PMID- 7714763
OWN - NLM
STAT- MEDLINE
DCOM- 19950517
LR  - 20161123
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 273
IP  - 1
DP  - 1995 Apr
TI  - Cardiac electrophysiologic and antiarrhythmic actions of tedisamil.
PG  - 168-75
AB  - The Class III electrophysiologic and antiarrhythmic actions of the bradycardic 
      agent tedisamil were assessed in vitro and in vivo. In ferret isolated right 
      ventricular papillary muscles, tedisamil increased effective refractory period 
      (ERP) in a concentration-dependent manner, with a 25% ERP increase achieved with 
      3.0 microM tedisamil, and a 133.4% +/- 28.8% increase in ERP achieved at the high 
      100 microM concentration tested. In anesthetized dogs, the cumulative i.v. 
      administration of tedisamil significantly increased ventricular relative 
      refractory period (VRRP) and ventricular effective refractory period (VERP) as 
      well as electrocardiographic QTc intervals (100-1000 micrograms/kg i.v.). A 
      20msec increase in VRRP was achieved with 45.0 micrograms/kg i.v. tedisamil, and 
      a 56.1 +/- 9.8 msec (40.1% +/- 8.1%) increase in VRRP was achieved at the highest 
      dose tested (1000 micrograms/kg i.v.). In the same dosage range in anesthetized 
      dogs, tedisamil produced significant hemodynamic effects, including reduction in 
      HR (100-1000 micrograms/kg i.v.) and elevations in mean arterial pressure (1000 
      micrograms/kg i.v.), left ventricular developed pressure (1000 micrograms/kg 
      i.v.) and the maximum rate of LV pressure development (100-1000 micrograms/kg 
      i.v.). In anesthetized dogs studied chronically (8.2 +/- 0.6 days) after anterior 
      myocardial infarction, tedisamil suppressed programmed stimulation-induced 
      ventricular tachyarrhythmias (8/10, 80% suppression at 100-1000 micrograms/kg 
      i.v.) and reduced the incidence of lethal ischemic arrhythmias developing in 
      response to acute posterolateral myocardial ischemia (arrhythmic mortality 5/10, 
      50% tedisamil vs. 34/40, 85% vehicle control cohort; P = .027). The latter 
      findings suggest that tedisamil might be useful in the prevention of malignant 
      ventricular arrhythmias in the setting of myocardial ischemic injury.(ABSTRACT 
      TRUNCATED AT 250 WORDS)
FAU - Wallace, A A
AU  - Wallace AA
AD  - Department of Pharmacology, Merck Research Laboratories, West Point, 
      Pennsylvania, USA.
FAU - Stupienski, R F 3rd
AU  - Stupienski RF 3rd
FAU - Baskin, E P
AU  - Baskin EP
FAU - Appleby, S D
AU  - Appleby SD
FAU - Kothstein, T
AU  - Kothstein T
FAU - Gehret, J R
AU  - Gehret JR
FAU - King, S W
AU  - King SW
FAU - Remy, D C
AU  - Remy DC
FAU - Lynch, J J Jr
AU  - Lynch JJ Jr
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Bridged Bicyclo Compounds)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Cyclopropanes)
RN  - 0 (Potassium Channels)
RN  - A5VAY2U3R8 (tedisamil)
SB  - IM
MH  - Animals
MH  - Anti-Arrhythmia Agents/*pharmacology
MH  - Bridged Bicyclo Compounds/*pharmacology
MH  - *Bridged Bicyclo Compounds, Heterocyclic
MH  - Cyclopropanes/*pharmacology
MH  - Dogs
MH  - Electrocardiography
MH  - Female
MH  - Ferrets
MH  - Heart/*drug effects/physiology
MH  - Hemodynamics/drug effects
MH  - In Vitro Techniques
MH  - Male
MH  - Myocardial Ischemia/physiopathology
MH  - Papillary Muscles/drug effects/physiology
MH  - Potassium Channels/drug effects
MH  - Refractory Period, Electrophysiological/drug effects
EDAT- 1995/04/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1995/04/01 00:00
PHST- 1995/04/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1995/04/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1995 Apr;273(1):168-75.