A comparison of josamycin with macrolides and related antibiotics on isolated rat atria.

The effects of macrolide (Josamycin, erythromycin, spiramycin and oleandomycin) and related antibiotics (clindamycin and lincomycin) were examined and compared in spontaneously beating right atrial preparations and in electrically driven left atrial preparations of rats. Josamycin and erythromycin (10(-7)-10(-4) M) produced a dose-dependent decrease in rate. contractile force and maximum following frequency and prolonged the sinus node recovery time and the refractory period. The negative inotropic effect of josamycin was not modified by pretreating the atria with atropine or with a mixture of antagonists containing phentolamine, practolol, diphenhydramine, cimetidine, methysergide and indomethacin. In isolated right atria, josamycin did not block the positive inotropic and chronotropic responses to isoprenaline but shifted the dose-response curve to Ca to the right. Josamycin and erythromycin reduced in a dose-dependent manner the slow responses induced in K-depolarized right atria by isoprenaline but this effect was reversed by increasing the Ca concentration in the bathing media. These findings demonstrate a direct negative inotropic effect of josamycin and suggest that this effect could in some way be explained by inhibiting transmembrane Ca influx into atrial cells. The clinical significance of these results is discussed.