PMID- 7673081
OWN - NLM
STAT- MEDLINE
DCOM- 19951017
LR  - 20191031
IS  - 0910-8327 (Print)
IS  - 0910-8327 (Linking)
VI  - 10
IP  - 3
DP  - 1995
TI  - Digoxin-induced ventricular arrhythmias in the guinea pig heart in vivo: evidence 
      for a role of endogenous catecholamines in the genesis of delayed 
      afterdepolarizations and triggered activity.
PG  - 119-27
AB  - The mechanisms of digoxin-induced ventricular arrhythmias were studied in vivo 
      using a novel experimental model. Anesthetized guinea pigs were instrumented with 
      custom-made electrode catheters which enabled the monitoring and recording of 
      right atrial, right ventricular, and His bundle electrograms, midmyocardial 
      monophasic action potentials (MAP), and systemic arterial blood pressure. 
      Intravenous digoxin induced ventricular arrhythmias ranging from ventricular 
      premature contractions (VPCs) to ventricular fibrillation (VF). These were 
      associated with delayed afterdepolarizations (DADs) observed on the MAP 
      recordings. The severity of the arrhythmias depended on the dose of digoxin. 
      Short bursts of ventricular pacing neither terminated nor suppressed episodes of 
      ventricular tachycardias (VTs). A direct relationship existed between the paced 
      ventricular cycle length and the coupling interval between the last paced beat 
      and the first ectopic beat (r = 0.913, P < 0.001, n = 10) and between the 
      amplitude of the DADs and the pacing rate (r = 0.972, P < 0.05, n = 7). The 
      increased contractility (LV dp/dt) and heart rate evoked by isoproterenol (0.1 
      microgram/kg) did not induce DADs in the absence of digoxin. Verapamil terminated 
      the digoxin-induced VTs in 15 of 16 animals and abolished the associated DADs in 
      7 of 7 animals. Adenosine terminated the VTs in 15 of 19 animals and abolished 
      the DADs in 8 of 10 animals. Digoxin induced VT in only 1 of 6 animals treated 
      with reserpine (5 + 5 mg/kg) 24 and 48h prior to experimentation. However, 
      subsequent intravenous isoproterenol (0.2 micrograms/kg) induced VT and DADs, 
      both of which were abolished by verapamil, in all 6 animals.(ABSTRACT TRUNCATED 
      AT 250 WORDS)
FAU - Xu, J
AU  - Xu J
AD  - Likoff Cardiovascular Institute, Medical College of Pennsylvania, Philadelphia, 
      USA.
FAU - Hurt, C M
AU  - Hurt CM
FAU - Pelleg, A
AU  - Pelleg A
LA  - eng
GR  - HL43006/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Japan
TA  - Heart Vessels
JT  - Heart and vessels
JID - 8511258
RN  - 0 (Catecholamines)
RN  - 73K4184T59 (Digoxin)
RN  - 8B1QWR724A (Reserpine)
RN  - 9Y8NXQ24VQ (Propranolol)
RN  - CJ0O37KU29 (Verapamil)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Arrhythmias, Cardiac/chemically induced/*physiopathology
MH  - Catecholamines/*physiology
MH  - Digoxin
MH  - Disease Models, Animal
MH  - Electrocardiography
MH  - Female
MH  - Guinea Pigs
MH  - Male
MH  - Propranolol/pharmacology
MH  - Random Allocation
MH  - Reserpine/pharmacology
MH  - Ventricular Dysfunction/*physiopathology
MH  - Verapamil/pharmacology
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.1007/BF01744478 [doi]
PST - ppublish
SO  - Heart Vessels. 1995;10(3):119-27. doi: 10.1007/BF01744478.