Dobutamine-induced spontaneous rhythmic contractions of human isolated atrial strips mimic physiological responses of intact human heart.
We have shown that in isolated human atrial strips the β1-adrenoceptor agonist dobutamine can induce spontaneous, stable and durable rhythmic contractions. The amplitude and frequency of these contractions were regulated endogenously by the tissue. We tested whether the spontaneously contracted atrial strips could be used as an experimental assay model to determine inotropic and chronotropic effects of existing drugs and candidate chemicals directly on human heart muscle. The well-established inotropic and chronotropic effects of the calcium channel blocker (verapamil), the β-adrenoceptor blocker (propranolol), the phosphodiesterase inhibitor (theophylline) and the Na(+)/K(+)-ATPase inhibitor (ouabain) were tested on spontaneously contracting strips of human atrium. With demonstrative tracings, we showed the negative inotropic and chronotropic effects of verapamil and propranolol, the positive inotropic and chronotropic effects of theophylline and the transient inotropic and tachyarrhythmic effects of ouabain on dobutamine-pretreated human atrial strips. By using this method the undetermined inotropic and chronotropic effects of any candidate compound can be evaluated directly on spontaneously contracting human atrial muscle. Furthermore, we demonstrated the advantages of using dobutamine instead of conventional electrical field stimulation in order to obtain stable and durable contractions of the atrial strips. In conclusion, we describe a new, simple, reliable, convenient and ethical method for investigating the inotropic and chronotropic effects of candidate drugs directly on human atrium tissue without the need for human test subjects.
Department of Pharmacology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey. aydan@gop.edu.tr
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Yenisehirli
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Elalmis
D002316:Cardiotonic Agents / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D015203:Reproducibility of Results
D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D004280:Dobutamine