Increased plasma tetrahydrobiopterin in septic shock is a possible therapeutic target

Abstract Hemoperfusion with a column of polymyxin B immobilized on fibers (PMX) has been used to adsorb endotoxin in-patients with septic shock. PMX hemoperfusion (PMX-H) increases blood pressure (BP) too rapidly for the effect to be attributable to endotoxin removal. Since inducible NO synthase (iNOS) is known to be involved in the profound hypotension, we hypothesized that a decrease of tetrahydrobiopterin (BH 4 ), an essential cofactor of iNOS, might account for the rapid effect of PMX-H on BP, if plasma BH 4 is increased concomitantly with NO in septic shock patients and if PMX can decrease BH 4 . BH 4 was evaluated by measuring total biopterin, which can include derivatives of BH 4 by using high-performance liquid chromatography (HPLC). We confirmed that PMX fabric time dependently decreased total biopterin concentration in vitro. The plasma level of total biopterin in shock patients was indeed markedly elevated compared with that in volunteers (131.1±33.4 vs. 10.4±1.1 nM, n =5, P P 4 removal as a potential therapeutic target.