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Mechanisms of pain in angina pectoris—A critical review of the adenosine hypothesis

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Summary

Clinical characteristics: Angina pectoris represents a visceral pain caused by reversible myocardial ischemia. The majority of ischemic attacks are symptomless. When pain is manifested, it appears late during the ischemic event. The pain is complex in its quality and bears little relation to the region of myocardial ischemia. Pain shows a sensitive dependence on initial conditions suggesting a mechanism with deterministic chaotic dynamics for the association between myocardial ischemia and pain.Neurophysiological substrate: Ganglia are present within the heart, particularly in epicardial fat. The blood supply of intrinsic cardiac ganglia arises primarily from branches of the proximal coronary arteries. Both afferent and efferent neurons within the intrinsic cardiac nervous system exist, while the majority of neurons in that location may be local circuit neurons. Integration takes place not only in the intrinsic cardiac nervous system, but also in mediastinal, middle cervical, and stellate ganglia. Cardiac afferent receptors are also connected to cell bodies in dorsal root and nodose ganglia, as well as intrathoracic ganglia. Myocardial regions have no spatial representation in these ganglia. Adenosine, among a number of substances, can modulate the activity generated by cardiac afferent nerve endings and intrinsic cardiac neurons. Such effects appear to be exerted at A1 receptors.Adenosine as a pain messenger: During myocardial ischemia adenosine is released in large quantities into the interstitial space. The endothelium takes up the major amount of adenosine. Thus only small increments of adenosine are detected in the blood-stream. Given as an intravenous bolus to healthy volunteers or to patients with ischemic heart disease and angina pectoris, adenosine provokes angina pectorislike pain, which is similar to habitual angina pectoris with regard to quality and location. Pain is provoked in the absence of ECG signs of ischemia. Patients with asymptomatic myocardial ischemia are less sensitive to adenosine, whereas patients with Syndrome X are more sensitive with respect to adenosine-provoked pain. When adenosine is given intraarterially, including into the coronary arteries, pain is provoked in the corresponding vascular bed. Adenosine-provoked pain and ischemic pain are counteracted by previous administration of the adenosine receptor antagonist theophylline. Adenosine-provoked pain is enhanced by nicotine or substance P.Conclusion: Angina pectoris displays complex characteristics at both the clinical and neural substrate levels. Adenosine is the only candidate substance identified that fulfills criteria for a messenger between myocardial ischemia and the genesis of pain. It is concluded that ischemically released adenosine causes specific spatiotemporal neural summation of afferent neuronal activity, which elicits an alarm reaction with manifestation of pain.

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References

  • Abood LG. Neuronal metabolism. In: Field, ed.Handbook of Physiology, Sect J, Neurophysiology, American Physiological Society, Washington DC, 1960:1815–1826.

    Google Scholar 

  • Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD.Molecular Biology of the Cell. New York: Garland Publishing, 1989.

    Google Scholar 

  • Ardell JL, Butler CK, Smith FM, Hopkins DA, Armour JA. Activity of in vivo atrial and ventricular neurons in chronically decentralized canine hearts.Am J Physiol 1991;260:H713-H721.

    Google Scholar 

  • Areskog NH, Adolfsson L. Effects of a cardio-selective beta-adrenergic blocker (ICI 50172) at exercise in angina pectoris.Br Med J 1969;II:601–630.

    Google Scholar 

  • Armour JA. Anatomy and function of the intrathoracic neurons regulating the mammalian heart. In: Zucker IH, Gilmore JP, eds.Reflex Control of the Circulation. Boca Raton, FL: CRC Press, 1991:1–37.

    Google Scholar 

  • Armour JA, Hopkins DA. Activity of canine in situ left atrial ganglion neurons.Am J Physiol 1990a;259:H1207-H1215.

    Google Scholar 

  • Armour JA, Hopkins DA. Activity of in vivo canine ventricular neurons.Am J Physiol 1990b;258:H326-H336.

    Google Scholar 

  • Armour JA, Yuan BX, Butler CK. Cardiac responses elicited by peptides administered to canine intrinsic cardiac neurons.Peptides 1990;11:753–761.

