title: Hypertonic saline resuscitation is prevented by intracerebroventricular saralasin but not by captopril.
abstract: Hypertonic saline resuscitation (HR, 7.5% NaCl, 4 ml/kg) effectively reverts severe hemorrhage, but a central neural component is probably involved in the survival response. This experiment examines the role of central angiotensinergic pathways in hemorrhage-hypertonic resuscitation interaction. Severely bled (43 +/- 2 ml/kg) pentobarbital-anesthetized dogs with chronically implanted cerebral ventricular cannulae were resuscitated with 4 ml/kg 7.5% NaCl, iv 10 min after intracerebroventricular injection of 0.5 ml normal saline (CT), 150 micrograms saralasin (in 0.5 ml saline, SR), or 10 mg captopril (in 0.5 ml saline, CP). All 10 SR-treated dogs died 2-6 h after HR. Their arterial pressure and cardiac index initially recovered to near pre-hemorrhage levels, but gradually decreased thereafter, base excess remaining at severe metabolic acidosis levels throughout. All CT- and 8/10 CP-treated dogs survived indefinitely, with near normal arterial pressure, cardiac index and base excess levels. It is therefore concluded that the inhibition of central angiotensinergic sites with the competitive antagonist saralasin effectively prevents survival after HR, whereas inhibition of angiotensin converting enzyme by captopril in cerebrospinal fluid is virtually ineffective.
authors.affiliation: Divisão de Experimentaçaõ, Hospital das Clínicas, Universidade de São Paulo, Brasil.
authors.forename: I T
authors.initials: IT
authors.lastname: Velasco
authors.forename: M
authors.initials: M
authors.lastname: Rocha-e-Silva
mesh_terms: D000818:Animals; D002216:Captopril / Q000008:administration & dosage*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D007276:Injections, Intraventricular; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects; D012151:Resuscitation; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012504:Saralasin / Q000008:administration & dosage*; D012769:Shock / Q000628:therapy*
chemical_list: D012462:Saline Solution, Hypertonic; D002216:Captopril; D012504:Saralasin