The effects of diphenylhydantoin on mechanical and electrical properties of isolated cat myocardium.

The effects of diphenylhydantoin (DPH) (4 X 10(-5) to 2 X 10(-4) M) on contractile activity and electrical properties were studied in isotonically shortening cat papillary muscles exposed to DPH. 1. DPH reduces amplitudes of contraction especially at low stimulation rates (6 to 12/min). At higher, more physiological rates the negative inotropic effect is comparatively small. 2. DPH accentuates the mechanical transients usually following step changes of frequency. 3. DPH reduces the maximum rate of depolarisation (MRD) of the normal action potential (AP) and slows conduction especially at high stimulation rates. AP duration is shortened especially at low stimulation rates. 4. In Ca-mediated "slow responses" DPH reduces MRD, overshoot and AP duration and abolishes the frequency-dependent alterations of these parameters. 5. The results suggest that the antiarrhythmic potency of DPH is due to a cooperative action on both the fast and the slow membrane channels. 6. It is speculated that DPH leads to an accumulation of Ca2+ within a "limited subsarcolemmal space" thereby decreasing the driving force for the slow inward current.