    Google Scholar 

  • Armour JA, Huang MH, Pelleg A, Sylvén C. Activity of in situ canine nodose ganglion cardiac afferent neurons responsive to mechanoreceptor and/or chemoreceptor inputs.Cardiovasc Res 1993;27: submitted.

  • Azam F, Hudson RE. Dissolved ATP in the sea and its utilisation by marine bacteria.Nature 1977;267:696–698.

    Google Scholar 

  • Belloni FL, Belardinelli L, Halperne C, Hintze T. An unusual receptor mediates adenosine-induced SA nodal bradycardia in dogs.Am J Physiol 1989;256:H1553-H1564.

    Google Scholar 

  • Berne RM. Cardiac nucleotides in hypoxia: Possible role in regulation of coronary blood flow.Am J Physiol 1963;204:317–322.

    Google Scholar 

  • Biaggioni I, Killian TJ, Mosqueda-Garcia R, Robertson RM, Robertson D. Adenosine increases sympathetic nerve traffic in humans.Circulation 1991;83:1668–1675.

    Google Scholar 

  • Bleehen T, Keele CA. Observations on the algogenic actions of adenosine compounds on the human blister base preparation.Pain 1977;3:367–377.

    Google Scholar 

  • von Borstel RW, Renshaw AA, Wurtman RJ. Adenosine strongly potentiates pressor responses to nicotine in rats.Proc Natl Acad Sci USA 1984;81:5599–5603.

    Google Scholar 

  • von Borstel RW, Evoniuk GE, Wurtman RJ. Adenosine potentiates sympathomimetic effects of nicotinic agonists in vivo.Pharmacol Exp Ther 1986;236:344–349.

    Google Scholar 

  • Bunch FT, Thornton J, Cohen MV, Downey JM. Adenosine is an endogenous protectant against stunning during repetitive ischemic episodes in the heart.Am Heart J 1992;124:1440–1446.

    Google Scholar 

  • Burnstock G. Overview (purinergic receptors). In: Imai S, Nakazawa M, eds.Role of Adenosine and Adenine Nucleotides in the Biological System. Amsterdam: Elsevier, 1991:3–16.

    Google Scholar 

  • Butler CK, Smith FM, Cardinal R, Murphy DA, Hopkins DA, Armour JA. Cardiac responses to electrical stimulation of discrete loci in canine atrial and ventricular ganglionated plexi.Am J Physiol 1990;259:H1365-H1373.

    Google Scholar 

  • Campbell JN, Raja SN, Cohen RH, Manning DC, Khan AA, Meyer RA. Peripheral mechanisms of nociception. In: PD Wall and R Melzack (eds.)Textbook of Pain, Churchill-Livingstone,2nd ed., 1989:22–45.

  • Cannon RO, Quyyumi A, Schenke WH, et al. Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries.J Am Coll Cardiol 1990;16:1359–1366.

    Google Scholar 

  • Collins P, Fox KM. Pathophysiology of angina.Lancet 1990;335:94–96.

    Google Scholar 

  • Costa F, Angel M, Biaggioni I. Adenosine acts locally in forearm to increase sympathetic nerve traffic in humans. Circulation 1992;86(Suppl I):I368.

    Google Scholar 

  • Cox DA, Vita JA, Treasure CB, Fish RD, Selwyn AP, Ganz P. Reflex increase in blood pressure during the intracoronary administration of adenosine in man.J Clin Invest 1989;84:592–596.

    Google Scholar 

  • Crea F, Galassi AR, Kaski JC, et al. Effect of theophylline on exercise-induced myocardial ischaemia.Lancet 1989;8640:683–686.

    Google Scholar 

  • Crea F, Pupita G, Galassi AR, et al. Role of adenosine in pathogenesis of anginal pain.Circulation 1990;81,1:165–173.

    Google Scholar 

  • Crea F, Gaspardone A, Kaski JC, Davies G, Maseri A. Relation between stimulation site of cardiac afferent nerves by adenosine and distribution of cardiac pain: Results of a study in patients with stable angina.J Am Coll Cardiol 1992;20:1498–1502.

    Google Scholar 

  • Cronstein BN, Kramer SB, Rosenstein ED, Weissman G, Hirschhorn R. Adenosine modulates the generation of superoxide anion by stimulated human neutrophils via interaction with a specific cell surface receptor.Ann NY Acad Sci 1985;451:291–301.

