Cardiovascular depressant effects of neomycin and gentamicin in rhesus monkeys

1. The acute cardiovascular effects of neomycin and gentamicin, representative aminoglycoside antibiotics, were examined in surgically-prepared anaesthetized rhesus monkeys. 2. Intravenous administration of 14, 28, and 56 mg/kg of neomycin consistently induced a dose-dependent depression of systemic blood pressure, cardiac output, left ventricular contractile force, maximum dF/dt of left ventricular contraction, and heart rate. Neomycin produced similar cardiovascular depressant effects when heart rate was maintained constant by electrical pacing. 3. Maximum depression of haemodynamic values usually occurred within 2 to 5 min after injection of neomycin; values then gradually returned to control levels within 20 to 30 (14 mg/kg) or 60 to 80 (56 mg/kg) minutes. 4. Injection of CaCl2 (1.35 mEq Ca2+/kg, i.v.) during the peak depressant effect of neomycin produced a rapid and maintained restoration of cardiovascular function to control levels; conversely, noradrenaline (2 mug, i.v.) of isoprenaline (0.5 mug, i.v.) produced only transient reversal of the neomycin effects. 5. Similar evidence of cardiovascular dysfunction was observed with gentamicin. 6. These findings demonstrate the direct cardiovascular depressant effects of aminoglycoside natibiotics in a higher primate species, and suggest that this adverse response is related to an alteration of calcium ion function.