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. 1988 Feb;93(2):375–382. doi: 10.1111/j.1476-5381.1988.tb11444.x

The effects of the novel anti-anginal compound RS 43285 on myocardial conduction in the anaesthetized dog.

M C Allely 1, B J Alps 1
PMCID: PMC1853802  PMID: 3359110

Abstract

1. A pentobarbitone-anaesthetized canine model of myocardial conduction was developed to evaluate drug effects on intra-atrial (I-A), intra-ventricular (I-V) and atrioventricular (A-V) conduction parameters, both at rest and during electrical pacing of the right atrium or ventricle. Drug effects on the ability of the sino-atrial (SA) node to re-establish sinus rhythm on switching off electrical pacing were also considered. The effects of the novel anti-anginal compound RS 43285-193 ((+/-)-N-(2,6-dimethyl-phenyl)-4[2-hydroxy-3-(2-methoxyphenoxy)propyl] -1-piperazine acetamide dihydrochloride) were compared to those of the standard anti-anginal compounds nicardipine, nifedipine and verapamil. 2. In the dose range 15-7000 micrograms kg-1, RS 43285 had no significant effects on I-A, I-V or A-V conduction either at rest or during electrical pacing and did not affect the re-establishment of sinus rhythm. 3. Nicardipine had no effects on conduction parameters at resting heart rate. There were no effects on I-A or I-V conduction on electrical pacing but A-V conduction was increased at 200-500 micrograms kg-1 (with a 2:1 A-V conduction block in two out of six dogs); this was accompanied by a prolongation of the interval to reversion of sinus rhythm. 4. Nifedipine had no significant effects on I-A or I-V conduction but significantly prolonged A-V conduction at 1000 micrograms kg-1 and this dose also increased the interval to SA node recovery. 5. Verapamil did not effect I-A or I-V conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Bissett J. K., Kane J. J., De Soyza N., Murphy M. L. Electrophysiological significance of rapid atrial pacing as a test of atrioventricular conduction. Cardiovasc Res. 1975 Sep;9(5):593–599. doi: 10.1093/cvr/9.5.593. [DOI] [PubMed] [Google Scholar]
  2. Braun S., Terdiman R., Berenfeld D., Laniado S. Clinical and hemodynamic effects of combined propranolol and nifedipine therapy versus propranolol alone in patients with angina pectoris. Am Heart J. 1985 Mar;109(3 Pt 1):478–485. doi: 10.1016/0002-8703(85)90551-4. [DOI] [PubMed] [Google Scholar]
  3. Damato A. N., Lau S. H., Helfant R. H., Stein E., Berkowitz W. D., Cohen S. I. Study of atrioventricular conduction in man using electrode catheter recordings of His bundle activity. Circulation. 1969 Mar;39(3):287–296. doi: 10.1161/01.cir.39.3.287. [DOI] [PubMed] [Google Scholar]
  4. Dargie H., Cleland J., Findlay I., Murray G., McInnes G. Combination of verapamil and beta blockers in systemic hypertension. Am J Cardiol. 1986 Feb 26;57(7):80D–82D. doi: 10.1016/0002-9149(86)90812-x. [DOI] [PubMed] [Google Scholar]
  5. Denes P., Wu D., Dhingra R., Pietras R. J., Rosen K. M. The effects of cycle length on cardiac refractory periods in man. Circulation. 1974 Jan;49(1):32–41. doi: 10.1161/01.cir.49.1.32. [DOI] [PubMed] [Google Scholar]
  6. Elharrar V., Gaum W. E., Zipes D. P. Effect of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs. Am J Cardiol. 1977 Apr;39(4):544–549. doi: 10.1016/s0002-9149(77)80164-1. [DOI] [PubMed] [Google Scholar]
  7. Frishman W. H., Charlap S., Kimmel B., Goldberger J., Phillippides G., Klein N. Calcium-channel blockers for combined angina pectoris and systemic hypertension. Am J Cardiol. 1986 Feb 26;57(7):22D–29D. doi: 10.1016/0002-9149(86)90801-5. [DOI] [PubMed] [Google Scholar]
  8. Fujimoto T., Peter T., Hamamoto H., McCullen A. E., Mandel W. J. Effects of nifedipine on conduction delay during ventricular myocardial ischemia and reperfusion. Am Heart J. 1981 Jul;102(1):45–52. doi: 10.1016/0002-8703(81)90411-7. [DOI] [PubMed] [Google Scholar]
  9. Lazzara R., El-Sherif N., Hope R. R., Scherlag B. J. Ventricular arrhythmias and electrophysiological consequences of myocardial ischemia and infarction. Circ Res. 1978 Jun;42(6):740–749. doi: 10.1161/01.res.42.6.740. [DOI] [PubMed] [Google Scholar]
  10. Mangiardi L. M., Hariman R. J., McAllister R. G., Jr, Bhargava V., Surawicz B., Shabetai R. Electrophysiologic and hemodynamic effects of verapamin. Correlation with plasma drug concentrations. Circulation. 1978 Feb;57(2):366–372. doi: 10.1161/01.cir.57.2.366. [DOI] [PubMed] [Google Scholar]
  11. Millard R. W., Lathrop D. A., Grupp G., Ashraf M., Grupp I. L., Schwartz A. Differential cardiovascular effects of calcium channel blocking agents: potential mechanisms. Am J Cardiol. 1982 Feb 18;49(3):499–506. doi: 10.1016/s0002-9149(82)80002-7. [DOI] [PubMed] [Google Scholar]
  12. Rogel S., Hasin Y. Increased excitability of the heart induced by electrical stimulation in the absolute refractory period. Chest. 1971 Dec;60(6):578–582. doi: 10.1378/chest.60.6.578. [DOI] [PubMed] [Google Scholar]
  13. Rousseau M. F., Hanet C., Pardonge-Lavenne E., Van den Berghe G., Van Hoof F., Pouleur H. Changes in myocardial metabolism during therapy in patients with chronic stable angina: a comparison of long-term dosing with propranolol and nicardipine. Circulation. 1986 Jun;73(6):1270–1280. doi: 10.1161/01.cir.73.6.1270. [DOI] [PubMed] [Google Scholar]
  14. Rousseau M. F., Vincent M. F., Van Hoof F., Van den Berghe G., Charlier A. A., Pouleur H. Effects of nicardipine and nisoldipine on myocardial metabolism, coronary blood flow and oxygen supply in angina pectoris. Am J Cardiol. 1984 Dec 1;54(10):1189–1194. doi: 10.1016/s0002-9149(84)80065-x. [DOI] [PubMed] [Google Scholar]
  15. Scherlag B. J., Kosowsky B. D., Damato A. N. A technique for ventricular pacing from the His bundle of the intact heart. J Appl Physiol. 1967 Mar;22(3):584–587. doi: 10.1152/jappl.1967.22.3.584. [DOI] [PubMed] [Google Scholar]
  16. Singh B. N., Ellrodt G., Peter C. T. Verapamil: a review of its pharmacological properties and therapeutic use. Drugs. 1978 Mar;15(3):169–197. doi: 10.2165/00003495-197815030-00001. [DOI] [PubMed] [Google Scholar]
  17. Winniford M. D., Markham R. V., Jr, Firth B. G., Nicod P., Hillis L. D. Hemodynamic and electrophysiologic effects of verapamil and nifedipine in patients on propranolol. Am J Cardiol. 1982 Oct;50(4):704–710. doi: 10.1016/0002-9149(82)91222-x. [DOI] [PubMed] [Google Scholar]

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