    Google Scholar 

  • Dibner-Dunlap, ME, Kinugawa T, Thames MD. Intracoronary adenosine activates cardiac sympathetic afferents via stimulation of A1 receptors (abstract).Circulation 1992;86(Suppl I):I638.

    Google Scholar 

  • Dickensson AH. Mechanisms of the analgesic actions of opiates and opioids.Br Med Bull 1991;47:690–702.

    Google Scholar 

  • Drake-Holland A, Noble MIM. Cellular abnormalities in chronically denervated myocardium. Implications for the transplanted heart.Circulation 1989;80:1476–1481.

    Google Scholar 

  • Droste C. Schmerzperzeption und periphere schmerz-lokalisation bei angina pectoris.Z Kardiol 1988;77(Suppl 5):15–33.

    Google Scholar 

  • Droste C, Greenlee MW, Roskamm H. A defective angina pectoris pain warning system: Experimental findings of ischemic and electrical pain test.Pain 1986;26:199–209.

    Google Scholar 

  • Drury AM, Szent-Györgyi A. The physiological activity of adenine compounds with special reference to their action upon the mammalian heart.J Physiol 1929;68:213–239.

    Google Scholar 

  • Edlund A, Fredholm BB, Patrignani P, Patrono D, Wennmalm Å, Wennmalm M. Release of two vasodilators—adenosine and prostacyclin—from isolated rabbit heart during controlled hypoxia.J Physiol (Lond) 1983;340:487–501.

    Google Scholar 

  • Edlund A, Berglund B, Van Dorne D, et al. Coronary flow regulation in patients with ischemic heart disease: Release of purines and prostacyclin from the ischemic human heart.Circulation 1985;71:1113–1120.

    Google Scholar 

  • Eldar M, Hollander G, Schulhoff N, et al. Bradykinin level in the great cardiac vein during balloon angioplasty of the left anterior descending coronary artery.Am J Cardiol 1992;70:1621–1623.

    Google Scholar 

  • Englestein ED, Somers V, Clary MP, Leman BB, Rea RF. Endogenous adenosine uptake inhibition increases muscle sympathetic nerve activity in conscious humans.Circulation 1992;86(Suppl I):I368.

    Google Scholar 

  • Engler RL, Gruber HE. Adenosine an autacoid. In: Fozzard H, Haber E, Jennings RB, et al., eds.The Heart and Cardiovascular System, 2nd ed. New York: Raven Press, 1991:1745–1764.

    Google Scholar 

  • Eriksson B, Vuorisalo D, Sylvén C. Quality and intensity of chest pains in patients treated in coronary care.Pain 1993, in press.

  • Evoniuk GE, von Borstel RW, Wurtman RJ. Adenosine affects sympathetic neurotransmission at multiple sites in vivo.J Pharmacol Exp Ther 1986;236:350–355.

    Google Scholar 

  • Feldman MD, Ayers CR, Lehman MR, et al. Improved detection of ischemia-induced increases in coronary sinus adenosine in patients with coronary artery disease.Clin Chem 1992;38:256–262.

    Google Scholar 

  • Franco-Cereceda A, Saria A, Lundberg JM. Differential release of calcitonin gene-related peptide and neuropeptide Y from the isolated heart by capsaicin, ischaemia, nicotine, bradykinin and ouabain.Acta Physiol Scand 1989;135:173–187.

    Google Scholar 

  • Fredholm BB, Sollevi A. Cardiovascular effects of adenosine.Clin Physiol 1986;6:1–21.

    Google Scholar 

  • Fuller RW, Maxwell DL, Conradson R-B, Dixon CMS, Barnes PJ. Circulatory and respiratory effects of infused adenosine in conscious man.Br J Clin Pharmacol 1987;24:306–317.

    Google Scholar 

  • Furchgott RF. The role of endothelium in the responsive vascular smooth muscle to drugs.Ann Rev Pharmacol 1984;24:175–197.

    Google Scholar 

  • Gaspardone A, Crea F, Tomai F, et al. Algogenic effects of the intrafemoral infusion of adenosine (abst)J Am Coll Cardiol 1992a;19:330a.

