The interpretation of drug effects on isolated atrial preparations is highly dependent on experimental design, specifically the strength of electrical stimulation.
Should not inform clinical phenoxybenzamine use; leaves open stimulation-dependent effects in atrial research models.
Abstract:Isolated left rat atria were stimulated at a frequency of 180 per min. An increase in the strength of electrical stimulation from threshold (11±2mA) to suprathreshold values (50 mA) caused an initial decrease followed by an increase in the amplitude of the contractions. On the basis of experiments with an adrenergic β‐receptor blocker, practolol 5±10−6M, and atropine 1.43 ± 10−6M, it was shown that suprathreshold stimulation released noradrenaline as well as acetylcholine (ACh) within the myocardium. The effect of phenoxybenzamine, an adrenergic α‐receptor blocker with an atropine‐like activity, was also tested. At threshold stimulation this drug (2.5±10−6M) caused no changes in contractile force, while at suprathreshold values a pronounced increase in the amplitude of the contractions was observed. This effect was probably, at least partly, due to a blockade of the ACh‐induced depression of atrial contractile force. It is concluded that the interpretation of drug effects on isolated atrial preparations depends on the design of the experiments such as the strength of the electrical stimulation.
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Refsum et al. (1974) studied this question.
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