Abstract
The relation between myocardial tissue cyclic AMP (cAMP) and the vulnerability to ventricular fibrillation was assessed in the isolated perfused rat heart by measurement of ventricular fibrillation threshold (VFT) and vulnerable period duration (VP). Exogenous dibutyryl cyclic AMP (DBcAMP) reduced VFT and increased VP by a concentration-related action whereas exogenous cAMP did not. Theophylline (1.0 mmol/liter) increased the tissue content of cAMP by 58% (P < 0.001) and caused a leftward shift in the concentration-response curve to DBcAMP. An effect of cAMP on VFT and VP could be shown in the presence of phosphodiesterase inhibition by theophylline. β-1-Adrenergic receptor blockade with atenolol did not alter the concentration-response curve for VFT when DBcAMP was administered. Epinephrine (100 nmol/liter to 1 μmol/liter) also increased vulnerability to VF; this effect was accompanied by a concentration-related increase in tissue cAMP, but inconsistent changes in tissue ATP, phosphocreatine and potassium. The concentration-response curve of VFT to epinephrine was shifted leftward by theophylline and rightward by atenolol.
The increases in vulnerability to fibrillation in the isolated perfused rat heart, in response to DBcAMP, theophylline or epinephrine, could be related more closely to changes of tissue cAMP than to effects on tissue high energy phosphates or potassium. The effect of epinephrine and theophylline on vulnerability to ventricular fibrillation is mediated via alterations in the intracellular level of cAMP in the isolated perfused rat heart.
Full text
PDF









Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Axelrod P. J., Verrier R. L., Lown B. Vulnerability to ventricular fibrillation during acute coronary arterial occlusion and release. Am J Cardiol. 1975 Nov;36(6):776–782. doi: 10.1016/0002-9149(75)90459-2. [DOI] [PubMed] [Google Scholar]
- Borer J. S., Harrison L. A., Kent K. M., Levy R., Goldstein R. E., Epstein S. E. Beneficial effect of lidocaine on ventricular electrical stability and spontaneous ventricular fibrillation during experimental myocardial infarction. Am J Cardiol. 1976 May;37(6):860–863. doi: 10.1016/0002-9149(76)90110-7. [DOI] [PubMed] [Google Scholar]
- Brown B. L., Albano J. D., Ekins R. P., Sgherzi A. M. A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate. Biochem J. 1971 Feb;121(3):561–562. doi: 10.1042/bj1210561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burgess M. J., Abildskov J. A., Millar K., Geddes J. S., Green L. S. Time course of vulnerability to fibrillation after experimental coronary occlusion. Am J Cardiol. 1971 Jun;27(6):617–621. doi: 10.1016/0002-9149(71)90225-6. [DOI] [PubMed] [Google Scholar]
- Ceremuzyński L., Staszewska-Barczak J., Herbaczynska-Cedro K. Cardiac rhythm disturbances and the release of catecholamines after acute coronary occlusion in dogs. Cardiovasc Res. 1969 Apr;3(2):190–197. doi: 10.1093/cvr/3.2.190. [DOI] [PubMed] [Google Scholar]
- Cheung W. Y., Williamson J. R. Kinetics of cyclic adenosine monophosphate changes in rat heart following epinephrine administration. Nature. 1965 Aug 28;207(5000):979–981. doi: 10.1038/207979b0. [DOI] [PubMed] [Google Scholar]
- Corbalan R., Verrier R. L., Lown B. Differing mechanisms for ventricular vulnerability during coronary artery occlusion and release. Am Heart J. 1976 Aug;92(2):223–230. doi: 10.1016/s0002-8703(76)80258-x. [DOI] [PubMed] [Google Scholar]
- Darby S., Cruickshank J. C., Bennett M. A., Pentecost B. L. Trial of combined intramuscular and intravenous lignocaine in prophylaxis of ventricular tachyarrhythmias. Lancet. 1972 Apr 15;1(7755):817–819. doi: 10.1016/s0140-6736(72)90801-x. [DOI] [PubMed] [Google Scholar]
- Fox K. M., Chopra M. P., Portal R. W., Aber C. P. Long-term beta blockade: possible protection from myocardial infarction. Br Med J. 1975 Jan 18;1(5950):117–119. doi: 10.1136/bmj.1.5950.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Han J. Ventricular vulnerability during acute coronary occlusion. Am J Cardiol. 1969 Dec;24(6):857–864. doi: 10.1016/0002-9149(69)90476-7. [DOI] [PubMed] [Google Scholar]
