Skip to main content
Log in

Epinephrine-stimulated contractile and metabolic reserve in postischemic rat myocardium

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

Recovery of contractilc function and of fatty acid oxidation may be delayed in viable postischemic myocardium. To determine whether a metabolic reserve is preserved after reperfusion of reversibly injured myocardium, we studied the effect of epinephrine on myocardial fatty acid oxidation in isolated rat hearts perfused retrogradely with crythrocyte enriched buffer containing albumin 0.4 mM, palmitate 0.4 mM, and glucose 11 mM. Hearts were subjected to 60 min of low-flow ischemia (5% of control flow) followed by 60 min of reperfusion. Five minutes following the onset of reperfusion, developed left ventricular pressure (DLVP) and oxidation of palmitate were reduced to 53% (p<0.01) and 46% (p<0.01), respectively, of values measured in nonischemic control hearts. Subsequently, DLVP and oxidation of palmitate gradually recovered to 78% (NS) and 91% (NS) by 60 min of reperfusion. Epinephrine 5·10−4M elicited an immediate stimulation of both contractile function and palmitate oxidation. Early after reperfusion stimulated DLVP and palmitate oxidation were still lower compared to values measured in control hearts exposed to the same concentration of epinephrine. Later than 15 min after the onset of reperfusion the response of DLVP and of palmitate oxidation to epinephrine no longer differed between control and reperfused hearts.

These results indicate that viable postischemic myocardium exhibits a remarkable oxidative metabolic reserve. The observation provides further evidence for the view that impairment of myocardial energy production is not responsible for contractilc dysfunction early after reperfusion.

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. Ambrosio G, Jacobus WE, Bergman A, Weisman HF, Becker LC (1987) Preserved high energy phosphate metabolic reserve in globally “stunned” hearts despite reduction of basal ATP content and contractility. J Mol Cell Cardiol 19:953–964

    PubMed  Google Scholar 

  2. Arnold JM, Braunwald E, Sandor T, Kloner RA (1985) Inotropic stimulation of reperfused myocardium with dopamine: Effects on infarct sizc and myocardial function. J Am Coll Cardiol 6:1026–1043

    PubMed  Google Scholar 

  3. Becker LC, Levine JH, DiPaula AF, Guarnieri T, Aversano T (1986) Reversal of dysfunction in postischemic stunned myocardium by epinephrine and postextrasystolic potentiation. J Am Coll Cardiol 7:580–589

    PubMed  Google Scholar 

  4. Bergmann SR, Carlson E, Dannen E, Sobel BE (1980) An improved assay with 4-(2)-thiazolylazoresochinol for non-esterified fatty acids in biological fluids. Chim Acta 104:53–63

    Google Scholar 

  5. Braunwald E, Kloner RA (1983) The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 66:1146–1149

    Google Scholar 

  6. Bolli R, Zhu WL, Myers ML, Harteley CJ, Roberts R (1985) Beta-adrenergic stimulation reverses postischemic myocardial dysfunction without producing subsequent functional deterioration. Am J Cardiol 56:964–968

    PubMed  Google Scholar 

  7. Chatelain P, Papageorgiou I, Lüthy P, Melchor JP, Rutishauser W, Lerch R (1987) Free fatty acid metabolism in “stunned” myocardium. Basic Res Cardiol (Supplement):169–176

    Google Scholar 

  8. Ciuffo AA, Ouyang P, Becker LC, Levine L, Weisfeldt ML (1986) Reduction of sympathetic inotropic response after ischemia in dogs. Contributor to stunned myocardium. J Clin Invest 75:1504–1509

    Google Scholar 

  9. Edoute Y, van der Mcrwe E, Sanan D, Kotze JCN, Steinman C, Lochner A (1983) Normothermic ischemic cardiac arrest of isolated working rat heart. Effect of time and reperfusion on myocardial ultrastructure, mitochondrial oxidative function, and myocardial recovery. Circ Res 53:663–678

    PubMed  Google Scholar 

  10. Ellis SG, Wynne J, Braunwald E, Henschje CT, Sandor T, Kloner RA (1984) Response of reperfused-salvaged, stunned myocardium to inotropic stimulation. Am Heart J 107:13–19

    PubMed  Google Scholar 

  11. Görge G, Papageorgiou I, Lerch R (1988) Fatty acid metabolism in post-ischemic myocardium: Effect of different degrees of ischemic damage (abstract). J Mol Cell Cardiol 20 (Supplement V):67

    Google Scholar 

  12. Ito BI, Tate H, Kobayashi M, Schaper W (1987) Reversibly injured, postischemic canine myocardium retains normal contractile reserve. Circ Res 61:834–846

    PubMed  Google Scholar 

  13. Kreisberg RA (1966) Effect of epinephrine on myocardial triglyceride and free fatty acid utilization. Am J Physiol 210:385–389

    PubMed  Google Scholar 

  14. Lamprecht W, Stein P, Heinz F, Weisser H (1974) Creatinephosphate determination with creatine kinase, hexokinase, and glucose-6-phosphate dehydrogenase. In: Bergmeyer HU (ed) Methods of Enzymatic Analysis. Vol 4, Academic Press, New York, pp 1777–1781

