Differential effects of a selective inhibitor of soluble guanylyl cyclase on global and regional hemodynamics during canine endotoxic shock.
Activation of soluble guanylyl cyclase (sGC) might occur early during septic shock and play a role in the regulation of vascular tone and the redistribution of blood flow. The aim of this study was to assess the effects of sGC inhibition with oxadiazoloquinoxalinone (ODQ) on global and regional hemodynamic parameters in a clinically relevant model of septic shock. Fifteen anesthetized adult mongrel dogs were equipped with femoral and pulmonary artery catheters and ultrasonic flow probes around the mesenteric, femoral and renal arteries. The animals were randomized to receive Escherichia coli endotoxin (2 mg/kg, i.v.) alone, endotoxin followed by ODQ (1 mg/kg i.v.), or ODQ alone. Endotoxin administration was followed by decreases in mean arterial pressure, cardiac index, mesenteric, renal and femoral blood flows (MBF, RBF and FBF), and increases in systemic and pulmonary vascular resistances. Fluid resuscitation restored cardiac index, systemic vascular resistance, pulmonary vascular resistance, MBF, RBF and FBF to pre-endotoxin levels. In the presence of endotoxin, ODQ administration increased MBF and prevented the restoration of FBF. Hence, selective inhibition of sGC may increase splanchnic blood flow in septic shock.
Preiser
Jean-Charles
JC
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
Sun
Qinghua
Q
Hadj-Sadok
Damien
D
Vincent
Jean-Louis
JL
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase; D006439:Hemodynamics / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow / Q000187:drug effects; D017597:Renal Blood Flow, Effective / Q000187:drug effects; D012772:Shock, Septic / Q000503:physiopathology*; D000071756:Soluble Guanylyl Cyclase; D014655:Vascular Resistance / Q000187:drug effects
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010069:Oxadiazoles; D011810:Quinoxalines; D018160:Receptors, Cytoplasmic and Nuclear; C482199:lipopolysaccharide, E coli O55-B5; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase