scholarly journals 017 Concentration-dependent protection by no donors against ischaemia-reperfusion injury in perfused rat hearts

Heart ◽  
2010 ◽  
Vol 96 (4) ◽  
pp. e5-e6
Author(s):  
W. H. Y. Cheng ◽  
A. P. Halestrap ◽  
E. J. Griffiths
Keyword(s):  
Reperfusion Injury ◽  
Ischaemia Reperfusion Injury ◽  
No Donors ◽  
Ischaemia Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts

scholarly journals Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury and preconditioning: implications for pathology and cardioprotection

2006 ◽  
Vol 395 (3) ◽  
pp. 611-618 ◽  
Author(s):  
Sergiy M. Nadtochiy ◽  
Andrew J. Tompkins ◽  
Paul S. Brookes
Keyword(s):  
Reperfusion Injury ◽  
Kinase Inhibitor ◽  
Adenine Nucleotide ◽  
Treatment Strategies ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts

The mechanisms of mitochondrial proton (H+) leak under various pathophysiological conditions are poorly understood. In the present study it was hypothesized that different mechanisms underlie H+ leak in cardiac IR (ischaemia/reperfusion) injury and IPC (ischaemic preconditioning). Potential H+ leak mechanisms examined were UCPs (uncoupling proteins), allosteric activation of the ANT (adenine nucleotide translocase) by AMP, or the PT (permeability transition) pore. Mitochondria isolated from perfused rat hearts that were subjected to IPC exhibited a greater H+ leak than did controls (202±27%, P<0.005), and this increased leakage was completely abolished by the UCP inhibitor, GDP, or the ANT inhibitor, CAT (carboxyattractyloside). Mitochondria from hearts subjected to IR injury exhibited a much greater amount of H+ leak than did controls (411±28%, P<0.001). The increased leakage after IR was weakly inhibited by GDP, but was inhibited, >50%, by carboxyattractyloside. In addition, it was inhibited by cardioprotective treatment strategies including pre-IR perfusion with the PT pore inhibitors cyclosporin A or sanglifehrin A, the adenylate kinase inhibitor, AP5A (diadenosine pentaphosphate), or IPC. Together these data suggest that the small increase in H+ leak in IPC is mediated by UCPs, while the large increase in H+ leak in IR is mediated by the ANT. Furthermore, under all conditions studied, in situ myocardial O2 efficiency was correlated with isolated mitochondrial H+ leak (r2=0.71). In conclusion, these data suggest that the modulation of H+ leak may have important implications for the outcome of IR injury.

Upregulation of CaMKIIδ during ischaemia–reperfusion is associated with reperfusion-induced arrhythmias and mechanical dysfunction of the rat heart: involvement of sarcolemmal Ca2+-cycling proteins

2012 ◽  
Vol 90 (8) ◽  
pp. 1127-1134 ◽  
Author(s):  
Adriana Adameova ◽  
Slavka Carnicka ◽  
Tomas Rajtik ◽  
Adrian Szobi ◽  
Martina Nemcekova ◽  
...  
Keyword(s):  
Sodium Calcium Exchanger ◽  
Ischaemia Reperfusion Injury ◽  
Global Ischaemia ◽  
Ischaemia Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Dependent Protein ◽  
Chronotropic Effects ◽  
Cardiac Stunning ◽  
Contractile Recovery

Although Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) has been implicated in development of different phenotypes of myocardial ischaemia–reperfusion injury, its involvement in arrhythmogenesis and cardiac stunning is not sufficiently elucidated. Moreover, the mechanisms by which CaMKIIδ mediates disturbances in excitation–contraction coupling, are not exactly known. To investigate this, KN-93 (0.5 µmol/L), a CaMKII inhibitor, was administered before induction of global ischaemia and reperfusion in isolated Langendorff-perfused rat hearts. Expression of CaMKIIδ and the sarcollemal Ca2+-cycling proteins, known to be activated during reperfusion, was analyzed using immunoblotting. KN-93 reduced reperfusion-induced ectopic activity and the incidence of ventricular fibrillation. Likewise, the severity of arrhythmias was lower in KN-treated hearts. During the pre-ischaemia phase, neither inotropic nor chronotropic effects were elicited by KN-93, whereas post-ischaemic contractile recovery was significantly improved. Ischaemia–reperfusion increased the expression of CaMKIIδ and sodium–calcium exchanger (NCX1) proteins without any influence on the protein content of alpha 1c, a pore-forming subunit of L-type calcium channels (LTCCs). On the other hand, inhibition of CaMKII normalized changes in the expression of CaMKIIδ and NCX1. Taken together, CaMKIIδ seems to regulate its own turnover and to be an important component of cascade integrating NCX1, rather than LTCCs that promote ischaemia–reperfusion-induced contractile dysfunction and arrhythmias.

scholarly journals Monophosphoryl lipid A provides biphasic cardioprotection against ischaemia-reperfusion injury in rat hearts

1999 ◽  
Vol 128 (2) ◽  
pp. 412-418 ◽  
Author(s):  
Nobushige Yamashita ◽  
Shiro Hoshida ◽  
Kinya Otsu ◽  
Naoyuki Taniguchi ◽  
Tsunehiko Kuzuya ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Lipid A ◽  
Ischaemia Reperfusion Injury ◽  
Monophosphoryl Lipid A ◽  
Ischaemia Reperfusion ◽  
Monophosphoryl Lipid ◽  
Rat Hearts

Up-regulation of endothelin-converting-enzyme mRNA expression following cardioplegic arrest

2002 ◽  
Vol 103 (s2002) ◽  
pp. 206S-209S ◽  
Author(s):  
Andrew T. GOODWIN ◽  
Mahboob A. KHAN ◽  
Adrian H. CHESTER ◽  
Mohamed AMRANI ◽  
Magdi H. YACOUB
Keyword(s):  
Reperfusion Injury ◽  
Mrna Expression ◽  
Housekeeping Gene ◽  
Converting Enzyme ◽  
Cardioplegic Arrest ◽  
Ischaemia Reperfusion Injury ◽  
Reverse Transcription Pcr ◽  
Ischaemia Reperfusion ◽  
Normothermic Perfusion ◽  
Rat Hearts

Endothelin-1 (ET-1) is believed to play an important role in cardiac ischaemia/reperfusion injury. ET-1 is synthesized from preproET-1 by the action of ET-converting enzyme (ECE). It is unclear to what extent the ET system is activated following prolonged ischaemia. In this study we used a model mimicking the conditions of the donor heart during transplantation. Isolated rat hearts perfused with Krebs–Henseleit buffer were subjected to 30min of normothermic perfusion, then 4h of cardioplegic arrest at 4°C with St Thomas' Hospital solution, followed by reperfusion for 2h. Hearts were freeze-clamped at different time points during the protocol. Using quantitative reverse transcription–PCR, relative levels of ET-1 and ECE mRNA expression were measured and compared with a housekeeping gene (ribosomal protein L32). During reperfusion there was a consistent decrease in coronary flow to approx. 85–90% of pre-ischaemic flow. There was no significant alteration in preproET-1 mRNA expression during 2h of reperfusion. However, ECE mRNA expression was increased by 77.5% at 1h and by 74.6% at 2h following ischaemia compared with pre-ischaemic values (P<0.05). Thus we conclude that ECE mRNA expression is increased following prolonged hypothermic cardioplegic arrest. Elevations in the expression of this enzyme may help to explain the role of the ET system in the pathogenesis of ischaemia/reperfusion injury following cardiac surgery and transplantation.

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