CARDIOVASCULAR DEPRESSANT EFFECTS OF NEOMYCIN AND GENTAMICIN IN RHESUS MONKEYS

Abstract

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 μg, i.v.) or isoprenaline (0.5 μg, 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 antibiotics in a higher primate species, and suggest that this adverse response is related to an alteration of calcium ion function.