© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Extracellular adenosine levels and cellular energy metabolism in ischemically preconditioned rat heart
Rotary Centre for Cardiovascular Research, School of Health Sciences, Griffith University Gold Coast Campus, QLD 4217, Australia
* Corresponding author. Tel.: +61 7 5594 8519; Fax: +61 7 5594 8908; E-mail: g.harrison@gu.edu.au
Objective: Microdialysis and 31P-NMR spectroscopy were used to test opposing hypotheses that ischemic preconditioning inhibits adenine nucleotide degradation and purine efflux, or that preconditioning activates cardiovascular adenosine formation to provide enhanced cardioprotection. Methods: 31P-NMR spectra and matching interstitial fluid (ISF) or venous effluent samples were obtained from Langendorff perfused rat hearts. Control hearts (n=9) underwent 30 min of global normothermic ischemia and 30 min reperfusion. Preconditioned hearts (n=6) were subjected to a 5 min ischemic episode and 10 min reflow prior to 30 min ischemia and 30 min reperfusion. Effects of repetitive ischemia–reperfusion (3x5 min ischemic episodes) on adenosine levels and energy metabolism were also assessed (n=8). Results: Preconditioning improved post-ischemic recovery of heart rate x left ventricular developed pressure (71±5 vs 43±8%, P<0.05) and end-diastolic pressure (14±3 vs 29±4 mmHg, P<0.05) compared with control hearts, respectively. Preconditioning did not alter intracellular ATP, phosphocreatine (PCr), inorganic phosphate (Pi), H+ or free Mg2+ during global ischemia, but improved recoveries of PCr, Pi, and 
GATP on reperfusion. ISF adenosine increased more than 20-fold during 30 min ischemia. The 5 min preconditioning episode increased ISF adenosine 3-fold, and reduced ISF adenosine and inosine during subsequent prolonged ischemia by up to 75%. Venous purine levels during reperfusion were also reduced by preconditioning. Accumulation of adenosine in ISF and venous effluent during repetitive ischemia was progressively reduced despite comparable changes in substrate for adenosine formation via 5'-nucleotidase (5'-AMP), and in allosteric modulators of this enzyme (Mg2+, H+, Pi, ADP, ATP). Conclusions: (i) Ischemic preconditioning reduces interstitial and vascular adenosine levels during ischemia–reperfusion, (ii) reduced ISF adenosine during ischemia is not due to reduced ischemic depletion of adenine nucleotides in preconditioned rat hearts, (iii) preconditioning may inhibit adenosine formation via 5'-nucleotidase in ischemic rat hearts, and (iv) improved functional recovery with preconditioning is unrelated to metabolic/bioenergetic changes during the ischemic insult, but may be related to improved post-ischemic recovery of [Pi] and GATP in this model.
KEYWORDS Adenosine; Preconditioning; Energy metabolism; Microdialysis; 31P-NMR; Rat
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Wee, J. N. Peart, and J. P. Headrick P2 Purinoceptor-Mediated Cardioprotection in Ischemic-Reperfused Mouse Heart J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 861 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Pierre, C. Yang, Z. Yuan, J. Seminerio, C. Mouas, K. D. Garlid, P. Dos-Santos, and Z. Xie Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts Cardiovasc Res, February 1, 2007; 73(3): 488 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Reichelt, L. Willems, J. N. Peart, K. J. Ashton, G. P. Matherne, M. R. Blackburn, and J. P. Headrick Heart/Cardiac Muscle: Modulation of ischaemic contracture in mouse hearts: a 'supraphysiological' response to adenosine Exp Physiol, January 1, 2007; 92(1): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. V. Solenkova, V. Solodushko, M. V. Cohen, and J. M. Downey Endogenous adenosine protects preconditioned heart during early minutes of reperfusion by activating Akt Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H441 - H449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fenning, G. Harrison, R. Rose'meyer, A. Hoey, and L. Brown L-Arginine attenuates cardiovascular impairment in DOCA-salt hypertensive rats Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1408 - H1416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, K. Nakamura, Y. Ito, T. Uzuka, M. Morikawa, S. Hirai, K. Tomihara, T. Tanaka, Y. Masuta, K. Ishii, et al. Bcl-xL Gene Transfer Inhibits Bax Translocation and Prolongs Cardiac Cold Preservation Time in Rats Circulation, July 5, 2005; 112(1): 76 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kin, A. J. Zatta, M. T. Lofye, B. S. Amerson, M. E. Halkos, F. Kerendi, Z.-Q. Zhao, R. A. Guyton, J. P. Headrick, and J. Vinten-Johansen Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine Cardiovasc Res, July 1, 2005; 67(1): 124 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Peart and G. J. Gross Morphine-Tolerant Mice Exhibit a Profound and Persistent Cardioprotective Phenotype Circulation, March 16, 2004; 109(10): 1219 - 1222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Headrick, B. Hack, and K. J. Ashton Acute adenosinergic cardioprotection in ischemic-reperfused hearts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mubagwa and W. Flameng Adenosine, adenosine receptors and myocardial protection: An updated overview Cardiovasc Res, October 1, 2001; 52(1): 25 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Peart and J. P. Headrick Intrinsic A1 adenosine receptor activation during ischemia or reperfusion improves recovery in mouse hearts Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2166 - H2175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A Gustafson, C. J Zuurbier, J. E Bassett, J. P. F Barends, J. H.G.M van Beek, J. B Bassingthwaighte, and K. Kroll Increased hypoxic stress decreases AMP hydrolysis in rabbit heart Cardiovasc Res, November 1, 1999; 44(2): 333 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ninomiya, H. Otani, K. Lu, T. Uchiyama, M. Kido, and H. Imamura Complementary role of extracellular ATP and adenosine in ischemic preconditioning in the rat heart Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1810 - H1820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ninomiya, H. Otani, K. Lu, T. Uchiyama, M. Kido, and H. Imamura Enhanced IPC by activation of pertussis toxin-sensitive and -insensitive G protein-coupled purinoceptors Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1933 - H1943. [Abstract] [Full Text] [PDF]
|
|