Potentiating paired stimulation of cardiac muscle in vitro as positive inotropic reference standard

In rabbit papillary muscles, potentiating paired stimulation was used as a standard positive inotropic intervention. Pairs of depolarizing electrical stimuli were applied, equal in strength and with a coupling interval of the functional refractory period plus 10 msec. After five successive pairs at a basic driving rate of 0.5 Hz, maximum potentiation amounting to a two- to threefold increase in the contraction amplitude was reached. The potentiating paired stimulation was rapid in both onset and reversibility and was reproducible. Potentiating paired stimulation is sparing since internal Ca2+ pools are utilized to increase force. Using potentiating paired stimulation-induced increase in force of contraction as a new reference, the following order of potency of positive inotropic agents was obtained: ouabain greater than DPI 201-106 greater than IBMX greater than APP 201-533. Effects of these drugs on rested-state contractions and frequency-force relationship were also investigated.