Key result
Gentamicin profoundly depressed contractile tension in guinea pig atria contracting under slow Ca++-activated conditions, suggesting it inhibits Ca++ influx through slow channels of the sarcolemma.
Why the study?
Does gentamicin depress cardiac contractility by blocking slow Ca++ channels in guinea pig atrial myocardium?
Does gentamicin depress cardiac contractility by blocking slow Ca++ channels in guinea pig atrial myocardium?
p-value: p=<0.001
Gentamicin exerts a direct cardiac depressant action, likely by interfering with Ca++ movement through slow channels of the sarcolemma.
Potential cardiac depression warrants monitoring in vulnerable patients; leaves open translation to human myocardium.
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.
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Adams et al. (1978) studied this question. Gentamicin vs. Control medium (5.4 mM K+) or no drug was evaluated on Isometric contractile tension and its first derivative (dT/dt) under slow Ca++ channel activation (p=<0.001). Gentamicin profoundly depressed contractile tension in guinea pig atria contracting under slow Ca++-activated conditions, suggesting it inhibits Ca++ influx through slow channels of the sarcolemma.
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