  • Gaspardone A, Crea F, Tomai F, et al. Substance P facilitates adenosine-induced pain (abstract).Eur Heart J 1992b;13(Suppl):363.

    Google Scholar 

  • Gaspardone A, Crea F, Iamele M, et al. Bamiphylline improves exercise-induced myocardial ischemia through a novel mechanism of action.Circulation 1993;88:502–508.

    Google Scholar 

  • Glover WE, Roddie IC, Shanks RG. The effect of intraarterial potassium chloride infusions on vascular reactivity in the human forearm.J Physiol (Lond) 1962;163:22P-23P.

    Google Scholar 

  • Gustafsson LE, Wiklund NP. Adenosine modulation of cholinergic and non-adrenergic non-cholinergic neurotransmission in the rabbit iris sphincter.Br J Pharmacol 1986a;88:197–204.

    Google Scholar 

  • Gustafsson LE, Wiklund NP, Cederqvist B. Apparent enhancement of cholinergic transmission in rabbit bronchi via adenosine A2 receptors.Eur J Pharmacol 1986b;120:179–185.

    Google Scholar 

  • Gustafsson LE, Wiklund NP, Lundin J, Hedqvist P. Characterisation of pre- and post-junctional adenosine receptors in guinea-pig ileum.Acta Physiol Scand 1985;123:195–203.

    Google Scholar 

  • Haneda T, Ichihara K, Abiko Y, Onodera S. Release of adenosine and lactate from human hearts during atrial pacing in patients with ischemic heart disease.Clin Cardiol 1989;12:76–82.

    Google Scholar 

  • Heberdeen W. Some account of a disorder of the breast.Med Trans 1772;2:59–67.

    Google Scholar 

  • Hedner T, Hedner J, Wessberg P, Jonason J. Regulation of breathing in the rat: Indications for a role of central adenosine mechanisms.Neurosci Lett 1982;33:147–151.

    Google Scholar 

  • Hillarp NÅ. Peripheral autonomic mechanisms. In: Field J, ed.Handbook of Physiology, Sect 1. Neurophysiology. American Physiology Society, Washington, DC: 1960:979–1006.

    Google Scholar 

  • Holgate ST, Finnerty JP, Polosa R. Mechanisms of purine-induced bronchoconstriction in asthma.Arch Int Pharmacodyn Ther 1990;303:122–131.

    Google Scholar 

  • Hopkins DA, Armour JA. Ganglionic distribution of afferent neurons innervating the canine heart and cardiopulmonary nerves.J Auton Nerv Syst 1989;26:213–222.

    Google Scholar 

  • Huang MH, Smith FM, Armour JA. Amino acids modify the activity of canine intrinsic cardiac neurons involved in cardiac regulation.Am J Physiol 1993a;264:H1275-H1282.

    Google Scholar 

  • Huang MH, Sylvén C, Smith FM, Pelleg A, Armour JA. Adenosine and adenosine 5-triphosphate modulate intrinsic cardiac neuronal activity in the dog.Am J Physiol 1993b, in press.

  • Janes RD, Brandys JC, Hopkins DA, Johnstone DE, Murphy DA, Armour JA. Anatomy of human extrinsic cardiac nerves and ganglia.Am J Cardiol 1986;57:299–309.

    Google Scholar 

  • Jonzon B, Fredholm BB. Adenosine receptor mediated inhibition of noradrenaline release from slices of rat hippocampus.Life Sci 1984;35:1971–1979.

    Google Scholar 

  • Jonzon B, Bergquist A, Li YO, Fredholm BB. Effects of adenosine and two stable adenosine analogues on blood pressure, heart rate and colonic temperature in the rat.Åcta Physiol Scand 1986;126:491–498.

    Google Scholar 

  • Jonzon B, Sylvén C, Kaijser L. Theophylline decreases pain in the ischaemic forearm test.Cardiovasc Res 1989;23:807–809.

    Google Scholar 

  • Kannel WB, Abbott RD. Incidence and prognosis of unrecognized myocardial infarction. An up-date on the Framingham study.N Engl J Med 1984;311:1144–1147.

