Abstract
Adenosine levels in oxygen-deprived myocardium can rise to 10- 100 microM concentrations known to cause atrioventricular (AV) conduction delay and block. We reported that the AV conduction delay and block caused by hypoxia is markedly attenuated by 10 microM aminophylline, and adenosine competitive antagonist. THe purpose of the present study was to investigate adenosine's role in ischemic AV conduction disturbances. Dogs were anesthetized and instrumented for His bundle and surface electrogram recordings. The total AV conduction time was subdivided in to atrial-His bundle (AH) and His bundle-ventricle intervals. The atrioventricular node artery (AVNA) was cannulated for selective injection of drugs in the AV node region. Adenosine (10 to 100 microgram), as a 2-ml bolus injection, rapidly produced a dose-dependent, transient increase in the AH interval; a 1,000-microgram dose caused second degree AV block. The duration of the increase in AH interval was also dose-dependent. Dipyridamole, and inhibitor of nucleoside transport, potentiated the negative dromotropic effects of adenosine, whereas aminophylline attenuated them. In some dogs, after cannulation of the AVNA, first and second degree AV block occurred spontaneously or were induced by rapid atrial pacing. Injection of the aminophylline (5 mg/kg, i.e.) or theophylline (100-1,000 microgram) into the AVNA rapidly reversed the AV blocks. Upon washout of the drugs the AV blocks recurred. We conclude that endogenously released adenosine may account for a major fraction of the AV conduction delay and block associated with impaired blood supply to the AV node, and the theophylline and aminophylline reverse the AV conduction defect by antagonizing the effects of adenosine.
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Selected References
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- ALANIS J., LOPEZ E., MANDOKI J. J., PILAR G. Propagation of impulses through the atrioventricular node. Am J Physiol. 1959 Dec;197:1171–1174. doi: 10.1152/ajplegacy.1959.197.6.1171. [DOI] [PubMed] [Google Scholar]
- Adgey A. A., Geddes J. S., Mulholland H. C., Keegan D. A., Pantridge J. F. Incidence, significance, and management of early bradyarrhythmia complicating acute myocardial infarction. Lancet. 1968 Nov 23;2(7578):1097–1101. doi: 10.1016/s0140-6736(68)91577-8. [DOI] [PubMed] [Google Scholar]
- Akiyama T., Fozzard H. A. Ca and Na selectivity of the active membrane of rabbit AV nodal cells. Am J Physiol. 1979 Jan;236(1):C1–C8. doi: 10.1152/ajpcell.1979.236.1.C1. [DOI] [PubMed] [Google Scholar]
- BAGDONAS A. A., STUCKEY J. H., PIERA J., AMER N. S., HOFFMAN B. F. Effects of ischemia and hypoxia on the specialized conducting system of the canine heart. Am Heart J. 1961 Feb;61:206–218. doi: 10.1016/0002-8703(61)90577-4. [DOI] [PubMed] [Google Scholar]
- BUTCHER R. W., SUTHERLAND E. W. Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine. J Biol Chem. 1962 Apr;237:1244–1250. [PubMed] [Google Scholar]
- Beavo J. A., Rogers N. L., Crofford O. B., Hardman J. G., Sutherland E. W., Newman E. V. Effects of xanthine derivatives on lipolysis and on adenosine 3',5'-monophosphate phosphodiesterase activity. Mol Pharmacol. 1970 Nov;6(6):597–603. [PubMed] [Google Scholar]
