An investigation of the cardiotoxic action of vancomycin in the isolated working rat heart

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The mechanism of cardiotoxic action of vancomycin was examined in preparations of isolated working rat hearts and spontaneously beating right atria. Vancomycin produced a concentration-dependent decrease in aortic flow, coronary flow and heart rate in the isolated working rat heart, with no significant effect on other haemodynamic parameters. At 5 m m, vancomycin produced a statistically significant decrease (compared with control values) in aortic flow (24.1 ± 7.5%) and in the basal heart rate (34.3 ± 3.5%) after 15 min incubation. Coronary flow was also reduced by 23.5 ± 9.2%. Prolonged exposure of the preparation to 5 m m-vancomycin produced a marked time-dependent bradycardia accompanied by a time-dependent increase in the leakage of lactic dehydrogenase (LDH) into the perfusion medium. Moreover, a correlation ( r = −0.94) was found between the time-dependent bradycardia and LDH leakage induced by Vancomycin. In the isolated spontaneously beating right atria pretreated with atropine, vancomycin (5 m m) also produced a time-dependent bradycardia similar to that found in the isolated working rat heart. Moreover, 45Ca 2+-flux studies indicated that vancomycin had no significant effect on the 45Ca 2+ uptake into the right atrial muscle. These data suggest that: (1) vancomycin has a direct and acute cardiotoxic action at high concentrations (> 1 m m); (2) time-dependent bradycardia is a sensitive functional index for the cardiotoxicity induced by vancomycin; (3) the bradycardia elicited by vancomycin is due neither to the release of acetylcholine from the parasympathetic nerves innervating the heart nor to blockade of Ca 2+ entry.