol 98:149–157
Przyklenk K, Kloner RA (1996) Role of protein kinase C in ischemic preconditioning: in search of the “pure and simple truth”. Basic Res Cardiol 91:41–43
Rohmann S, Weygandt H, Schelling P, Kie Soei L, Verdouw PD, Lues I (1994) Involvement of ATP-sensitive potassium channels in preconditioning protection. Basic Res Cardiol 89:563–576
Steenbergen C (2002) The role of p38 mitogen-activated protein kinase in myocardial ischemia/reperfusion injury; relationship to ischemic preconditioning. Basic Res Cardiol 97:276–285
Takaoka A, Nakae I, Mitsunami K, Yabe T, Morikawa S, Inubushi T, Kinoshita M (1999) Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of “remote preconditioning”. J Am Coll Cardiol 33:556–564
Verdouw PD, van den Doel MA, de Zeeuw S, Duncker DJ (1997) On the relevance of ischemic preconditioning in humans. Basic Res Cardiol 92 Suppl 2:51–53
Weinbrenner C, Nelles M, Herzog N, Sarvary L, Strasser RH (2002) Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non-neuronal but PKC-dependent pathway. Cardiovasc Res 55:590–601
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lang, S.C., Elsässer, A., Scheler, C. et al. Myocardial preconditioning and remote renal preconditioning. Basic Res Cardiol 101, 149–158 (2006). https://doi.org/10.1007/s00395-005-0565-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00395-005-0565-0