Adams H R, Durrett L R
J Clin Invest. 1978 Aug;62(2):241-7. doi: 10.1172/JCI109122.
Cardiac dysfunction is occasionally detected in patients undergoing treatment with amino-glycoside antibiotics, however, the mechanism responsible for the negative inotropic effect of these agents has not been identified. In the present investigation electrically driven left atria of guinea pigs were used to study the effects of gentamicin on calcium ion (Ca++)-dependent contractile events in heart muscle isolated from in vivo influences. When atria were first inactivated by excess potassium ion (K+; 22mM) and contractions were then restored by isoproterenol (an experimental model that accentuates the contractile dependence of myocardial fibers on influx of Ca++ through specific "slow channels" of the sarcolemma), the cardiac depressant activity of gentamicin (0.1 mM) was profoundly augmented. Conversely, the negative inotropic effect of tetrodotoxin (23.5 micron) was abolished by the same experimental conditions. Also, gentamicin (1 mM) and La+++ (0.5 mM) markedly decreased the positive inotropic response to increased frequency of stimulation; whereas, D600 (1.05 micron) converted the positive frequency-force relationship to a negative relationship. Present data indicate a direct cardiac depressant action of gentamicin, and suggest that this antibiotic adversely affects either the transport system responsible for Ca++ movement through slow channels of the sarcolemma, the availability of Ca++ for translocation to these sites, or both.
在接受氨基糖苷类抗生素治疗的患者中偶尔会检测到心脏功能障碍，然而，这些药物负性肌力作用的机制尚未明确。在本研究中，使用豚鼠的电驱动左心房来研究庆大霉素对离体心肌中钙离子（Ca++）依赖性收缩事件的影响。当心房首先被过量钾离子（K+；22mM）灭活，然后通过异丙肾上腺素恢复收缩时（该实验模型可增强心肌纤维对通过肌膜特定“慢通道”流入的Ca++的收缩依赖性），庆大霉素（0.1mM）的心脏抑制活性显著增强。相反，相同的实验条件消除了河豚毒素（23.5微米）的负性肌力作用。此外，庆大霉素（1mM）和La+++（0.5mM）显著降低了对刺激频率增加的正性肌力反应；而D600（1.05微米）则将正性频率-力关系转变为负性关系。目前的数据表明庆大霉素具有直接的心脏抑制作用，并提示这种抗生素对负责Ca++通过肌膜慢通道移动的转运系统、Ca++转运至这些位点的可用性或两者都有不利影响。
