Abstract
1. To clarify whether the bradycardic agent UL-FS 49 exhibits a positive inotropic effect even in the absence of improvement in regional myocardial function of an underperfused myocardial area, this study was undertaken in dogs with unimpaired coronary flow. 2. We also investigated the haemodynamic and functional effects of the negative chronotropic and inotropic beta-adrenoceptor blocker propranolol. 3. UL-FS 49 did not depress total or regional myocardial performance. Moreover, an increase in positive left ventricular dp/dt max at rest suggests a positive inotropic effect of UL-FS 49. 4. Propranolol, in contrast to UL-FS 49, led to a marked reduction in positive dp/dt max, stroke volume and systolic wall thickening at rest and during exercise. Additionally, propranolol decreased the exercise values of cardiac output, left ventricular work and left ventricular power to a far greater extent than UL-FS 49. 5. In contrast to propranolol, the selective bradycardic agent UL-FS 49 did not decrease total or regional ventricular performance and caused less reduction in cardiodynamic parameters during exercise. 6. These results suggest that patients with moderate coronary insufficiency or patients with coronary vessel disease and mild left ventricular failure may attain a higher exercise limit under selective bradycardia with UL-FS 49 in comparison to that possible with a beta-adrenoceptor antagonist, such as propranolol.
Full text
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akaishi M., Schneider R. M., Mercier R. J., Naccarella F. F., Agarwal J. B., Helfant R. H., Weintraub W. S. Relation between left ventricular global and regional function and extent of myocardial ischemia in the canine heart. J Am Coll Cardiol. 1985 Jul;6(1):104–112. doi: 10.1016/s0735-1097(85)80260-6. [DOI] [PubMed] [Google Scholar]
- BERGLUND E., BORST H. G., DUFF F., SCHREINER G. L. Effect of heart rate on cardiac work, myocardial oxygen consumption and coronary blood flow in the dog. Acta Physiol Scand. 1958 Feb 4;42(2):185–198. doi: 10.1111/j.1748-1716.1958.tb01551.x. [DOI] [PubMed] [Google Scholar]
- Boerth R. C., Covell J. W., Pool P. E., Ross J., Jr Increased myocardial oxygen consumption and contractile state associated with increased heart rate in dogs. Circ Res. 1969 May;24(5):725–734. doi: 10.1161/01.res.24.5.725. [DOI] [PubMed] [Google Scholar]
- Boudoulas H., Lewis R. P., Rittgers S. E., Leier C. V., Vasko J. S. Increased diastolic time: a possible important factor in the benefical effect of propranolol in patients with coronary artery disease. J Cardiovasc Pharmacol. 1979 Sep-Oct;1(5):503–513. [PubMed] [Google Scholar]
- Epstein S., Robinson B. F., Kahler R. L., Braunwald E. Effects of beta-adrenergic blockade on the cardiac response to maximal and submaximal exercise in man. J Clin Invest. 1965 Nov;44(11):1745–1753. doi: 10.1172/JCI105282. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallagher K. P., Matsuzaki M., Osakada G., Kemper W. S., Ross J., Jr Effect of exercise on the relationship between myocardial blood flow and systolic wall thickening in dogs with acute coronary stenosis. Circ Res. 1983 Jun;52(6):716–729. doi: 10.1161/01.res.52.6.716. [DOI] [PubMed] [Google Scholar]
- Guth B. D., Heusch G., Seitelberger R., Ross J., Jr Elimination of exercise-induced regional myocardial dysfunction by a bradycardiac agent in dogs with chronic coronary stenosis. Circulation. 1987 Mar;75(3):661–669. doi: 10.1161/01.cir.75.3.661. [DOI] [PubMed] [Google Scholar]
- Higgins C. B., Vatner S. F., Franklin D., Braunwald E. Extent of regulation of the heart's contractile state in the conscious dog by alteration in the frequency of contraction. J Clin Invest. 1973 May;52(5):1187–1194. doi: 10.1172/JCI107285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ho S. W., McComish M. J., Taylor R. R. Effect of beta-adrenergic blockade on the results of exercise testing related to the extent of coronary artery disease. Am J Cardiol. 1985 Feb 1;55(4):258–262. doi: 10.1016/0002-9149(85)90356-x. [DOI] [PubMed] [Google Scholar]
- Kobinger W., Lillie C. Cardiovascular characterization of UL-FS 49, 1,3,4,5-tetrahydro-7,8-dimethoxy-3-[3-][2-(3,4-dimethoxyphenyl)ethyl] methylimino]propyl]-2H-3-benzazepin-2-on hydrochloride, a new "specific bradycardic agent". Eur J Pharmacol. 1984 Sep 3;104(1-2):9–18. doi: 10.1016/0014-2999(84)90363-7. [DOI] [PubMed] [Google Scholar]
- Kobinger W., Lillie C., Pichler L. Cardiovascular actions of N-allyl-clonidine (ST 567), a substance with specific bradycardic action. Eur J Pharmacol. 1979 Sep 15;58(2):141–150. doi: 10.1016/0014-2999(79)90005-0. [DOI] [PubMed] [Google Scholar]
