Skip to main content
Log in

Ischemic preconditioning in rat heart: No correlation between glycogen content and return of function

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

We tested the hypothesis that glycogen levels at the beginning of ischemia affect lactate production during ischemia and postischemic contractile function.

Isolated working rat hearts were perfused at physiological workload with bicarbonate buffer containing glucose (10 mmol/L). Hearts were subjected to four different preconditioning protocols, and cardiac function was assessed on reperfusion. Ischemic preconditioning was induced by either one cycle of 5 min ischemia followed by 5, 10, or 20 min of reperfusion (PC5/5, PC5/10, PC5/20), or three cycles of 5 min ischemia followed by 5 min of reperfusion (PC3 × 5/5). All hearts were subjected to 15 min total, global ischemia, followed by 30 min of reperfusion. We measured lactate release, timed the return of aortic flow, compared postischemic to preischemic power, and determined tissue metabolites at selected time points.

Compared with preischemic function, cardiac power during reperfusion improved in groups PC5/10 and PC5/20, but was not different from control in groups PC5/5 and PC3 × 5/5. There was no correlation between preischemic glycogen levels and recovery of function during reperfusion. There was also no correlation between glycogen breakdown (or resynthesis) and recovery of function. Lactate accumulation during ischemia was lowest in group PC5/20 and highest in the group with three cycles of preconditioning (PC3 × 5/5). Lactate release during reperfusion was significantly higher in the groups with low recovery of power than in the groups with high recovery of power.

In glucose-perfused rat heart recovery of function is independent from both pre- and postischemic myocardial glycogen content over a wide range of glycogen levels. The ability to utilize lactate during reperfusion is an indicator for postischemic return of contractile function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Murry C, Jennings R, Reimer K: Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium. Circulation 74: 1124–1136, 1986

    Google Scholar 

  2. Reimer K, Vander Heide R, Jennings R: Ischemic preconditioning slows ischemic metabolism and limits myocardial infarct size. Ann NY Acad Sci 723: 99–115, 1994

    Google Scholar 

  3. Asimakis G, Inners-McBride K, Medellin G, Conti V: Ischemic preconditioning attenuates acidosis and postischemic dysfunction in isolated rat hearts. Am J Physiol 263: H887–H894, 1992

    Google Scholar 

  4. Wolfe C, Sievers R, Visseren F, Donnelly T: Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment. Circulation 87: 881–892, 1993

    Google Scholar 

  5. Neely J, Grotyohann L: Role of glycolytic products in damage to myocardium: Dissociation of adenosine triphosphate levels and recovery of function of reperfused canine myocardium. Circ Res 55: 816–824, 1984

    Google Scholar 

  6. McElroy D, Walker W, Taegtmeyer H: Glycogen loading improves left ventricular function of the rabbit heart after hypothermic ischemic arrest. J Appl Cardiol 4: 455–465, 1989

    Google Scholar 

  7. Schneider C, Nguyêñ V, Taegtmeyer H: Feeding and fasting determine postischemic glucose utilization in isolated working rat hearts. Am J Physiol 260: H542–H548, 1991

    Google Scholar 

  8. Schneider C, Taegtmeyer H: Fasting in vivo delays myocardial cell damage after brief periods of ischemia in the isolated working rat heart. Circ Res 68: 1045–1050, 1991

    Google Scholar 

  9. Doenst T, Guthrie P, Chemnitius J-M, Zech R, Taegtmeyer H: Fasting, lactate, and insulin improve ischemia tolerance in rat heart: A comparison with ischemic preconditioning. Am J Physiol 270: H1607–H1615, 1996

    Google Scholar 

  10. Schaefer S, Carr L, Prussel E, Ramasamy R: Effects of glycogen depletion on ischemic injury in isolated rat hearts: Insights into preconditioning. Am J Physiol 268: H935–H944, 1995

    Google Scholar 

  11. Goodwin GW, Taegtmeyer H: Metabolic recovery of the isolated working rat heart after brief global ischemia. Am J Physiol 267: H462–H470, 1994

    Google Scholar 

  12. Lagerstrom C, Walker W, Taegtmeyer H: Failure of glycogen depletion to improve left ventricular function of the rabbit heart after hypothermic ischemic arrest. Circ Res 63: 81–86, 1988

    Google Scholar 

  13. Taegtmeyer H, Hems R, Krebs HA: Utilization of energy providing substrates in the isolated working rat heart. Biochem J 186: 701–711, 1980

    Google Scholar 

  14. Wollenberger A, Ristau O, Schoffa G: Eine einfache Technik der extrem schnellen Abkühlung größerer Gewebsstücke. Pflügers Arch ges Physiol Menschen Tiere 270: 399–412, 1960

