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The effects of the novel anti‐anginal compound RS 43285 on myocardial conduction in the anaesthetized dog
Author(s) -
Allely Maxine C.,
Alps B.J.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11444.x
Subject(s) - verapamil , sinus rhythm , medicine , anesthesia , ventricle , cardiology , effective refractory period , heart rate , nifedipine , qrs complex , refractory period , atrial fibrillation , blood pressure , calcium
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‐dimethylphenyl)‐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 μg 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 μg 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 μg kg −1 and this dose also increased the interval to SA node recovery. 5 Verapamil did not effect I‐A or I‐V conduction. However, A‐V conduction was affected with a significant prolongation occurring at resting heart rate at 100–400 μg kg −1 and a 2:1 A‐V block in one dog at rest. During right atrial pacing verapamil significantly increased A‐V conduction at 50–400 μg kg −1 . All dogs exhibited a 2:1 A‐V conduction block at the highest frequency at 400 μg kg −1 .