Circulation, Vol 87, 881-892, Copyright © 1993 by American Heart Association
CL Wolfe, RE Sievers, FL Visseren and TJ Donnelly
BACKGROUND. Although previous investigators have demonstrated that
myocardial preconditioning reduces infarct size, the mechanisms of
cardioprotection associated with preconditioning are not completely
understood. METHODS AND RESULTS. To test the hypothesis that
preconditioning (four 5-minute episodes of ischemia each followed by 5
minutes of reperfusion) reduces infarct size by depleting cardiac glycogen
stores and attenuating the degree of intracellular acidosis during
subsequent prolonged left coronary artery occlusion, preconditioned and
control rats were subjected to 45 minutes of left coronary artery occlusion
and 120 minutes of reflow immediately after preconditioning (groups 1P and
1C, respectively) or after 30 minutes (groups 2P+30m and 2C), 1 hour
(groups 3P+60m and 3C), or 6 hours (groups 4P+360m and 4C) of nonischemic
recovery after preconditioning but before prolonged ischemia. In each
group, cardiectomy was performed in selected rats immediately before
prolonged ischemia for cardiac glycogen assay. In selected animals, 31P
magnetic resonance spectroscopy was performed to monitor intracellular pH
and measure high- energy phosphate levels during ischemia and reperfusion.
Group 1P rats demonstrated marked glycogen depletion after preconditioning
compared with controls (0.72 +/- 0.39 [n = 9] versus 5.67 +/- 1.73 [n = 12]
mg glucose/g wet wt; p < 0.001 versus group 1C) that was associated with
attenuation of intracellular acidosis during ischemia, as measured by 31P
magnetic resonance spectroscopy (6.8 +/- 0.3 [n = 11] versus 6.2 +/- 0.3 [n
= 9] pH units; p < 0.01), and marked infarct size reduction (0.3 +/-
0.6% [n = 7] versus 38.1 +/- 11.3% [n = 7], infarct size divided by risk
area; p < 0.0001). During ischemia, there were no differences in
myocardial ATP or phosphocreatine levels or in any hemodynamic determinant
of myocardial oxygen demand between groups 1P and 1C. In preconditioned
rats that were allowed to recover before ischemia (groups 2P+30m, 3P+60m,
and 4P+360m), the time course of glycogen repletion paralleled the loss of
protection from ischemic injury. CONCLUSIONS. Glycogen depletion and the
attenuation of intracellular acidosis during ischemia appear to be
important factors in delaying irreversible injury and reducing infarct size
in this animal model of myocardial preconditioning.
ARTICLES
Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment
Cardiovascular Research Institute, University of California, San Francisco 94143-0124.
This article has been cited by other articles:
 |
|
 |
|
  M. Gandhi, B. A. Finegan, and A. S. Clanachan Role of glucose metabolism in the recovery of postischemic LV mechanical function: effects of insulin and other metabolic modulators Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2576 - H2586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and C. Steenbergen Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury Physiol Rev, April 1, 2008; 88(2): 581 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Omar, H. Fraser, and A. S. Clanachan Ischemia-induced activation of AMPK does not increase glucose uptake in glycogen-replete isolated working rat hearts Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1266 - H1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Tracey, J. L. Treadway, W. P. Magee, J. C. Sutt, R. K. McPherson, C. B. Levy, D. E. Wilder, L. J. Yu, Y. Chen, R. M. Shanker, et al. Cardioprotective effects of ingliforib, a novel glycogen phosphorylase inhibitor Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1177 - H1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A J Krijnen, R Nijmeijer, C J L M Meijer, C A Visser, C E Hack, and H W M Niessen Apoptosis in myocardial ischaemia and infarction J. Clin. Pathol., November 1, 2002; 55(11): 801 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schulz, M. V Cohen, M. Behrends, J. M Downey, and G. Heusch Signal transduction of ischemic preconditioning Cardiovasc Res, November 1, 2001; 52(2): 181 - 198. [Full Text] [PDF]
|
|
|
|
 |
|
 A Sola, J Rosello-Catafau, E Gelpi, and G Hotter Fructose-1,6-biphosphate in rat intestinal preconditioning: involvement of nitric oxide Gut, February 1, 2001; 48(2): 168 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Tracey, W. P. Magee, C. A. Ellery, J. T. MacAndrew, A. H. Smith, D. R. Knight, and P. J. Oates Aldose reductase inhibition alone or combined with an adenosine A3 agonist reduces ischemic myocardial injury Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1447 - H1452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Ganote and S. C. Armstrong Adenosine and preconditioning in the rat heart Cardiovasc Res, January 1, 2000; 45(1): 134 - 140. [Full Text] [PDF]
|
|
|
|
|
|