    Google Scholar 

  • Katholi RE, McCann WP, Woods WT. Intrarenal adenosine produces hypertension via renal nerves in the one-kidney, one clip rat.Hypertension 1985;7(Suppl I):188–193.

    Google Scholar 

  • Keefer CS, Resnik WH. Angina pectoris; a syndrome caused by anoxemia of the myocardium.Arch Intern Med 1928;41:769–807.

    Google Scholar 

  • Keele CA, Armstrong D. Substances producing pain and itch. In: Barcroft H, Dawson H, Paton, WDM, eds.Monographs of the Physiological Society, No. 12. London: Arnold, 1964:89–106.

    Google Scholar 

  • Kitakaze M, Hori M, Sato H, Takashima S, Kitabatake A. Endogenous adenosine inhibits formation microthromboembolism in ischemic myocardium.Circulation 1990;82(Suppl III):III276.

    Google Scholar 

  • Kleber AG. Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts.Circ Res 1983;52:442–450.

    Google Scholar 

  • Klement W, Arndt JO. Adenosine does not evoke pain from venous and paravascular nociceptors in the human.Cardiovasc Res 1992;26:186–189.

    Google Scholar 

  • Lagerqvist B, Sylvén C, Hedenström H, Waldenström A. Intravenous adenosine but not its first metabolite inosine provokes chest pain in healthy volunteers.J Cardiovasc Pharmacol 1990a;16:173–176.

    Google Scholar 

  • Lagerqvist B, Sylvén C, Helmius G, Waldenström A. Effects of exogenous adenosine in a patient with transplanted heart. Evidence for adenosine as a messenger in angina pectoris.Upsala J Med Sci 1990b;95:137–145.

    Google Scholar 

  • Lagerqvist B, Sylvén C, Beermann B, Helmius G, Waldenström A. Intracoronary adenosine causes angina pectoris like pain—an inquiry into the nature of visceral pain.Cardiovasc Res 1990c;24:609–613.

    Google Scholar 

  • Lagerqvist B, Sylvén C, Theodorsen E, Kaijser L, Helmius G, Waldenström A. Adenosine induced chest pain—a comparison between intracoronary bolus injection and steady state infusion.Cardiovasc Res 1992a;26:810–814.

    Google Scholar 

  • Lagerqvist B, Sylvén C, Waldenström A. Low threshold for adenosine induced chest pain in patients with angina pectoris and normal coronary angiogram.Br Heart J 1992b;68:282–283.

    Google Scholar 

  • Lagerqvist B, Bylund H, Götell P, Mannting F, Sandhagen B, Waldenström A. Coronary artery vasoregulation and left ventricular function in patients with angina pectoris-like pain and normal coronary angiograms.J Intern Med 1991;230:55–65.

    Google Scholar 

  • Laska EM, Sunshine A, Mueller F, Elvers WB, Siegel C, Rubin A. Caffeine as an analgesic adjuvant.JAMA 1984;251:1711–1718.

    Google Scholar 

  • Lee SC, Shizukuda Y, Downey HF. Adenosine (ADO) increases oxygen utilization efficiency in canine myocardium (abstract).Circulation 1991;84(Suppl II):II94.

    Google Scholar 

  • Lewis T. Pain in muscular ischemia—its relation to anginal pain.Arch Intern Med 1932;49:713–727.

    Google Scholar 

  • Liang BT. Adenosine receptors and cardiovascular function.Trends Cardiovasc Med 1992;2:100–108.

    Google Scholar 

  • Libert F, Van Sande J, Lefort A, et al. Cloning and functional characterization of a human A1 adenosine receptor.Biochem Biophys Res Commun 1992;187:919–926

    Google Scholar 

  • Maenhaut C, Van Sande J, Libert F, et al. RDC8 codes for an adenosine A2 receptor with physiological constitutive activity.Biochem Biophys Res Commun 1990;173:1169–1178.

    Google Scholar 

  • Malliani A. The elusive link between transient myocardial ischemia and pain.Circulation 1986;73:201–204.

    Google Scholar 

  • Mannheimer C, Carlsson CA, Vedin A, Wilhelmson C. Transcutaneous electrical nerve stimulation in angina pectoris.Pain 1986;26:291–300.

