4-Aminopyridine, A Blocker of Voltage-Dependent K+ Channels, Restores Blood Pressure and Improves Survival in the Wistar Rat Model of Anaphylactic Shock

Objectives: Anaphylactic shock is associated with severe hypotension. Potassium channel blockers, such as 4-aminopyridine, induce vasoconstriction. The objective of this study was to test the ability of 4-aminopyridine to restore blood pressure and increase survival in anaphylactic shock. Design: Experimental study. Setting: Physiology laboratory. Subjects: Adult male Wistar rats. Interventions: Rats were sensitized with ovalbumin (1 mg SC), and anaphylactic shock was induced by IV injection of ovalbumin (1 mg). Experimental groups included non-allergic rats (NA) (n = 6); allergic rats (Controls) (n = 6); allergic rats treated with 4-aminopyridine (4-aminopyridine) (1 mg/kg) (n = 6); and allergic rats treated with epinephrine (EPI) (10 mu g/kg) (n = 6). Treatments were administered 1 minute after induction of anaphylactic shock. Measurements and Main Results: Mean arterial blood pressure, heart rate, and survival were measured for 60 minutes. Plasma levels of histamine, leukotriene B-4, prostaglandin E-2, prostaglandin F-2, pH, and Hco(3) were measured. Mean arterial blood pressure was normal in the NA group; severe hypotension and high mortality were observed in controls; normalization of mean arterial blood pressure, heart rate, and increased survival were observed in 4-aminopyridine and EPI groups. All allergic 4-aminopyridinetreated rats survived after the induction of anaphylactic shock. Histamine level was higher in controls and the 4-aminopyridine group but reduced in the EPI group. Prostaglandin E-2 increased in controls and EPI group and decreased in 4-aminopyridine group; prostaglandin F-2 increased in controls but decreased in 4-aminopyridine and EPI groups. Leukotriene B-4 decreased in 4-aminopyridine and EPI groups. Metabolic acidosis was prevented in the 4-aminopyridine group. \ Conclusions: Our data suggest that voltage-dependent K+ channel inhibition with 4-aminopyridine treatment restores blood pressure and increases survival in the Wistar rat model of anaphylactic shock. 4-aminopyridine or related voltage-dependent K+ channel blockers could be a useful additional therapeutic approach to treatment of refractory anaphylactic shock.