Differential Effects of Selective and Nonselective Potassium Channel Inhibitors in Ovine Endotoxemic Shock (Macrocirculation) and in a Rat Model of Septic Shock (Microcirculation)

BACKGROUND:Potassium-(K)-channel inhibitors may increase systemic vascular resistance in vasodilatory shock states. OBJECTIVE:The purpose of the present study was to compare the macro- and microvascular effects of the adenosine triphosphate-sensitive K-channel-(KATP)-inhibitor glipizide and the nonselective K-channel inhibitor tetraethylammonium (TEA) in ovine endotoxemic shock and septic shock in rats. DESIGN:Two randomized, controlled laboratory studies. ANIMALS:Thirty female sheep and 40 male Sprague Dawley rats. SETTING:Animal research facility INTERVENTION:Systemic hemodynamics were analyzed in ovine endotoxemic shock with guideline-oriented supportive therapy. Sheep were allocated to three treatment groups for 12 hglipizide 10 mg kg·h, TEA 8 mg kg·h, or 0.9% saline. The microvascular effects of each drug were evaluated in septic rats (cecal ligation and puncture model) receiving a 2-h infusion of each study drugglipizide 20 mg kg·h; TEA 50 mg kg·h, or 0.9% saline, respectively, followed by intravital microscopy of villi microcirculation. RESULTS:Compared with the control group, glipizide infusion increased systemic vascular resistance index and decreased cardiac index and heart rate (HR) in sheep (P