    Google Scholar 

  • Marzilli M, Simonetti I, Levantesi D, et al. Effects of dilazep on coronary and systemic hemodynamics in humans.Am Heart J 1984;108:276–285.

    Google Scholar 

  • Marzilli M, Klassen GA, Marraccini P, Camici P, Trivella MG, L'Abbate A. Coronary effects of adenosine in conscious man.Eur Heart J 1989;10(Suppl F):78–81.

    Google Scholar 

  • Maseri A, Crea F, Kaski JC, Crake T. Mechanisms of angina pectoris in syndrome X: Editorial.J Am Coll Cardiol 1991b;17:499–506.

    Google Scholar 

  • Maseri A, Crea F, Kaski JC, Davies G. Mechanisms and significance of cardiac ischemic pain.Prog Cardiovasc Dis 1992;35:1–18.

    Google Scholar 

  • Masuda M, Demeulemeester A, Chang-Chun C, Flemeng W. Cardioprotective effects of nucleoside transport inhibition in ischemia-reperfused rabbit hearts. A role of endogenous adenosine (abstract).Circulation 1991;84(Suppl II):II306.

    Google Scholar 

  • Mathias MB, Schrader J. Adenine nucleotide release from isolated perfused guinea-pig hearts and extracellular formation of adenosine.Circ Res 1991;68:797–806.

    Google Scholar 

  • MacAlpin RN. Coronary arterial spasm.J Hist Med 1980;35:288–311.

    Google Scholar 

  • McQueen DS, Ribeiro JA. Effect of adenosine on carotid chemoreceptor activity in the cat.Br J Pharmacol 1981;74:129–136.

    Google Scholar 

  • Melzack R, Wall PD. Pain mechanisms: A new theory.Science 1965;150:971–979.

    Google Scholar 

  • Montano N, Lombardi F, Ruscone TG, Contini M, Guazzi M, Malliani A. The excitatory effect of adenosine on the discharge activity of the afferent cardiac sympathetic fibers.Cardiologia 1991;36:953–959.

    Google Scholar 

  • Moore RM. The stimulation of peripheral nerve elements subserving pain-sensibility by intra-arteral injections of neutral solutions.Am J Physiol 1934;110:191–197.

    Google Scholar 

  • Murphy DA, Armour JA. Human cardiac nerve stimulation.Ann Thorac Surg 1992;54:502–506.

    Google Scholar 

  • Nesto RW, Kowalchuk GJ. The ischemic cascade: Temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia.Am J Cardiol 1987;57:23C-30C.

    Google Scholar 

  • Newby AC. Adenosine and the concept of retaliatory metabolite.Trends Biochem Sci 1984;9:42–49.

    Google Scholar 

  • O'Keefe JH, Bateman TM, Silvestri R, Barnhart C. Safety and diagnostic accuracy of adenosine thallium-201 scintigraphy in patients unable to exercise and those with left bundle branch block.Am Heart J 1992;124:610–613.

    Google Scholar 

  • Olsson RA, Pearson ID. Cardiovascular purinoceptors.Physiol Rev 1990;70:761–845.

    Google Scholar 

  • Osswald H, Speilman WS, Knox FG. Mechanism of adenosine mediated decreases in glomerular filtrate in dogs.Circ Res 1978;43:465–469.

    Google Scholar 

  • Pappagallo M, Gaspardone A, Tomai F, Iamele M, Crea F, Gioffré PA. Analgesic effect of bamiphylline on pain induced by intradermal injection of adenosine.Pain 1993;53:199–204.

    Google Scholar 

  • Pernow B, Saltin B, Wahren J, Cronestrand R, Ekeström S. Leg blood flow and muscle metabolism in occlusive arterial disease of the leg before and after reconstructive surgery.Clin Sci Mol Med 1975;49:265–275.

    Google Scholar 

  • Pothier F, Couillard P, Forget J. ATP and the autonomy of the contractile vacuole inAmoeba proteus.J Exp Zool 1984;230:211–218.

    Google Scholar 

  • Rafflenbeul W, Bassenge E, Lichtlen P. Competition between endothelium-dependent and nitroglycerin-induced coronary vasodilation.Z Kardiol 1989;78(Suppl 2):45–47.

