Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis.
Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min) and enalaprilat infusion (0.02 mg kg(-1) min(-1) for 60 min) in randomized groups. The following groups were studied: controls (fluid infusion, N = 4), E1 (enalaprilat infusion followed by fluid infusion, N = 5) and E2 (fluid infusion followed by enalaprilat infusion, N = 5). All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO), portal vein blood flow (PVBF), systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.
Rahal
L
L
Divisão de Experimentação, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
Garrido
A G
AG
Cruz
R J
RJ
Rocha e Silva
M
M
Poli-de-Figueiredo
L F
LF
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D015773:Enalaprilat / Q000008:administration & dosage / Q000494:pharmacology*; D004927:Escherichia coli Infections; D005440:Fluid Therapy / Q000379:methods; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D008297:Male; D011169:Portal Vein / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012151:Resuscitation / Q000379:methods; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000628:therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D019344:Lactic Acid; D015773:Enalaprilat