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Alpha1-adrenergic blockade reduces exercise-induced regional myocardial ischemia in dogs

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Summary

The effect of selective α1-adrenoceptor blockade on regional myocardial blood flow and contractile function during exercise-induced myocardial ischemia was determined in nine dogs having chronic single vessel coronary stenosis (ameroid constrictor). Treadmill exercise performed after β-adrenoceptor blockade (1.0 mg/kg i.v. propranolol), to block potential prejunctional effects recently recognized with α-blockade, elicited severe regional myocardial ischemia with a steady-state reduction of regional systolic wall thickening of the post-stenotic myocardium from a resting value of 21.8% to 7.0%. Blood flow to the ischemic subendocardium was reduced from 0.76 to 0.36 ml/min/g (microspheres). Prazosin (80 μg/kg i.v.) was administered during continued running, and angiotensin II was simultaneously infused to prevent the decrease in systemic arterial pressure caused by prazosin. During the subsequent steady state, with arterial pressure matched to the pre-prazosin level, regional subendocardial blood flow improved to 0.60 ml/min/g and systolic wall thickening in the post-stenotic region increased modestly to 10.2%. No changes in blood flow to the outer portion of the post-stenotic region or the remote control region were seen, and prazosin caused no effect on regional function in the control area, indicating effective blockade of prejunctional effects of prazosin (demonstrated in pilot studies). The finding that blockade of α1-adrenoceptors resulted in improved ischemic zone subendocardial blood flow and contractile function are consistent with α1-adrenoceptor-mediated reduction of blood flow to the ischemic subendocardium during exercise-induced ischemia in dogs with β-blockade.

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References

  1. Aversano T, Becker LC (1985) Persistence of coronary vasodilator reserve despite functionally significant flow reduction. Am J Physiol 248:H403-H411

    Google Scholar 

  2. Bassenge E, Heusch G (1990) Endothelial and neuro-humoral control conorary blood flow in health and disease. Rev Physiol Biochem Pharmacol 116:77–165

    Google Scholar 

  3. Berkenboom GM, Abramowicz M, Vandermoten P, Degre SG (1986) Role of alpha-adrenergic coronary tone in exercise-induced angina pectoris. Am J Cardiol 57:195–198

    Google Scholar 

  4. Canty JM Jr., Klocke FJ (1985) Reduced regional myocardial perfusion in the presence of pharmacologic vasodilator reserve. Circulation 71:370–377

    Google Scholar 

  5. Chen DG, Dai X-Z, Bache RJ (1988) Post-synaptic adrenoceptor-mediated vasoconstriction in coronary and femoral vascular beds. Am J Physiol 254:H984-H992

    Google Scholar 

  6. Chen DG, Dai X-Z, Zimmerman BG, Bache RJ (1988) Post-synaptic alpha 1 and alpha 2-adrenergic mechanisms in coronary vasoconstriction. J Cardiovasc Pharmacol 11:61–67

    Google Scholar 

  7. Chilian WM, Harrison DG, Haws CW, Snyder WD, Marcus ML (1986) Adrenergic coronary tone during submaximal exercise in the dog is produced by circulating catecholamines. Evidence for adrenergic denervation supersensitivity in the myocardium but not in coronary vessels. Circ Res 58:68–82

    Google Scholar 

  8. Chilian WM, Ackell PH (1988) Transmural differences in sympathetic coronary constriction during exercise in the presence of coronary stenosis. Circ Res 62:216–225

    Google Scholar 

  9. Deussen A, Heusch G, Thämer V (1985) α1-Adrenoceptor-mediated coronary vasoconstriction persists after exhaustion of coronary dilator reserve. Eur J Pharmacol 115:147–153

    Google Scholar 

  10. Feigl EO (1983) Coronary physiology. Physiol Rev 63:1–205

    Google Scholar 

  11. Gallagher KP, Osakada G, Matsuzaki M, Kemper WS, Ross J Jr (1982) Myocardial blood flow and function with critical coronary stenosis in exercising dogs. Am J Physiol 243:H698-H707