    Google Scholar 

  • Ramsdale DB, Bellamy CM. Angina and threatened acute myocardial infarction after cardiac transplantation.Am Heart J 1990;119:1195–1197.

    Google Scholar 

  • Ren H, Stiles GL. Genomic and cDNA cloning of the human A1 adenosine receptor (abstract).Circulation 1992;86(Suppl I):I304.

    Google Scholar 

  • Rubino A, Mantelli L, Amerini S, Ledda F. Adenosine modulation of non-adrenergic non-cholinergic neurotransmission in isolated guinea-pig atria.Naunyn-Schmiedebergs Arch Pharmacol 1990;342:520–522.

    Google Scholar 

  • Runold M, Prabhakar NR, Mitra J, Cherniack NS. Mechanism of respiratory augmentation by adenosine: Role of pulmonary afferents. In: Von Euler C, Katz-Salomon M, eds.Respiratory Psychophysiology. International Symposium Series, Vol 50. London: Macmillan 1988;175–182.

    Google Scholar 

  • Runold M, Cherniack, Prabhakar NR. Effect of adenosine on chemosensory activity of the cat aortic body.Respir Physiol 1990;80:299–306.

    Google Scholar 

  • Sahlin K, Areskog NH, Haller RG, Henriksson KG, Jorfeldt L, Lewis SF. Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease.J Appl Physiol 1990;69:1231–1235.

    Google Scholar 

  • Samuelsson VE, Wiklund NP, Gustafsson LE. Dual effects of adenosine and adenosine analogues on motor activity of the human fallopian tube.Acta Physiol Scand 1985;125:369–376.

    Google Scholar 

  • Sawynok J, Sweeny MI, White TD. Adenosine release may mediate spinal analgesia by morphine.Trends Pharmacol Sci 1989;10:186–189.

    Google Scholar 

  • Shapiro LM, Crake T, Poole-Wilsson PA. Is altered cardiac sensation responsible for chest pain in patients with normal coronary arteries?Br Med J 1988;296:170–171.

    Google Scholar 

  • Sheps DS, Adams, KF, Hinderliter A, et al. Endorphins are related to pain perception in coronary artery disease.Am J Cardiol 1987;59:523–527.

    Google Scholar 

  • Shryock JC, Travagli HC, Belardinelli L. Evaluation of N-0861, (+ −)-N6-endonorbornan-2-yl-9-methyladenine, as an A1 subtype-selective adenosine receptor antagonist in the guinea pig isolated heart.J Pharmacol Exp Ther 1992;260:1292–1299.

    Google Scholar 

  • Sollevi A, Lagerkranser M, Irestedt L, Gordon E, Lindquist C. Controlled hypotension with adenosine in cerebral aneurysm surgery.Anesthesiology 1984;61:400–405.

    Google Scholar 

  • Sosnowski M, Stevens CW, Yaksh TL. Assessment of the role of A1/A2 adenosine receptors mediating the purine antinociception, motor and autonomic function in the rat spinal cord.J Pharmacol Exp Ther 1989;250:915–922.

    Google Scholar 

  • Stark RP, McGinn AL, Wilson RF. Chest pain in cardiactransplant recipients. Evidence of sensory reinnervation after cardiac transplantation.N Engl J Med 1991;324:1791–1794.

    Google Scholar 

  • Strååt E, Henriksson P, Edlund A. Adenosine provokes myocardial ischaemia in patients with ischaemic heart disease without increasing cardiac work.J Intern Med 1991;230:319–323.

    Google Scholar 

  • Strååt E, Edlund A, Henriksson P. Improved working capacity in patients with ischaemic heart disease during a 10-day treatment with oral theophylline.J Intern Med 1992;232:53–58.

    Google Scholar 

  • Sylvén C, Beermann B, Jonzon B, Brandt R. Angina pectoris-like pain provoked by IV adenosine in healthy volunteers.Br Med J 1986;293:227–230.

    Google Scholar 

  • Sylvén C, Jonzon B, Brandt R, Beermann B. Adenosine provoked angina pectoris-like pain—time characteristics, influence of autonomic blockade and naloxone.Eur Heart J 1987;8:738–743.

