Summary
The effect of recurrent periods of ischemia on the myocardium was investigated in 15 open-chest dogs. Ischemia was produced by 3 minutes of proximal occlusion of the left anterior descending coronary artery. Each occlusion was followed by reperfusion of 3 minutes duration. Forty occlusions with a total of 120 minutes of ischemia were performed, and regional function (sonomicrometry) as well as high energy phosphates (needle biopsies) were determined at the end of the 5th, 20th, and 40th period of ischemia and reperfusion. The first periods of ischemia had a cumulative effect both on regional postischemic function (44% and 59% respectively of preischemic control after 20 occlusions) and on the ATP content, but with increasing number of occlusions the additive effects became smaller (ATP reduction/μmol/gww/per occlusion). The ATP breakdown per occlusion was diminished with increasing number of periods of ischemia, and no significant adenosine was measured in the ischemic myocardium. Higher than normal postischemic creatine phosphate levels (9.1 μmol/g w w at the 40th reperfusion vs. 6.7 μmol/gw w control) indicated a functioning oxidative phosphorylation in the presence of an ATP utilization problem at the sarcomere level, because indicators of the cellular energy level (energy charge, free energy change of ATP hydrolysis) quickly normalized during reperfusion. Stunned myocardium is therefore not a problem of energy supply but rather of energy utilization. Reduced ATP utilization and regional dysfunction are the expressions of the same cellular defect which resides either in the ATP-splitting contractile apparatus or in the electromechanical coupling. Contractile dysfunction during reperfusion protects the heart against subsequent periods of ischemia because ATP turnover is reduced.
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References
Atkinson DE (1968) The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 11:4030–4031
Braunwald E, Kloner RA (1982) The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation 66:1146–1149
Brazzamano S, Fedor JM, Rembert JC, Greenfield Jr JC (1984) Increase in myocardial collateral blood flow during repeated brief episodes of ischemia in the awake dog. Basic Res Cardiol 79:448–453
Bretschneider HJ, Cott LA, Hensel I, Kettler D, Martel J (1970) Ein ncuer komplexer haemodynamischer Parameter aus 5 additiven Gliedern zur Bestimmung des O2-Bedarfs des linken Ventrikels. Pflügers Arch ges Physiol 319:14
DeBoer LWV, Ingwall JS, Kloner RA, Braunwald E (1980) Prolonged derangements of canine myocardial purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis. Proc Natl Acad Sci USA 77:5471–5475
Geft IL, Fishbein MC, Ninomiya K, Hashida J, Chaux E, Yano J, Y-Rit J, Genov T, Shell W, Ganz W (1982) Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis. Circulation 66:1150–1160
Gerlach E, Deuticke B, Dreisbach RH (1963) Der Nukleotidabbau im Herzmuskel bei Sauerstoffmangel und seine mögliche Bedeutung für die Koronardurchblutung. Naturwissenschaft 50:228–229
Giesen J, Kammermeier H (1980) Relationship of phosphorylation potential and oxygen consumption in isolated perfused rat hearts. J Mol Cell Cardiol 12:891–907
Glower DD, Hoffmeister M, Newton JR, Wolfe JA, Spratt JA, Tyson GS, Swain JL, Rankin JS (1983) Relationship between altered diastolic properties and systolic function after reversible ischemic injury. Circulation 68 (Supp III):III-253
Hagl S, Heimisch W, Meisner H, Erben R, Baum M, Mendler N (1977) The effect of hemodilution on regional myocardial function in the presence of coronary stenosis. Basic Res Cardiol 72:344–364
Hearse DJ (1979) Oxygen deprivation and early myocardial contractile failure: A reassessment of the possible role of adenosine triphosphate. Am J Cardiol 44:1115–1121
Heyndrickx GR, Millard RW, McRitchie RJ, Maroko PR, Vatner SF (1975) Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest 56:978–985
Hoffmeister HM, Mauser M, Schaper W (1985) Effect of adenosine and AICAR on ATP content and regional contractile function in reperfused canine myocardium. Basic Res Cardiol 80:445–458