    Google Scholar 

  12. Gothert M, Kollecker P (1986) Subendothelial beta2-adrenoreceptors in the rat vena cava: facilitation of noradrenaline release via local stimulation of angiotensin II synthesis. Naunyn-Schmiedebergs Archives of Pharmacology 334:156–165

    Google Scholar 

  13. Gwirtz PA, Overn SP, Mass HJ, Jones CE (1986) α1-Adrenergic constriction limits coronary flow and cardiac function in running dogs. Am J Physiol 250:H1117-H1126

    Google Scholar 

  14. Guth BD, Thaulow E, Heusch G, Seitelberger R, Ross J Jr (1990) Myocardial effects of selective alpha-adrenoceptor blockade during exercise in dogs. Circ Res 66:1703–1712

    Google Scholar 

  15. Guth BD, Heush G, Seitelberger R, Ross J Jr (1987) Elimination of exercise-induced regional myocardial dysfunction by a bradycardic agent in dogs with chronic coronary stenosis. Circulation 75:661–669

    Google Scholar 

  16. Harrison DG, Chilian WM, Marcus ML (1986) Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals. Circ Res 59:133–142

    Google Scholar 

  17. Heusch G, Guth BD, Seitelberger R, Ross J Jr (1987) Attenuation of exercise-induced myocardial ischemia by recruitment of coronary vasodilator reserve with nifedipine. Circulation 75:482–492

    Google Scholar 

  18. Heusch G, Deussen A, Schipke J, Thämer V (1984) α1- and α1-adrenoceptor mediated vasoconstriction of large and small caninc coronary arteries in vivo. J Cardiovasc Pharmacol 6:961–968

    Google Scholar 

  19. Heusch G, Deussen A (1983) The effects of cardiac sympathetic nerve stimulation on perfusion of stenotic coronary arteries in the dog. Circ Res 53:8–15

    Google Scholar 

  20. Heusch G, Deussen A, Thämer V (1985) Cardiac sympathetic nerve activity and progressive vasoconstriction distal to coronary stenoses: Feed-back aggravation of myocardial ischemia. J Auton Nerv Syst 13:311–326

    Google Scholar 

  21. Heyndrickx GR, Muylaert P, Pannier JL (1982) Alpha-adrenergic control of oxygen delivery to myocardium during exercise in conscious dogs. Am J Physiol 242:H805-H809

    Google Scholar 

  22. Holtz J, Saeed M, Sommer O, Bassenge E (1982) Norepinephrine constricts the canine coronary bed via post-synaptic α2-adrenoceptors. Eur J Pharmacol 82:199–202

    Google Scholar 

  23. Holtz J, Mayer E, Bassenge E (1977) Demonstration of alpha-adrenergic coronary control in different layers of canine myocardium by regional myocardial sympathectomy. Pfluegers Arch 372:187–194

    Google Scholar 

  24. Laxson DD, Dai X-Z, Homans DC, Bache RJ (1989) The role of alpha 1- and alpha 2-adrenergic receptors in mediation of coronary vasoconstriction in hypoperfused ischemic myocardium during exercise. Circ Res 65:1688–1697

    Google Scholar 

  25. Laxson DD, Dai X-Z, Homans DC, Bache RJ (1992) Coronary vasodilator reserve in ischemic myocardium of the exercising dog. Circulation 85:313–322

    Google Scholar 

  26. Liang IYS, Jones CE (1985) α1-Adrenergic blockade increases coronary blood flow during coronary hypoperfusion. Am J Physiol 249:H1070-H1077

    Google Scholar 

  27. Maruoka Y, McKirnan MD, Engler RL, Longhurst JC (1987) Functional significance of α-adrenergic receptors in mature coronary collateral circulation of dogs. Am J Physiol 253:H582-H590

    Google Scholar 

  28. Matsuzaki M, Patritti J, Tajimi T, Miller M, Kemper WS, Ross J Jr (1984) Effects of beta-blockade on regional myocardial flow and function during exercise. Am J Physiol 16:H52-H60