    Google Scholar 

  • Sylvén C, Beermann B, Edlund A, Lewander R, Jonzon B, Mogensen L. Provocation of chest pain in patients with coronary insufficiency using the vasodilator adenosine.Eur Heart J 1988a:9(Suppl N):6–10.

    Google Scholar 

  • Sylvén C, Borg G, Brandt R, Beermann B, Jonzon B. Dose-effect relationship of adenosine provoked angina pectoris-like pain—a study of the psychophysical power function.Eur Heart J 1988b;9:86–91.

    Google Scholar 

  • Sylvén C, Kaijser L, Jonzon B, Fredholm BB. Effect of close intraarterial adenosine on forearm ischemic-like pain.Cardiovasc Res 1988c;22:674–678.

    Google Scholar 

  • Sylvén C, Edlund A, Jonzon B. Angina pectoris-like pain provoked by i.v. bolus of adenosine: Relationship to coronary sinus blood flow, heart rate and blood pressure in healthy volunteers.Eur Heart J 1989;10:48–54.

    Google Scholar 

  • Sylvén C, Beermann B, Kaijser L, Jonzon B. Nicotine enhances angina pectoris-like chest pain and atrioventricular blockade provoked by i.v. bolus of adenosine in healthy volunteers.J Cardiovasc Pharmacol 1990;16:962–965.

    Google Scholar 

  • Taylor P. Cholinergic agonists. In: Goodman AG, Goodman LS, Gilman A, eds.The Pharmacological Basis of Therapeutics, 6th ed. New York: Macmillan, 1980:91–99.

    Google Scholar 

  • Thames MD, Kinugawa T, Dibner-Dunlap ME. Reflex sympathoexcitation by cardiac sympathetic afferents during myocardial ischemia. Role of adenosine.Circulation 1993;87:1698–1704.

    Google Scholar 

  • Thorén P. Role of cardiac vagal c-fibers in cardiovascular control.Rev Physiol Biochem Pharmacol 1979;86:1–94.

    Google Scholar 

  • Turiel M, Galassi AR, Glazier JJ, et al. Pain threshold and tolerance in women with Syndrome X and women with stabile angina pectoris.Am J Cardiol 1987;60:503–508.

    Google Scholar 

  • Ushida Y, Murao S. Acid-induced excitation of afferent cardiac sympathetic nerve fibers.Am J Physiol 1975;228:33–37.

    Google Scholar 

  • Watson-Wright W, Boudreau G, Cardinal R, Armour JA. Beta 1- and beta 2-adrenoceptor subtypes in canine intrathoracic efferent sympathetic nervous system regulating the heart.Am J Physiol 1991;261:R1269-R1275.

    Google Scholar 

  • Webb SC, Poole-Wilson PA. Potassium exchange in the human heart during atrial pacing and myocardial ischaemia.Br Heart J 1986;55:554–559.

    Google Scholar 

  • Weiss J, Shine KI. Extracellular K+ activity changes in the canine myocardium after coronary occlusion and the influence of beta-blockade.Cardiovasc Res 1982;13:297–302.

    Google Scholar 

  • Virus RM, Djuricic-Nedelson M, Radulovacki M, Green RD. The effects of adenosine and 2'-deoxycoformycin on sleep and wakefulness in rats.Neuropharmacology 1983;22:1401–1404.

    Google Scholar 

  • Zhou QY, Li C, Olah ME, Johnson RA, Stiles GL, Civelli O. Molecular cloning and characterization of an adenosine receptor: The A3 adenosine receptor.Proc Natl Acad Sci USA 1992;89:7432–7436.

    Google Scholar 

  • Zimpfer M, Sit SP, Vatner SF. Effect of anesthesia on the canine carotid chemoreceptor reflex.Circ Res 1981;48:400–406.

    Google Scholar 

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  1. Department of Medicine, Huddinge University Hospital, S-141 86, Huddinge, Sweden

    Christer Sylvén MD, PhD (FACC, FESC)

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  1. Christer Sylvén MD, PhD
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Sylvén, C. Mechanisms of pain in angina pectoris—A critical review of the adenosine hypothesis. Cardiovasc Drug Ther 7, 745–759 (1993). https://doi.org/10.1007/BF00878926

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  • DOI: https://doi.org/10.1007/BF00878926

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