Ito BR, Tate H, Schaper W (1985) Regional mycocardial function and oxygen consumption following transient coronary artery occlusion in the dog. Z. Kardiol 74:243 (abstr)
Kahles H, Mezger VA, Korb H, Hellige B, Bretschneider HJ (1983) A new model for testing therapeutic interventions during myocardial ischemia. Res Exp Med (Berl) 182:149–152
Kammermeier H, Schmidt P, Jüngling E (1982) Free energy change of ATP-hydrolysis: a causal factor of early hypoxic failure of the myocardium? J Mol Cell Cardiol 14:267–277
Klein HH, Puschmann S, Schaper J, Schaper W (1981) The mechanism of the tetrazolium reaction in identifying experimental myocardial infarction. Virchows Arch (Pathol Anat) 393:287–297
Kloner RA, DeBoer LWV, Darsee JR, Ingwall JS, Hale S, Tumas J, Braunwald E (1981) Prolonged abnormalities of myocardium salvaged by reperfusion. Am J Physiol 241:H591-H599
Kübler W, Katz AM (1977) Mechanism of early “pump” failure of the ischemic heart: possible role of adenosine triphosphate depletion and inorganic phosphate accumulation. Am J Cardiol 40:467–471
Lange R, Ingwall JS, Hale SL, Alker KJ, Kloner RA (1984) Effects of recurrent ischemia on myocardial high energy phosphate content in canine hearts. Basic Res Cardiol 79:469–478
Lange R, Ware J, Kloner RA (1984) Absence of a cumulative deterioration of regional function during three repeated 5 or 15 minute coronary occlusions. Circulation 69:400–408
Mauser M, Hoffmeister HM, Nienaber C, Schaper W (1985) Influence of ribose, adenosine and AICAR on the rate of myocardial tissue ATP synthesis during reperfusion after coronary artery occlusion in the dog. Circ Res 56:220–230
Murry CE, Reimer KA, Long JB, Jennings RB (1985) Preconditions with ischemia protects ischemic myocardium. Circulation 72 (Suppl III): 475 (abstr)
Neely JR, Rovetto MJ, Whitmer JT, Morgan HE (1973) Effects of ischemia on function and metabolism of the isolated working rat heart. Am J Physiol 225:651–658
Nishioka K, Jarmakain JM (1982) Effect of ischemia on mechanical function and high-energy phosphates in rabbit myocardium. Am J Physiol 242:H1077-H1083
Ohara H, Kanaide H, Yoshimura R, Okada M, Nakamura M (1981) A protective effect of coenzyme Q10 on ischemia and reperfusion of the isolated perfused rat heart. J Mol Cell Cardiol 13:65–74
Pasque MK, Spray TL, Pellom GL, Trigt P van, Peyton RB, Currie WD, Wechsler AS (1982) Ribose-enhanced myocardial recovery following ischemia in the isolated working rat heart. J Thorac Cardiovasc Surg 83:390–398
Reibel DK, Rovetto MJ (1978) Myocardial ATP synthesis and mechanical function following oxygen deficiency. Am J Physiol 234:H620-H624
Reimer KA, 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
Saks VA, Kupriyanov VV, Elizarova GV (1980) Studies of energy transport in heart cells. J Biol Chem 255:755–763
Sasayama S, Osakada G, Takahashi M, Shimada T, Kawai C (1980) Modification of regional function of ischaemic myocardium by the alteration of arterial pressure in dogs. Cardiovasc Res 14:93–102
Savabi F, Geiger PJ, Bessman SP (1984) Myofibrillar end of the creatine phosphate energy shuttle. Am J Physiol (Cell Physiol) 247:424–432
Schaper J, Mulch J, Winkler B, Schaper W (1979) Ultrastructural, functional, and biochemical criteria for estimation of reversibility of ischemic injury. A study on the effects of global ischemia on the isolated dog heart. J Mol Cell Cardiol 11:521–541
Schaper W, Frenzel H, Hort W (1979) Experimental coronary artery occlusion. I. Measurement of infarct size. Basic Res Cardiol 74:46–53
Schrader J (1981) Sites of action and production of adenosine in the heart. In: Burnstock G (ed) Purinergic Receptors. Chapman and Hall. London, pp. 121–162
Vial C, Crozatier B, Boldschmidt D, Fond B (1982) Adenine nucleotide content and regional function during ischemia and reperfusion in canine ventricular myocardium. Basic Res Cardiol 77:645–655
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Hoffmeister, H.M., Mauser, M. & Schaper, W. Repeated short periods of regional myocardial ischemia: effect on local function and high energy phosphate levels. Basic Res Cardiol 81, 361–372 (1986). https://doi.org/10.1007/BF01907457
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DOI: https://doi.org/10.1007/BF01907457