    Google Scholar 

  29. Miyamoto MI, Rockman HA, Guth BD, Heusch G, Ross J Jr (1991) The effect of alpha-adrenergic stimulation on regional contractile function and myocardial blood flow with and without ischemia. Circulation 84:1715–1724

    Google Scholar 

  30. Murray PA, Vatner SF (1979) α-Adrenoceptor attenuation of the coronary vascular response to severe exercise in the conscious dog. Circ Res 45:654–660

    Google Scholar 

  31. Nathan HJ, Feigl EO (1986) Adrenergic vasoconstriction lessens transmural steal during coronary hypoperfusion. Am J Physiol 250:H645-H653

    Google Scholar 

  32. Pantely GA, Bristow JD, Swenson LJ, Ladley HD, Johnson WB, Anselone CG (1985) Incomplete coronary vasodilation during myocardial ischemia in swine. Am J Physiol 249:H638-H647

    Google Scholar 

  33. Ross J Jr, Gallagher KP, Matsuzaki M, Lee JD, Guth BD, Goldfarb R (1986) Regional myocardial blood flow and function in experimental myocardial ischemia. Can J Cardiol 2 (Suppl A): 9A-18A

    Google Scholar 

  34. Ross J Jr (1989) Mechanisms of regional ischemia and antianginal drug action during exercise. Prog Cardiovasc Dis 31:455–466

    Google Scholar 

  35. Seitelberger R, Guth BD, Heusch G, Lee JD, Katayama K, Ross J Jr (1988) Intracoronary alpha2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise. Circ Res 62:436–442

    Google Scholar 

  36. Seitelberger R, Guth BD, Heusch G, Ross J Jr (1991) Alpha2-adrenergic coronary constriction in ischemic myocardium during exercise. In: Heusch G, Ross J Jr (eds) Adrenergic mechanisms in myocardial ischemia. Steinkopff Verlag, Darmstadt; Springer-Verlag, New York, pp 207–217

    Google Scholar 

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Author notes

  1. B. D. Guth & G. Heusch

    Present address: Abteilung für Pathophysiologie, Universitätsklinikum Essen, Hufelandstraße 55, 4300, Essen, Germany

  2. T. Miura

    Present address: Yamaguchi University, Ube, Japan

  3. E. Thaulow

    Present address: Ulleval Sykehus, Dept. of Clinical Physiology, University Hospital, Rikshospitalet, 0027, Oslo 1, Norway

  4. John Ross Jr.

    Present address: Division of Cardiology, Department of Medicine, University of California, San Diego, 92093, La Jolla, CA, USA

Authors and Affiliations

  1. Seaweed Canyon Laboratory, Department of Medicine, University of California, San Diego, La Jolla, California, USA

    B. D. Guth, T. Miura, E. Thaulow, G. Heusch & John Ross Jr.

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  1. B. D. Guth
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  2. T. Miura
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  3. E. Thaulow
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  4. G. Heusch
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  5. John Ross Jr.
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Additional information

Supported by National Institutes of Health Research Grant HL-17682, Ischemic Heart Disease Specialized Center of Research (SCOR) awarded by the National Heart, Lung and Blood Institute, Bethesda, MD.

During these studies, Dr. Thaulow was the recipient of a research fellowship granted by the Fogarty International Center Grant 1F05 TWO3753-01 BI-5 (12).

Prof. Dr. E. Bassenge served as guest editor for this manuscript and was responsible for all editorial decisions, including the selection of reviewers. This policy applies to all manuscripts with authors from the editor's institution.

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Guth, B.D., Miura, T., Thaulow, E. et al. Alpha1-adrenergic blockade reduces exercise-induced regional myocardial ischemia in dogs. Basic Res Cardiol 88, 282–296 (1993). https://doi.org/10.1007/BF00795000

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  • DOI: https://doi.org/10.1007/BF00795000

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