- Belardinelli L., Belloni F. L., Rubio R., Berne R. M. Atrioventricular conduction disturbances during hypoxia. Possible role of adenosine in rabbit and guinea pig heart. Circ Res. 1980 Nov;47(5):684–691. doi: 10.1161/01.res.47.5.684. [DOI] [PubMed] [Google Scholar]
- Belardinelli L., Rubio R., Berne R. M. Blockade of Ca2+ dependent rat atrial slow action potentials by adenosine and lanthanum. Pflugers Arch. 1979 May 15;380(1):19–27. doi: 10.1007/BF00582607. [DOI] [PubMed] [Google Scholar]
- Benítez D., Mascher D., Alanis J. The electrical activity of the bundle of His. The fast and slow inward currents. Pflugers Arch. 1973 Dec 7;345(1):61–72. doi: 10.1007/BF00587062. [DOI] [PubMed] [Google Scholar]
- Degenring F. H., Curnish R. R., Rubio R., Berne R. M. Effect of dipyridamole on myocardial adenosine metabolism and coronary flow in hypoxia and reactive hyperemia in the isolated perfused guinea pig heart. J Mol Cell Cardiol. 1976 Nov;8(11):877–888. doi: 10.1016/0022-2828(76)90070-5. [DOI] [PubMed] [Google Scholar]
- Drury A. N., Szent-Györgyi A. The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. J Physiol. 1929 Nov 25;68(3):213–237. doi: 10.1113/jphysiol.1929.sp002608. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fam W. M., McGregor M. Effect of nitroglycerin and dipyridamole on regional coronary resistance. Circ Res. 1968 May;22(5):649–659. doi: 10.1161/01.res.22.5.649. [DOI] [PubMed] [Google Scholar]
- Fox A. C., Reed G. E., Glassman E., Kaltman A. J., Silk B. B. Release of adenosine from human hearts during angina induced by rapid atrial pacing. J Clin Invest. 1974 May;53(5):1447–1457. doi: 10.1172/JCI107693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillespie J. H. The biological significance of the linkages in adenosine triphosphoric acid. J Physiol. 1934 Feb 28;80(4):345–359. doi: 10.1113/jphysiol.1934.sp003095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartzell H. C. Adenosine receptors in frog sinus venosus: slow inhibitory potentials produced by adenine compounds and acetylcholine. J Physiol. 1979 Aug;293:23–49. doi: 10.1113/jphysiol.1979.sp012877. [DOI] [PMC free article] [PubMed] [Google Scholar]
- James T. N., Bear E. S., Frink R. J., Lang K. F., Tomlinson J. C. Selective stimulation, suppression, or blockade of the atrioventricular node and His bundle. J Lab Clin Med. 1970 Aug;76(2):240–256. [PubMed] [Google Scholar]
- Kolassa N., Pfleger K., Rummel W. Specificity of adenosine uptake into the heart and inhibition by dipyridamole. Eur J Pharmacol. 1970 Mar;9(3):265–268. doi: 10.1016/0014-2999(70)90221-9. [DOI] [PubMed] [Google Scholar]
- LUMB G., SHACKLETT R. S., DAWKINS W. A. The cardiac conduction tissue and its blood supply in the dog. Am J Pathol. 1959 May-Jun;35(3):467–487. [PMC free article] [PubMed] [Google Scholar]
- Miller W. L., Belardinelli L., Bacchus A., Foley D. H., Rubio R., Berne R. M. Canine myocardial adenosine and lactate production, oxygen consumption, and coronary blood flow during stellate ganglia stimulation. Circ Res. 1979 Dec;45(6):708–718. doi: 10.1161/01.res.45.6.708. [DOI] [PubMed] [Google Scholar]
- Motomura S., Iijima T., Taira N., Hashimoto K. Effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular junctional area of the dog heart. Circ Res. 1975 Aug;37(2):146–155. doi: 10.1161/01.res.37.2.146. [DOI] [PubMed] [Google Scholar]