    Google Scholar 

  15. Lamprecht W, Trautschold I (1974) Adenosine 5-triphosphate determination with hexokinase and glucose-6-phosphate dehydrogenase. In: Bergmeyer HU (ed) Methods of Enzymatic Analysis. Vol 4, Academic Press, New York, pp 2101–2110

    Google Scholar 

  16. Laster SB, Becker LC, Ambrosio G, Jacobus WE (1986) Reduced aerobic metabolic efficiency in stunned myocardium (abstract). Circulation 74:II-354

    Google Scholar 

  17. Laxson DD, Homans DC, Dai XC, Sublett E, Bache RJ (1989) Oxygen consumption and coronary reactivity in postischemic myocardium. Circ Res 63:1–15

    Google Scholar 

  18. Lerch R, Görge G, Papageorgiou I, Benzi R, Rutishauser W (1989) Le métabolisme oxidatif dans le myocard reperfusé (abstract). Schweiz Med Wschr (Supplement 27):17

    Google Scholar 

  19. Liedtke AJ (1981) Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis 23:321–336

    PubMed  Google Scholar 

  20. Liedtke AJ, DeMaison L, Eggleston AM, Cohen LM, Nellis SH (1988) Changes in substrate metabolism and effect of excess fatty acids in reperfused myocardium. Circ Res 62:535–542

    PubMed  Google Scholar 

  21. Lopaschuk GD, Spafford MA, Davies NJ, Wall SR (1990) Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ Res 66:546–553

    PubMed  Google Scholar 

  22. Mercier JC, Lando U, Kanmatsuse K, Ninimiya K, Meerbaum S, Fishbein MC, Swan HJC, Ganz W (1982) Divergent effects of inotropic stimulation on the ischemic and severely depressed reperfused myocardium. Circulation 66:397–400

    PubMed  Google Scholar 

  23. Myears DW, Sobel BE, Bergmann SR (1987) Substrate use in ischemic reperfused canine myocardium: Quantitative considerations. Am J Physiol 253:H107-H114

    PubMed  Google Scholar 

  24. Neubauer S, Hamman BL, Perry SB, Bittl JS, Ingwall JS (1988) Velocity of the creatine kinase reaction decreases in postischemic myocardium: A 31P-NMR magnetization transfer study of the isolated ferret heart. Circ Res 63:1–15

    PubMed  Google Scholar 

  25. Reimer RA, Hill ML, Jennings RB (1981) Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs. J Mol Cell Cardiol 13:229–239

    PubMed  Google Scholar 

  26. Schwaiger M, Schelbert HR, Keen R, Vinten-Johansen J, Hansen H, Selin C, Barrio J, Huang SC, Phelps ME (1985) Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium. J Am Coll Cardiol 6:311–320

    PubMed  Google Scholar 

  27. Schwaiger M, Schelbert HR, Ellison D, Hansen H, Yeatman L, Vinten-Johansen J, Selin C, Barrio J, Phelps ME (1985) Sustained regional abnormalitics in cardiac metabolism after transient ischemia in the chronic dog model. J Am Coll Cardiol 6:336–347

    PubMed  Google Scholar 

  28. Schwaiger M, Neese R, Araujo L, Wyns W, Wisneski JA, Sochor H, Swank S, Kulber D, Selin C, Phelps M, Schelbert HR, Fishbein MC, Gertz EW (1989) Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium. J Am Coll Cardiol 13:745–754

    PubMed  Google Scholar 

  29. Simoons ML, Serruys PW, van den Brand M, Res J, Verheugt FWA, Krauss XH, Remme WJ, Bär F, de Zwaan C, van der Laarse A, Vermeer F, Lubsen J (1986) Early thrombolysis in acute myocardial infarction: Limitation of infarct size and improved survival. J Am Coll Cardiol 7:717–728

    PubMed  Google Scholar 

  30. Stahl LD, Weiss HR, Becker LC (1988) Myocardial oxygen consumption, oxygen supply/demand heterogeneity, and microvascular patency in regionally stunned myocardium. Circulation 77:865–872

    PubMed  Google Scholar 

  31. Trach V, Buschmanns-Denkel E, Schaper W (1986) Relation between lipolysis and glycolysis during ischemia in the isolated rat heart. Basic Res Cardiol 81:454–464

    PubMed  Google Scholar 

  32. Vercesi A, Reynafarje B, Lehninger A (1978) Stoichiometry of H+ ejection and Ca++ uptake coupled to electron transport in rat heart mitochondria. J Biol Chem 253:6379–6385

    PubMed  Google Scholar 

  33. Wallenstein S, Zucker CL, Fleiss JL (1980) Some statistical methods useful in Circulation Research. Circ Res 47:1–9

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the Swiss National Science Foundation grant # 3.917-0.87

Rights and permissions

Reprints and permissions

About this article

Cite this article

Görge, G., Papageorgiou, I. & Lerch, R. Epinephrine-stimulated contractile and metabolic reserve in postischemic rat myocardium. Basic Res Cardiol 85, 595–605 (1990). https://doi.org/10.1007/BF01907894

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01907894

Key words

Navigation