title: Enalaprilat improves systemic cardiovascular parameters and mesenteric blood flow during hypotensive resuscitation from hemorrhagic shock in dogs.
abstract: Resuscitative interventions that improve mesenteric perfusion without causing instability in systemic arterial pressures may be helpful for improving trauma patient outcomes. Blocking angiotensin II formation with enalaprilat may be such an intervention. Two questions were addressed in this two-part study investigating resuscitation from hemorrhagic shock in dogs: Can systemic arterial pressures be maintained while administering a constant rate infusion of enalaprilat during resuscitation, and can enalaprilat improve cardiovascular status during resuscitation? Animals were hemorrhaged to a mean arterial pressure (MAP) of 40 to 45 mmHg for 30 min and then 30 to 35 mmHg for 30 min. Group I (n = 5) was resuscitated to a MAP 60 to 65 mmHg with enalaprilat (0.02 mg/kg/h). Group II was resuscitated to a MAP 40 to 45 mmHg with (n = 5) or without (n = 5) enalaprilat. Resuscitation in both groups consisted of intermittent intravenous lactated Ringer's solution (60 mL/kg/h) to reach and maintain the target MAPs. Systemic arterial pressures were unaffected by enalaprilat during resuscitation in Group I, allowing us to proceed to the second study. During severely hypotensive resuscitation (Group II), systemic arterial pressures were also stable and enalaprilat administration was associated with increases (P < or = 0.02) in cardiac index (+1.2 L/min/m2), stroke volume index (SVI) (+14.5 mL/m2), superior mesenteric artery flow (+80 mL/min), stroke work (+561 mmHg/mL/m2), and left ventricular power output (+55.7 mmHg/L/min/m2). Corresponding increases were not observed in controls. We conclude that administration of a constant rate infusion of enalaprilat during resuscitation can be accomplished without causing a hypotensive crisis. Since enalaprilat significantly improved cardiovascular status including mesenteric perfusion even during intentional hypotension, it has potential value for improving the treatment of trauma patients.
authors.affiliation: Iowa Methodist Medical Center, Surgery Education Department and Trauma Research, Des Moines 50309, USA.
authors.forename: Piper
authors.initials: P
authors.lastname: Wall
authors.forename: Charisse
authors.initials: C
authors.lastname: Buising
authors.forename: LaRhee
authors.initials: L
authors.lastname: Henderson
authors.forename: Tyler
authors.initials: T
authors.lastname: Rickers
authors.forename: Alberto
authors.initials: A
authors.lastname: Cárdenas
authors.forename: Lisa
authors.initials: L
authors.lastname: Owens
authors.forename: Gregory
authors.initials: G
authors.lastname: Timberlake
authors.forename: Norman
authors.initials: N
authors.lastname: Paradise
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D015773:Enalaprilat / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced*; D012039:Regional Blood Flow / Q000187:drug effects; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*; D013152:Splanchnic Circulation / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D015773:Enalaprilat