Advertisement

Features of short-term myocardial hibernation

  • Gerd Heusch
  • Rainer Schulz
Part of the Molecular and Cellular Biochemistry book series (DMCB, volume 28)

Abstract

When severe ischemia, such as that resulting from a sudden and complete coronary artery occlusion, is prolonged for more than 20-40 min, myocardial infarction develops, and there is irreversible loss of contractile function. When myocardial ischemia is less severe but nevertheless prolonged, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of ‘perfusion-contraction matching’ exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed’ short-term hibernating myocardium’. Short-term hibernating myocardium can respond to inotropic stimulation with increased contractile function, although at the expense of renewed worsening of the metabolic status. This occurrence of increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present. Significant involvement of adenosine and activation of ATP-dependent potassium channels have been excluded. The role of triggering events and acidosis is controversial. Short-term hibernating myocardium is, however, characterized by reduced calcium responsiveness. (Mol Cell Biochem 186: 185–193, 1998)

Key words

inotropic reserve ischemia myocardial metabolism myocardial hibernation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Rahimtoola SH: Coronary bypass surgery for chronic angina. Circulation 65: 225–241, 1982PubMedCrossRefGoogle Scholar
  2. 2.
    Rahimtoola SH: A perspective on the three large multicenter randomized clinical trials of coronary bypass surgery for chronic stable angina. Circulation 72(Suppl V): V-123-V-135, 1985Google Scholar
  3. 3.
    Vatner SF: Correlation between acute reductions in myocardial blood flow and function in conscious dogs. Circ Res 47: 201–207, 1980PubMedCrossRefGoogle Scholar
  4. 4.
    Weintraub WS, Hattori S, Agarwal JB, Bodenheimer MM, Banka VS, Heifant RH: The relationship between myocardial blood flow and contraction by myocardial layer in the canine left ventricle during ischemia. Circ Res 48: 430–438, 1981PubMedCrossRefGoogle Scholar
  5. 5.
    Gallagher KP, Matsuzaki M, Osakada G, Kemper WS, Ross Jr. J: Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis. Circ Res 52: 716–729, 1983PubMedCrossRefGoogle Scholar
  6. 6.
    Canty JM: Coronary pressure-function and steady-state pressure-flow relations during autoregulation in the unanesthetized dog. Circ Res 63: 821–836, 1988PubMedCrossRefGoogle Scholar
  7. 7.
    Heusch G: The relationship between regional blood flow and contractile function in normal, ischemic, and reperfused myocardium. Basic Res Cardiol 86: 197–218, 1991PubMedCrossRefGoogle Scholar
  8. 8.
    Ross Jr. J: Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation. Circulation 83: 1076–1083, 1991PubMedCrossRefGoogle Scholar
  9. 9.
    Matsuzaki M, Gallagher KP, Kemper WS, White F, Ross Jr. J: Sustained regional dysfunction produced by prolonged coronary stenosis: Gradual recovery after reperfusion. Circulation 68: 170–182, 1983PubMedCrossRefGoogle Scholar
  10. 10.
    Fedele FA, Gewirtz H, Capone RJ, Sharaf B, Most AS: Metabolic response to prolonged reduction of myocardial blood flow distal to a severe coronary artery stenosis. Circulation 78: 729–735, 1988PubMedCrossRefGoogle Scholar
  11. 11.
    Pantely GA, Malone SA, Rhen WS, Anselone CG, Arai A, Bristow J, Bristow JD: Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia. Circ Res 67: 1481–1493, 1990PubMedCrossRefGoogle Scholar
  12. 12.
    Braunwald E, Rutherford JD: Reversible ischemic left ventricular dysfunction: Evidence for the ‘hibernating myocardium’. J Am Coll Cardiol 8: 1467–1470, 1986PubMedCrossRefGoogle Scholar
