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a Institute of Experimental Medical Research, Faculty Division, Ullevål University Hospital, University of Oslo, Oslo, Norway
b Department of Cardiothoracic Surgery, Ullevål University Hospital, Oslo, Norway
c Department of Surgery, Ullevål University Hospital, Oslo, Norway
Received 24 November 2007; received in revised form 11 March 2008; accepted 13 March 2008.
* Corresponding author. Address: Institute of Experimental Medical Research, Ullevål University Hospital, N-0407 Oslo, Norway. Tel.: +47 97 69 07 30; fax: +47 23 01 67 99. (Email: k.o.stenslokken{at}medisin.uio.no).
Objective: Hydrogen sulphide (H2S) protects the heart against ischaemia–reperfusion injury caused by low flow or local ischaemia. We hypothesised that: (1) H2S protects against global ischaemia–reperfusion injury of the heart, (2) H2S plays a mechanistic role in ischaemic preconditioning, and (3) H2S acts by phosphorylation of protein kinases. Methods: Isolated, perfused rat hearts were used in two series. Series 1: group 1.1 (n = 10), 40 min of ischaemia and 120 min of reperfusion, group 1.2 (n = 7), like 1.1 except that 40 µM NaHS was added to the perfusate during stabilisation and throughout the experiment. Group 1.3 (n = 10), like 1.1, but endogenously produced H2S was blocked by D,L-propargylglycine. Series 2: group 2.1 (n = 10) control, 30 min of ischaemia followed by 120 min of reperfusion. Group 2.2 (n = 10) ischaemic preconditioning before sustained ischaemia and 120 min of reperfusion. Group 2.3 (n = 10) like 2.2 except of D,L-propargylglycine treatment like in group 1.3. Mitogen activated protein kinases including extracellular signal-regulated kinases (ERK 1/2), the stress-activated/c-Jun NH2 terminal kinases (JNK), P38, as well as protein kinase B/AKT (AKT), adenosine monophosphate dependent protein kinase (AMPK) and the inducible heat shock protein 72 were measured by Western blotting. Adenine nucleotides (ATP, ADP, and AMP) were measured by high-pressure liquid chromatography and energy charge was calculated. Results: Infarct size was increased by D,L-propargylglycine (40 ± 6 vs 27 ± 10% in controls, p = 0.03, Bonferroni post hoc test). There was a non-significant decrease in infarct size in the NaHS group (to 20 ± 13%). Western blot analysis indicated an upregulation of heat shock protein 72 in the NaHS treated group and a reduced phosphorylation of AKT in the D,L-propargylglycine group. D,L-Propargylglycine had no effect on ischaemic preconditioning or on phosphorylation of protein kinases (ERK, AKT, P38, JNK and AMPK) in preconditioned hearts. No difference in energy charge was found between groups, although ADP was increased in the NaHS-treated group. Conclusion: Endogenous H2S production protects against global ischaemia, and H2S may be a part of the endogenous cell defence. However, endogenous H2S did not appear to be important in ischaemic preconditioning, and protein kinases were not important for the effect of H2S. Exogenous H2S may provide myocardial protection, possibly acting by expression of heat shock protein 72.
Key Words: Hydrogen sulphide • Ischaemia • Reperfusion • Heat shock protein 72 • Mitogen activated protein kinases • Adenine nucleotides • Energy charge
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  Q. C. Yong, S. W. Lee, C. S. Foo, K. L. Neo, X. Chen, and J.-S. Bian Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1330 - H1340. [Abstract] [Full Text] [PDF]
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