C. A Piot, J.-F. Martini, S. K Bui, and C. L Wolfe Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo Cardiovasc Res, December 1, 1999; 44(3): 536 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tian, W. Miao, M. Spindler, M. M. Javadpour, R. McKinney, J. C. Bowman, P. M. Buttrick, and J. S. Ingwall Long-term expression of protein kinase C in adult mouse hearts improves postischemic recovery PNAS, November 9, 1999; 96(23): 13536 - 13541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takeo and Y. Nasa Role of energy metabolism in the preconditioned heart - a possible contribution of mitochondria Cardiovasc Res, July 1, 1999; 43(1): 32 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fraser, G. D. Lopaschuk, and A. S. Clanachan Assessment of glycogen turnover in aerobic, ischemic, and reperfused working rat hearts Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1533 - H1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. HEUSCH Hibernating Myocardium Physiol Rev, October 1, 1998; 78(4): 1055 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Harrison, R. J. Willis, and J. P. Headrick Extracellular adenosine levels and cellular energy metabolism in ischemically preconditioned rat heart Cardiovasc Res, October 1, 1998; 40(1): 74 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. F. Rehring, J. I. Shapiro, B. S. Cain, D. R. Meldrum, J. C. Cleveland, A. H. Harken, and A. Banerjee Mechanisms of pH preservation during global ischemia in preconditioned rat heart: roles for PKC and NHE Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H805 - H813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Lee, R. E. Sievers, G. J. Gallinghouse, and P. C. Ursell Development of a model of complete heart block in rats J Appl Physiol, August 1, 1998; 85(2): 758 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Arai, S. Minatoguchi, G. Takemura, Y. Uno, T. Kariya, H. Takatsu, T. Fujiwara, M. Higashioka, Y. Yoshikuni, and H. Fujiwara N-Methyl-1-Deoxynojirimycin (MOR-14), an {alpha}-Glucosidase Inhibitor, Markedly Reduced Infarct Size in Rabbit Hearts Circulation, April 7, 1998; 97(13): 1290 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Green, H. N. Murray, P. G. Sleph, F.-L. Wang, A. J. Baird, W. L. Rogers, and G. J. Grover Preconditioning in rat hearts is independent of mitochondrial F1F0 ATPase inhibition Am J Physiol Heart Circ Physiol, January 1, 1998; 274(1): H90 - H97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M Yellon, G. F Baxter, D. Garcia-Dorado, G. Heusch, and M. S Sumeray Ischaemic preconditioning: present position and future directions Cardiovasc Res, January 1, 1998; 37(1): 21 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Shipolini, H. Yokoyama, M. Galinanes, S. J. Edmondson, D. J. Hearse, and M. Avkiran Na+/H+ Exchanger Activity Does Not Contribute to Protection by Ischemic Preconditioning in the Isolated Rat Heart Circulation, November 18, 1997; 96(10): 3617 - 3625. [Abstract] [Full Text]
|
|
|
|
|
|
S. A. Gabel, H. R. Cross, R. E. London, C. Steenbergen, and E. Murphy Decreased intracellular pH is not due to increased H+ extrusion in preconditioned rat hearts Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2257 - H2262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Piot, D. Padmanaban, P. C. Ursell, R. E. Sievers, and C. L. Wolfe Ischemic Preconditioning Decreases Apoptosis in Rat Hearts In Vivo Circulation, September 2, 1997; 96(5): 1598 - 1604. [Abstract] [Full Text]
|
|
|
|
|
|
K.-i. Yabe, Y. Nasa, M. Sato, R. Iijima, and S. Takeo Preconditioning preserves mitochondrial function and glycolytic flux during an early period of reperfusion in perfused rat hearts Cardiovasc Res, March 1, 1997; 33(3): 677 - 685. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Birnbaum, K. Przyklenk, and R. A. Kloner Time Frame of Ischemic Preconditioning: Is It Clinically Relevant? Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 1996; 1(4): 339 - 346. [PDF]
|
|
|
|
|
|
J. J. Hutter, R. Mestril, E. K.W. Tam, R. E. Sievers, W. H. Dillmann, and C. L. Wolfe Overexpression of Heat Shock Protein 72 in Transgenic Mice Decreases Infarct Size In Vivo Circulation, September 15, 1996; 94(6): 1408 - 1411. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. G. Weiss, C. P. de Albuquerque, K. Vandegaer, V.P. Chacko, and G. Gerstenblith Attenuated Glycogenolysis Reduces Glycolytic Catabolite Accumulation During Ischemia in Preconditioned Rat Hearts Circ. Res., September 1, 1996; 79(3): 435 - 446. [Abstract] [Full Text]
|
|
|
|
|
|
H. R. Cross, L. H. Opie, G. K. Radda, and K. Clarke Is a High Glycogen Content Beneficial or Detrimental to the Ischemic Rat Heart? : A Controversy Resolved Circ. Res., March 1, 1996; 78(3): 482 - 491. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Auyeung, R. E. Sievers, D. Weng, V. Barbosa, and C. L. Wolfe Catalase Inhibition With 3-Amino-1,2,4-Triazole Does Not Abolish Infarct Size Reduction in Heat-Shocked Rats Circulation, December 1, 1995; 92(11): 3318 - 3322. [Abstract] [Full Text]
|
|
|
|
|
|
R. Schulz, H. Post, S. Sakka, D. R. Wallbridge, and G. Heusch Intraischemic Preconditioning : Increased Tolerance to Sustained Low-Flow Ischemia by a Brief Episode of No-Flow Ischemia Without Intermittent Reperfusion Circ. Res., June 1, 1995; 76(6): 942 - 950. [Abstract] [Full Text]
|
|
|
|
|
|
E. Murphy, W. Glasgow, T. Fralix, and C. Steenbergen Role of Lipoxygenase Metabolites in Ischemic Preconditioning Circ. Res., March 1, 1995; 76(3): 457 - 467. [Abstract] [Full Text]
|
|
|
|
|
|
M. B. Mitchell, X. Meng, L. Ao, J. M. Brown, A. H. Harken, and A. Banerjee Preconditioning of Isolated Rat Heart Is Mediated by Protein Kinase C Circ. Res., January 1, 1995; 76(1): 73 - 81. [Abstract] [Full Text]
|
|
|
|
|
|
A. K. Jonassen, M. N. Sack, O. D. Mjos, and D. M. Yellon Myocardial Protection by Insulin at Reperfusion Requires Early Administration and Is Mediated via Akt and p70s6 Kinase Cell-Survival Signaling Circ. Res., December 7, 2001; 89(12): 1191 - 1198. [Abstract] [Full Text] [PDF]
|
|