  13. 13.
    Guth BD, Schulz R, Heusch G: Time course and mechanisms of contractile dysfunction during acute myocardial ischemia. Circulation 87(Suppl IV): IV35-IV42, 1993Google Scholar
  14. 14.
    Ross J Jr.: Mechanisms of regional ischemia and antianginal drug action during exercise. Prog Cardiovasc Dis 31: 455–466, 1989PubMedCrossRefGoogle Scholar
  15. 15.
    Schulz R, Rose J, Vahlhaus C, Post H, Backenköhler U, Heusch G: No maintenance of perfusion-contraction matching during 24 h sustained moderate myocardial ischemia in pigs. Faseb J, 1998Google Scholar
  16. 16.
    Downing SE, Chen V: Myocardial hibernation in the ischemic neonatal heart. Circ Res 66: 763–772, 1990PubMedCrossRefGoogle Scholar
  17. 17.
    Arai AE, Pantely GA, Anselone CG, Bristow J, Bristow JD: Active downregulation of myocardial energy requirements during prolonged moderate ischemia in swine. Circ Res 69: 1458–1469, 1991PubMedCrossRefGoogle Scholar
  18. 18.
    Downing SE, Chen V: Acute hibernation and reperfusion of the ischemic heart. Circulation 85: 699–707, 1992PubMedCrossRefGoogle Scholar
  19. 19.
    Schulz R, Guth BD, Pieper K, Martin C, Heusch G: Recruitment of an inotropic reserve in moderately ischemic myocardium at the expense of metabolic recovery: A model of short-term hibernation. Circ Res 70: 1282–1295, 1992PubMedCrossRefGoogle Scholar
  20. 20.
    Martin C, Schulz R, Rose J, Heusch G: Inorganic phosphate content and free energy change of ATP hydrolysis in regional short-term hibernating myocardium. Cardiovasc Res 1998, in pressGoogle Scholar
  21. 21.
    Heusch G, Rose J, Skyschally A, Post H, Schulz R: Calcium responsiveness in regional myocardial short-term hibernation and stunning in the in situ porcine heart — inotropic responses to post-extrasystolic potentiation and intracoronary calcium. Circulation 93: 1556–1566, 1996PubMedCrossRefGoogle Scholar
  22. 22.
    Schulz R, Rose J, Martin C, Brodde OE, Heusch G: Development of short-term myocardial hibernation: Its limitation by the severity of ischemia and inotropic stimulation. Circulation 88: 684–695, 1993PubMedCrossRefGoogle Scholar
  23. 23.
    Rose J, Schulz R, Martin C, Heusch G: Post-ejection wall thickening as a marker of successful short term hibernation. Cardiovasc Res 27: 1306–1311, 1993PubMedCrossRefGoogle Scholar
  24. 24.
    Schulz R, Rose J, Post H, Heusch G: Involvement of endogenous adenosine in ischemic preconditioning in swine. Pflügers Arch 430: 273–282, 1995PubMedCrossRefGoogle Scholar
  25. 25.
    Schulz R, Rose J, Post H, Heusch G: Regional short-term hibernation in swine does not involve endogenous adenosine or KATP channels. Am J Physiol 268: H2294–H3201, 1995PubMedGoogle Scholar
  26. 26.
    Schulz R, Rose J, Heusch G: Involvement of activation of ATP-dependent potassium channels in ischemic preconditioning in swine. Am J Physiol 267: H1341–H1352, 1994PubMedGoogle Scholar
  27. 27.
    Ferrari R, Cargnoni A, Bernocchi P, Pasini E, Curello S, Ceconi C, Ruigrok TJC: Metabolic adaptation during a sequence of no-flow and low-flow ischaemia: a possible trigger for hibernation. Circulation 94: 2587–2596, 1996PubMedCrossRefGoogle Scholar
  28. 28.
    van Binsbergen XA, van Emous JG, Ferrari R, van Echteid CJA, Ruigrok TJC: Metabolic and functional consequences of successive no-flow and sustained low-flow ischaemia; a 31P MRS study in rat hearts. J Mol Cell Cardiol 28: 2373–2381, 1996PubMedCrossRefGoogle Scholar
  29. 29.
    Schulz R, Post H, Sakka S, Wallbridge DR, Heusch G: Intraischemic preconditioning. Increased tolerance to sustained low-flow ischemia by a brief episode of no-flow ischemia without intermittent reperfusion. Circ Res 76: 942–950, 1995PubMedCrossRefGoogle Scholar