    Google Scholar 

  15. Bergmeyer H: Methods of Enzymatic Analysis. 2 edn. Vol. 3. Verlag-Chemie International, Deerfield Beach, 1974, 2000

    Google Scholar 

  16. Walaas O, Walaas E: Effect of epinephrine on rat diaphragm. J Biol Chem 187: 769–776, 1950

    Google Scholar 

  17. Volovsek A, Subramanian R, Reboussin D: Effects of duration of ischemia during preconditioning on mechanical function, enzyme release and energy production in the isolated working rat heart. J Mol Cell Cardiol 24: 1011–1019, 1992

    Google Scholar 

  18. Cave A, Horrowitz G, Apstein C: Can ischemic preconditioning protect against hypoxia induced damage? Studies of contractile function in isolated perfused rat hearts. J Mol Cell Cardiol 26: 1471–1486, 1994

    Google Scholar 

  19. Fralix TA, Steenbergen C, London RE, Murphy E: Metabolic substrates can alter postischemic recovery in preconditioned ischemic heart. Am J Physiol 263: C17–C23, 1992

    Google Scholar 

  20. Jeremy R, Ambrosio G, Pike M, Jacobus W, Becker L: The functional recovery of post-ischemic myocardium requires glycolysis during early reperfusion. J Moll Cell Cardiol 25: 261–276, 1993

    Google Scholar 

  21. Braunwald E, Kloner R: The stunned myocardium: Prolonged, postischemic ventricular dysfunction. Circulation 66: 1146, 1982

    Google Scholar 

  22. Bolli R: Mechanism of myocardial ‘stunning’. Circulation 82: 723–738, 1990

    Google Scholar 

  23. Lawson C, Downey J: Preconditioning: State of the art myocardial protection. Cardiovasc Res 27: 542–550, 1993

    Google Scholar 

  24. Yang X, Arnoult S, Tsuchida A, Cope D, Thornton J, Daly J, Cohen M, Downey J: The protection of ischemic preconditioning can be reinstated in the rabbit heart after the initial protection has waned. Cardiovasc Res 27: 556–558, 1993

    Google Scholar 

  25. Liu Y, Downey J: Ischemic preconditioning protects against infarction in rat heart. Am J Physiol 263: H1107–H1112, 1992

    Google Scholar 

  26. Minhaz U, Koide S, Shohtsu A, Fujishima M, Nakazawa H: Perfusion delay causes unintentional ischemic preconditioning in isolated heart preparation. Basic Res Cardiol 90: 418–423, 1995

    Google Scholar 

  27. Garlick P, Radda G, Seeley P: Studies of acidosis in the ischemic heart by phosphorous NMR. Biochem J 184: 547–554, 1979

    Google Scholar 

  28. Allard M, Emanuel P, Russell J, Bishop S, Digerness S, PG A: Preischemic glycogen reduction or glycolytic inhibition improves postischemic recovery of hypertrophied rat heart. Am J Physiol 267: H66–H74, 1994

    Google Scholar 

  29. Cross H, Opie L, Radda G, Clarke K: Is a high glycogen beneficial or detrimental to the ischemic rat heart? A controversy resolved. Circ Res 78: 482–491, 1996

    Google Scholar 

  30. Asimakis G: Myocardial glycogen depletion cannot explain the cardioprotective effects of ischemic preconditioning in the rat heart. J Mol Cell Cardiol 28: 563–570, 1996

    Google Scholar 

  31. Goodwin G, Arteaga J, Taegtmeyer H: Glycogen turnover in the isolated working rat heart. J Biol Chem 270: 9234–9240, 1995

    Google Scholar 

  32. Clarke K, O'Connor AJ, Willis RJ: Temporal relation between energy metabolism and myocardial function during ischemia and reperfusion. Am J Physiol 253: H412–H421, 1987

    Google Scholar 

  33. Gevers W: Generation of protons by metabolic processes in heart cells. J Mol Cell Cardiol 9: 867, 1977

    Google Scholar 

  34. Lewandowski ED, White LT: Pyruvate dehydrogenase influences postischemic heart function. Circulation 91: 2071–2079, 1995

    Google Scholar 

  35. Russell RR, Taegtmeyer H: Pyruvate carboxylation prevents the decline in contractile function of rat hearts oxidizing acetoacetate. Am J Physiol 261: H756–H762, 1991

    Google Scholar 

  36. Gross G, Auchampach J: Role of ATP dependent potassium channels in myocardial ischemia. Cardiovasc Res 26: 1011–1026, 1992

    Google Scholar 

  37. Ytrehus K, Liu Y, Downey J: Preconditioning protects ischemic rabbit heart by protein kinase C activation. Am J Physiol 266: H1145–H1152, 1994

    Google Scholar 

  38. Morgan H, Henderson M, Regen D, Park C: Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated perfused heart of normal rats. J Biol Chem 236: 253–261, 1961

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doenst, T., Guthrie, P.H. & Taegtmeyer, H. Ischemic preconditioning in rat heart: No correlation between glycogen content and return of function. Mol Cell Biochem 180, 153–161 (1998). https://doi.org/10.1023/A:1006863728395

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006863728395

Navigation