- Jewitt D. E., Reid D., Thomas M., Mercer C. J., Valori C., Shillingford J. P. Free noradrenaline and adrenaline excretion in relation to the development of cardiac arrhythmias and heart-failure in patients with acute myocardial infarction. Lancet. 1969 Mar 29;1(7596):635–641. doi: 10.1016/s0140-6736(69)92009-1. [DOI] [PubMed] [Google Scholar]
- Khan M. I., Hamilton J. T., Manning G. W. Protective effect of beta adrenoceptor blockade in experimental coronary occlusion in conscious dogs. Am J Cardiol. 1972 Dec;30(8):832–837. doi: 10.1016/0002-9149(72)90007-0. [DOI] [PubMed] [Google Scholar]
- Lubbe W. F., Bricknell O. L., Marzagao C. Ventricular fibrillation threshold and vulnerable period in the isolated perfused rat heart. Cardiovasc Res. 1975 Sep;9(5):613–620. doi: 10.1093/cvr/9.5.613. [DOI] [PubMed] [Google Scholar]
- Lubbe W. F., Bricknell O. L., Podzuweit H. O. Cyclic AMP as a determinant of vulnerability to ventricular fibrillation in the isolated rat heart. Cardiovasc Res. 1976 Nov;10(6):697–702. doi: 10.1093/cvr/10.6.697. [DOI] [PubMed] [Google Scholar]
- Meesmann W., Gülker H., Krämer B., Stephan K. Time course of changes in ventricular fibrillation threshold in myocardial infarction: characteristics of acute and slow occlusion with respect to the collateral vessels of the heart. Cardiovasc Res. 1976 Jul;10(4):466–473. doi: 10.1093/cvr/10.4.466. [DOI] [PubMed] [Google Scholar]
- Opie L. H., Mansford K. R., Owen P. Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats. Biochem J. 1971 Sep;124(3):475–490. doi: 10.1042/bj1240475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- POSTERNAK T., SUTHERLAND E. W., HENION W. F. Derivatives of cyclic 3',5'-adenosine monophosphate. Biochim Biophys Acta. 1962 Dec 17;65:558–560. doi: 10.1016/0006-3002(62)90475-4. [DOI] [PubMed] [Google Scholar]
- Pentecost B. L., Austen W. G. Beta-adrenergic blockade in experimental myocardial infarction. Am Heart J. 1966 Dec;72(6):790–796. doi: 10.1016/0002-8703(66)90162-1. [DOI] [PubMed] [Google Scholar]
- Podzuweit T., Lubbe W. F., Opie L. H. Cyclic adenosine monophosphate, ventricular fibrillation, and antiarrhythmic drugs. Lancet. 1976 Feb 14;1(7955):341–342. doi: 10.1016/s0140-6736(76)90090-8. [DOI] [PubMed] [Google Scholar]
- Reuter H. Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle. J Physiol. 1974 Oct;242(2):429–451. doi: 10.1113/jphysiol.1974.sp010716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schaal S. F., Wallace A. G., Sealy W. C. Protective influence of cardiac denervation against arrhythmias of myocardial infarction. Cardiovasc Res. 1969 Jul;3(3):241–244. doi: 10.1093/cvr/3.3.241. [DOI] [PubMed] [Google Scholar]
- Schaffer W. A., Cobb L. A. Recurrent ventricular fibrillation and modes of death in survivors of out-of-hospital ventricular fibrillation. N Engl J Med. 1975 Aug 7;293(6):259–262. doi: 10.1056/NEJM197508072930601. [DOI] [PubMed] [Google Scholar]
- Schneider J. A., Sperelakis N. Slow Ca2+ and Na+ responses induced by isoproterenol and methylxanthines in isolated perfused guinea pig hearts exposed to elevated K+. J Mol Cell Cardiol. 1975 Apr;7(4):249–273. doi: 10.1016/0022-2828(75)90084-x. [DOI] [PubMed] [Google Scholar]
- Stewart I. M. Compared incidence of first myocardial infarction in hypertensive patients under treatment containing propranolol or excluding beta-receptor blockade. Clin Sci Mol Med Suppl. 1976 Dec;3:509s–511s. doi: 10.1042/cs051509s. [DOI] [PubMed] [Google Scholar]
- Sutherland E. W., Robison G. A. The role of cyclic-3',5'-AMP in responses to catecholamines and other hormones. Pharmacol Rev. 1966 Mar;18(1):145–161. [PubMed] [Google Scholar]
- Tsien R. W. Adrenaline-like effects of intracellular iontophoresis of cyclic AMP in cardiac Purkinje fibres. Nat New Biol. 1973 Sep 26;245(143):120–122. doi: 10.1038/newbio245120a0. [DOI] [PubMed] [Google Scholar]
- WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]
- Wilhelmsson C., Vedin J. A., Wilhelmsen L., Tibblin G., Werkö L. Reduction of sudden deaths after myocardial infarction by treatment with alprenolol. Preliminary results. Lancet. 1974 Nov 16;2(7890):1157–1160. doi: 10.1016/s0140-6736(74)90807-1. [DOI] [PubMed] [Google Scholar]
- Wollenberger A., Krause E. G., Heier G. Stimulation of 3',5'-cyclic AMP formation in dog myocardium following arrest of blood flow. Biochem Biophys Res Commun. 1969 Aug 15;36(4):664–670. doi: 10.1016/0006-291x(69)90357-x. [DOI] [PubMed] [Google Scholar]