- Krumpl G., Mayer N., Schneider W., Raberger G. Effects of alinidine on exercise-induced regional contractile dysfunction in dogs. Eur J Pharmacol. 1986 Oct 14;130(1-2):37–46. doi: 10.1016/0014-2999(86)90181-0. [DOI] [PubMed] [Google Scholar]
- Krumpl G., Schneider W., Raberger G. Can exercise-induced regional contractile dysfunction be prevented by selective bradycardic agents? Naunyn Schmiedebergs Arch Pharmacol. 1986 Dec;334(4):540–543. doi: 10.1007/BF00569399. [DOI] [PubMed] [Google Scholar]
- LAURENT D., BOLENE-WILLIAMS C., WILLIAMS F. L., KATZ L. N. Effects of heart rate on coronary flow and cardiac oxygen consumption. Am J Physiol. 1956 May;185(2):355–364. doi: 10.1152/ajplegacy.1956.185.2.355. [DOI] [PubMed] [Google Scholar]
- Lillie C., Kobinger W. Investigations into the bradycardic effects of UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl)ethyl] methylimino]propyl]-2H-3-benzazepin-2-on-hydrochloride) in isolated guinea pig atria. J Cardiovasc Pharmacol. 1986 Jul-Aug;8(4):791–797. [PubMed] [Google Scholar]
- Mahler F., Yoran C., Ross J., Jr Intropic effect of tachycardia and poststimulation potentiation in the conscious dog. Am J Physiol. 1974 Sep;227(3):569–575. doi: 10.1152/ajplegacy.1974.227.3.569. [DOI] [PubMed] [Google Scholar]
- Mayer N., Krumpl G., Schneider W., Raberger G. Propranolol ameliorates exercise-induced regional myocardial dysfunction in dogs. Clin Exp Pharmacol Physiol. 1986 Nov-Dec;13(11-12):791–799. doi: 10.1111/j.1440-1681.1986.tb02383.x. [DOI] [PubMed] [Google Scholar]
- Millar J. S., Williams E. M. Pacemaker selectivity: influence on rabbit atria of ionic environment and of alinidine, a possible anion antagonist. Cardiovasc Res. 1981 Jun;15(6):335–350. doi: 10.1093/cvr/15.6.335. [DOI] [PubMed] [Google Scholar]
- Quinones M. A., Gaasch W. H., Alexander J. K. Influence of acute changes in preload, afterload, contractile state and heart rate on ejection and isovolumic indices of myocardial contractility in man. Circulation. 1976 Feb;53(2):293–302. doi: 10.1161/01.cir.53.2.293. [DOI] [PubMed] [Google Scholar]
- Raberger G., Krumpl G., Mayer N. A model of transient myocardial dysfunction in conscious dogs. Regional shortening in the presence of impaired coronary flow reserve and treadmill exercise. J Pharmacol Methods. 1986 Aug;16(1):23–37. doi: 10.1016/0160-5402(86)90026-4. [DOI] [PubMed] [Google Scholar]
- Raberger G., Krumpl G., Schneider W. Effects of the bradycardic agent UL-FS 49 on exercise-induced regional contractile dysfunction in dogs. Int J Cardiol. 1987 Mar;14(3):343–354. doi: 10.1016/0167-5273(87)90205-1. [DOI] [PubMed] [Google Scholar]
- Sasayama S., Gallagher K. P., Kemper W. S., Franklin D., Ross J., Jr Regional left ventricular wall thickness early and late after coronary occlusion in the conscious dog. Am J Physiol. 1981 Feb;240(2):H293–H299. doi: 10.1152/ajpheart.1981.240.2.H293. [DOI] [PubMed] [Google Scholar]
- Sklar J., Johnston G. D., Overlie P., Gerber J. G., Brammell H. L., Gal J., Nies A. S. The effects of a cardioselective (metoprolol) and a nonselective (propranolol) beta-adrenergic blocker on the response to dynamic exercise in normal men. Circulation. 1982 May;65(5):894–899. doi: 10.1161/01.cir.65.5.894. [DOI] [PubMed] [Google Scholar]
- Sonnenblick E. H., Ross J., Jr, Braunwald E. Oxygen consumption of the heart. Newer concepts of its multifactoral determination. Am J Cardiol. 1968 Sep;22(3):328–336. doi: 10.1016/0002-9149(68)90117-3. [DOI] [PubMed] [Google Scholar]
- Theroux P., Franklin D., Ross J., Jr, Kemper W. S. Regional myocardial function during acute coronary artery occlusion and its modification by pharmacologic agents in the dog. Circ Res. 1974 Dec;35(6):896–908. doi: 10.1161/01.res.35.6.896. [DOI] [PubMed] [Google Scholar]
- Theroux P., Ross J., Jr, Franklin D., Kemper W. S., Sasyama S. Regional Myocardial function in the conscious dog during acute coronary occlusion and responses to morphine, propranolol, nitroglycerin, and lidocaine. Circulation. 1976 Feb;53(2):302–314. doi: 10.1161/01.cir.53.2.302. [DOI] [PubMed] [Google Scholar]
- Wilmore J. H., Freund B. J., Joyner M. J., Hetrick G. A., Hartzell A. A., Strother R. T., Ewy G. A., Faris W. E. Acute response to submaximal and maximal exercise consequent to beta-adrenergic blockade: implications for the prescription of exercise. Am J Cardiol. 1985 Apr 26;55(10):135D–141D. doi: 10.1016/0002-9149(85)91070-7. [DOI] [PubMed] [Google Scholar]