- Nadeau R. A., Amir-Jahed A. K. Selective perfusion of the AV node of the dog by cannulation of the posterior septal artery. Rev Can Biol. 1965 Dec;24(4):291–297. [PubMed] [Google Scholar]
- Ogilvie R. I., Fernandez P. G., Winsberg F. Cardiovascular response to increasing theophylline concentrations. Eur J Clin Pharmacol. 1977 Dec 28;12(6):409–414. doi: 10.1007/BF00561059. [DOI] [PubMed] [Google Scholar]
- Rubio R., Wiedmeier V. T., Berne R. M. Relationship between coronary flow and adenosine production and release. J Mol Cell Cardiol. 1974 Dec;6(6):561–566. doi: 10.1016/0022-2828(74)90036-4. [DOI] [PubMed] [Google Scholar]
- Schrader J., Baumann G., Gerlach E. Adenosine as inhibitor of myocardial effects of catecholamines. Pflugers Arch. 1977 Nov 25;372(1):29–35. doi: 10.1007/BF00582203. [DOI] [PubMed] [Google Scholar]
- Schrader J., Rubio R., Berne R. M. Inhibition of slow action potentials of guinea pig atrial muscle by adenosine: a possible effect on Ca2+ influx. J Mol Cell Cardiol. 1975 Jun;7(6):427–433. doi: 10.1016/0022-2828(75)90048-6. [DOI] [PubMed] [Google Scholar]
- Senges J., Mizutani T., Pelzer D., Brachmann J., Sonnhof U., Kübler W. Effect of hypoxia on the sinoatrial node, atrium, and atrioventricular node in the rabbit heart. Circ Res. 1979 Jun;44(6):856–863. doi: 10.1161/01.res.44.6.856. [DOI] [PubMed] [Google Scholar]
- Stafford A. Potentiation of adenosine and the adenine nucleotides by dipyridamole. Br J Pharmacol Chemother. 1966 Nov;28(2):218–227. doi: 10.1111/j.1476-5381.1966.tb01888.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas R. A., Rubio R., Berne R. M. Comparison of the adenine nucleotide metabolism of dog atrial and ventricular myocardium. J Mol Cell Cardiol. 1975 Feb;7(2):115–123. doi: 10.1016/0022-2828(75)90013-9. [DOI] [PubMed] [Google Scholar]
- Urthaler F., James T. N. A comparison of His bundle electrograms recorded from the aortic root and from a plaque sutured near the His bundle. J Lab Clin Med. 1975 May;85(5):711–722. [PubMed] [Google Scholar]
- Urthaler F., James T. N. Effects of adenosine and ATP on AV conduction and on AV junctional rhythm. J Lab Clin Med. 1972 Jan;79(1):96–105. [PubMed] [Google Scholar]
- Urthaler F., James T. N. Experimental studies on the pathogenesis of asystole after verapamil in the dog. Am J Cardiol. 1979 Oct;44(4):651–656. doi: 10.1016/0002-9149(79)90283-2. [DOI] [PubMed] [Google Scholar]
- Westfall D. P., Fleming W. W. Sensitivity changes in the dog heart to norepinephrine, calcium and aminophyline resulting from pretreatment with reserpine. J Pharmacol Exp Ther. 1968 Jan;159(1):98–106. [PubMed] [Google Scholar]
- Wit A. L., Cranefield P. F. Effect of verapamil on the sinoatrial and atrioventricular nodes of the rabbit and the mechanism by which it arrests reentrant atrioventricular nodal tachycardia. Circ Res. 1974 Sep;35(3):413–425. doi: 10.1161/01.res.35.3.413. [DOI] [PubMed] [Google Scholar]
- Zipes D. P., Fischer J. C. Effects of agents which inhibit the slow channel on sinus node automaticity and atrioventricular conduction in the dog. Circ Res. 1974 Feb;34(2):184–192. doi: 10.1161/01.res.34.2.184. [DOI] [PubMed] [Google Scholar]
- Zumino A. Z., Parisii I. M., De Ceretti E. R. Effect of ischemia and low-sodium medium on atrioventricular conduction. Am J Physiol. 1970 May;218(5):1489–1494. doi: 10.1152/ajplegacy.1970.218.5.1489. [DOI] [PubMed] [Google Scholar]