ABSTRACT
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.
Subject(s)
Animals , Male , Dogs , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Escherichia coli Infections , Enalaprilat/pharmacology , Shock, Septic/therapy , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Blood Pressure/drug effects , Cardiac Output/drug effects , Disease Models, Animal , Enalaprilat/administration & dosage , Fluid Therapy/methods , Infusions, Intravenous , Lactic Acid/blood , Portal Vein/drug effects , Regional Blood Flow/drug effects , Resuscitation/methods , Severity of Illness IndexABSTRACT
Hypertonic saline resuscitation (HR, 7.5% NaCl, 4 ml/Kg) effectively reverts severe hemorrhage, but a central neural component is probvably involved in the survival response. This experiment examines the role of central angiotensinergic pathways in the hemorrhage-hypertonic resuscitation interaction. Severely bled (43ñ 2 ml/Kg) pentobarbital-anesthetized dogs with chromically imnplanted cerebral ventricular cannulae were resusucitated with 4 ml/Kg 7.5% NaCl, iv 10 min after intracerebroventricular injection of 0.5 ml normal saline (CT), 159 µg saralasin (in 0.5 ml saline, SR), or 10 mg captopril (in 0.5 ml salaine, 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 bradually decreased thereafter, base excess remaining ar severe metabolic acidosis levels throughout, al CT-and 8/10CP-treated dogs survived indefinitely,, with near normal arterial pressure, cardiac, index and base excess levels. It is there fore 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 virtuallly ineffective
Subject(s)
Animals , Male , Captopril/administration & dosage , Renin-Angiotensin System/drug effects , Resuscitation , Saline Solution, Hypertonic/therapeutic use , Saralasin/administration & dosage , Shock/therapy , Cardiac Output/drug effects , Injections, IntraventricularABSTRACT
We studied the effects of pretreatment with hypertonic solutions on the conduction disturbances and cardiac arrhythmias caused by iv injection of bupivacaine in anesthetized mongrel dogs. Bupivacaine was injected in doses of 3 ms/Kg and 6.5 mg/Kg. The hypertonic solutions used were 7.5% NaCl, 5.4% LiCi, 50% Glucose (5 ml/Kg and 20% mannitol (10 ml/Kg). Bupivacaine induced severe conduction disturbances, as reflected by significant increases in QRS complex duration, HV interval and IV interval, and severe hypertension. The arrhythmias observed wereÑ sinus node dysfunction, nonustained ventricular tachycardia, sustained ventriculara tachycardia and ventricular fibrillation. These effects were dose dependent, and were more evident with the higher dose of bupivacine. Among all the hypertonic sulutions tested, only 7.5% NaCl effectivelly protected against conduction disturbances and cardiac arrhythmias. These findings suggest an important role for socium overload in these situations and provide a potentially harmless tool for the treatment of anesthetic accidents with bupivacaine during regionalo anesthesia