A comparison of the influence of La3+, D600 and gentamicin on frequency-force relationships in isolated myocardium.

The capability of heart muscle to respond mechanically to changes in frequency of stimulation was studied in the absence and in the presence of La3+, D600 and gentamicin using left atrial preparations of guniea pigs. L3+ (0.5 x 10(-3) M) and gentamicin (1 x 10(-3) M) depressed the basal contractile state at 1.0 Hz by about 90% (EC90), and inhibited the positive inotropic response to increased driving rate throughout the frequency range that was studied (0.1--2.2 Hz). In contrast, a comparable concentration of D600 (1.05 x 10(-6) M) reduced inotropic responses to high rates of stimulation (> 1.4 Hz) more than responses to low rates (< 0.8 Hz). Muscles exposed briefly (20 min) to an EC90 of La3+ or D600 failed to regain 50% of basal inotropy after one h rinse in normal medium; whereas, muscle exposed to gentamicin recovered 50% inotropy in approximately 5 min. Effects of D600 and La3+ on the frequency-force relationship were not abolished after 1.5--2 h recovery of the muscles in normal solution, but the effects of gentamicin were easily removed by the same recovery procedures. These data indicate that: (1) the cardiodepressant actions of La3+ and D600 were poorly reversible after in vitro treatment, and these actions were manifested at cellular loci essential for normal contractile responses to changes in heart rate, and (2) the cardiac actions of gentamicin were reversible and could be differentiated from the more complex actions of both D600 and La3+.