HIGH-ENERGY PHOSPHATES IN HEART, LIVER, KIDNEY, AND SKELETAL-MUSCLE OF ENDOTOXEMIC RATS

Endotoxemia can affect the storage of high-energy phosphates [ATP, cre atine phosphate (CrP)] even in organs in which global blood flow does not fall. If a decrease in this storage is due to an inadequate oxygen supply-to-demand ratio, improving the perfusion should restore it. Th erefore, in anesthetized endotoxemic rats we studied organ perfusion a nd the storage of high-energy phosphates of heart, liver, kidney, and skeletal muscle and measured the effects of improving cardiac output ( CO) and organ blood flow with cardiostimulatory drugs [dopexamine (DX) and dobutamine (DB)]. Endotoxin (Escherichia coli O127.B8, 8 mg/kg) w as infused from 0 to 60 min in three groups of anesthetized rats: one untreated (saline only) group (ES; n = 10), and two groups in which we infused DX (3 x 10(-8) mol.kg(-1) min(-1); n = 10) or DB (10(-7) mol. kg(-1).min(-1); n = 8) from 60 to 135 min. A fourth group served as ti me-matched controls (C; n = 8). Organ blood flows at 0 and 135 min (en d of experiment) were measured with radioactive microspheres. In biops ies (at 135 min) we measured lactate, ATP, and CrP concentrations. End otoxemia decreased CO (45% at 135 min; P < 0.05), which could be resto red by DX and DB. Myocardial and skeletal muscle blood flow and ATP di d not differ in the groups at 135 min. Hepatic and renal blood flow de creased in the ES group 44 and 52%, respectively (P < 0.05); DX restor ed the fall of hepatic and DB of renal blood flow. Tissue lactate conc entration followed serum lactate levels: low in C, high in ES, and int ermediate in DB and DX groups. High-energy phosphate content suffered during endotoxemia: in heart and skeletal muscle CrP, and in liver and kidney ATP and CrP, had decreased; DB and DX restored CrP in heart, s keletal muscle, and kidney; moreover, DX improved ATP in liver and kid ney. Our results indicate that endotoxin administration resulted in a dissociation between tissue blood flow and ATP and CrP, which was not identical in the tissues studied.