High-energy phosphates in heart, liver, kidney, and skeletal muscle of endotoxemic rats
Van Lambalgen, A.A.; van Kraats, A.A.; Mulder, M.F.; Teerlink, T.; van den Bos, G.C.
American Journal of Physiology 266(4 Pt 2): H1581-H1587
1994
ISSN/ISBN: 0002-9513 PMID: 8184937 Document Number: 423736
Endotoxemia can affect the storage of high-energy phosphates (ATP, creatine 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. Therefore, in anesthetized endotoxemic rats we studied organ perfusion and 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 0127.B8, 8 mg/kg) was 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 times 10-8 mol cntdot kg-1 cntdot min-1; n = 10) or DB (10-7 mol cntdot kg-1 cntdot min-1; n = 8) from 60 to 135 min. A fourth group served as time-matched controls (C; n = 8). Organ blood flows at 0 and 135 min (end of experiment) were measured with radioactive microspheres. In biopsies (at 135 min) we measured lactate, ATP, and CrP concentrations. Endotoxemia decreased CO (45% at 135 min; P lt 0.05), which could be restored by DX and DB. Myocardial and skeletal muscle blood flow and ATP did not differ in the groups at 135 min. Hepatic and renal blood flow decreased in the ES group 44 and 52%, respectively (P lt 0.05); DX restored the fall of hepatic and DB of renal blood flow. Tissue lactate concentration followed serum lactate levels: low in C, high in ES, and intermediate 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, skeletal muscle, and kidney; moreover, DX improved ATP in liver and kidney. 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.