  30. 30.
    Arai AE, Grauer SE, Anselone CG, Pantely GA, Bristow JD: Metabolic adaptation to grandual reduction in myocardial blood flow. Circulation 92: 244–252, 1995PubMedCrossRefGoogle Scholar
  31. 31.
    Ito BR: Gradual onset of myocardial ischemia results in reduced myocardial infarction. Association with reduced contractile function and metabolic downregulation. Circulation 91: 2058–2070, 1995PubMedCrossRefGoogle Scholar
  32. 32.
    Kitakaze M, Marban E: Cellular mechanism of the modulation of contractile function by coronary perfusion pressure in ferret hearts. J Physiol 414: 455–472, 1989PubMedGoogle Scholar
  33. 33.
    Bolli R: Myocardial’ stunning’ in man. Circulation 86: 1671–1691, 1992PubMedCrossRefGoogle Scholar
  34. 34.
    Ambrosio G, Jacobus WE, Bergmann CA, Weisman HF, Becker LC: 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, 1987PubMedCrossRefGoogle Scholar
  35. 35.
    Arnold JMO, Braunwald E, Sandor T, Kloner RA: Inotropic stimulation of reperfused myocardium with dopamine: Effects on infarct size and myocardial function. J Am Coll Cardiol 6: 1036–1044, 1985CrossRefGoogle Scholar
  36. 36.
    Gorge G, Papageorgiou I, Lerch R: Epinephrine-stimulated contractile and metabolic reserve in postischemic rat myocardium. Basic Res Cardiol 85: 595–605, 1990PubMedCrossRefGoogle Scholar
  37. 37.
    Bolli R, Zhu W-X, Myers ML, Hartley CJ, Roberts R: Betaadrenergic stimulation reverses postischemic myocardial dysfunction without producing subsequent deterioration. Am J Cardiol 56: 964–968, 1985PubMedCrossRefGoogle Scholar
  38. 38.
    Bolukoglu H, Liedtke AJ, Nellis SH, Eggleston AM, Subramanian R, Renstrom B: An animal model of chronic coronary stenosis resulting in hibernating myocardium. Am J Physiol 263: H20–H29, 1992PubMedGoogle Scholar
  39. 39.
    Liedtke AJ, Renstrom B, Nellis SH, Subramanian R: Myocardial function and metabolism in pig hearts after relief from chronic partial coronary stenosis. Am J Physiol 267: H1312–H1319, 1994PubMedGoogle Scholar
  40. 40.
    Mills I, Fallon JT, Wrenn D, Sasken H, Gray W, Bier J, Levine D, Berman S, Gilson M, Gewirtz H: Adaptive responses of coronary circulation and myocardium to chronic reduction in perfusion pressure and flow. Am J Physiol 266: H447–H457, 1994PubMedGoogle Scholar
  41. 41.
    Chen C, Li L, Chen LL, Preda JV, Chen MH, Fallon ST, Weyman AE, Waters D, Gillam L: Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses. Circulation 92: 756–766, 1995PubMedCrossRefGoogle Scholar
  42. 42.
    Liedtke AJ, Renstrom B, Nellis SH, Hall JL, Stanley WC: Mechanical and metabolic functions in pig hearts after 4 days of chronic coronary stenosis. J Am Coll Cardiol 26: 815–828, 1995PubMedCrossRefGoogle Scholar
  43. 43.
    Shen Y-T, Vatner SF: Mechanism of impaired myocardial function during progressive coronary stenosis in conscious pigs. Hibernation versus stunning. Circ Res 76: 479–488, 1995PubMedCrossRefGoogle Scholar
  44. 44.
    Fallafollita JA, Perry BJ, Canty JM: 18F-2-deoxyglucose deposition and regional flow in pigs with chronically dysfunctional myocardium. Evidence for transmural variations in chronic hibernating myocardium. Circulation 95: 1900–1909, 1997CrossRefGoogle Scholar
  45. 45.
    Schulz R, Heusch G: Acute adaptation to ischemia: Short-term myocardial hibernation. Basic Res Cardiol 90: 29–31, 1995PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • Gerd Heusch
    • 1
  • Rainer Schulz
    • 1
  1. 1.Department of Pathophysiology, Centre of Internal MedicineUniversity of Essen School of MedicineEssenGermany

Personalised recommendations