Salutary effects of two verapamil analogs in traumatic shock.

We studied the effects of two verapamil analogs, anipamil and ronipamil, in traumatic shock. Noble-Collip drum trauma produced a shock state characterized by an eight-fold increase in plasma cathepsin D activity, a 13-fold increase in the rate of plasma myocardial depressant factor (MDF) accumulation, and a survival time of 1.9 ± 0.1 hours. Neither verapamil analog had any significant effect on attenuating the shock-induced rise in plasma cathepsin D activity. However, both anipamil and ronipamil (p < 0.01) significantly blunted the rate of MDF accumulation in the plasma. In addition, these agents significantly inhibited proteolysis in vitro. Both analogs significantly prolonged survival time to 3.1 ± 0.6 h at 0.25 mg/kg (p < 0.05) and to 4.4 ± 0.3 h at 1.0 mg/kg (p < 0.001). Anipamil appears to provide a more potent protection in this shock model; however, both verapamil derivatives possess promising anti-shock potential.