ABSTRACT
BACKGROUND: The objective of the present study was to investigate the effects of increasing doses of norepinephrine (NE) with or without arginine-vasopressin (AVP) on intestinal oxygen supply and jejunal mucosal tissue oxygen tension in an acute endotoxic pig model. METHODS: In this prospective, randomized, experimental study on 24 domestic pigs, jejunal mucosal tissue PO2 (PO2muc) was measured using two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular haemoglobin (HbO2j) was determined by tissue reflectance spectrophotometry. Systemic haemodynamic variables, mesenteric-venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after Escherichia coli lipopolysaccharide (LPS) administration, and at 20 min intervals during incremental NE infusion (0.05, 0.1, 0.5, 1.0, and 2 microg kg(-1) min(-1), respectively) with 57 mU kg(-1) h(-1) AVP (n=8; NE+AVP group) or without (n=8; NE group); or infusion of an equal amount of normal saline (n=8; CON group). RESULTS: LPS infusion led to a significant (P<0.05) decrease of PO2muc and HbO2j. Both NE and NE+AVP increased arterial pressure, cardiac output, and mesenteric artery blood flow. Concomitant to an increase in systemic oxygen delivery, NE improved PO2muc and HbO2j. NE alone was superior in restoration of PO2muc when compared with NE+AVP. CONCLUSIONS: Both NE and NE+AVP improved global haemodynamics and systemic oxygen transport variables when compared with control animals in an acute endotoxic pig model. NE improved jejunal PO2muc at all dosages. NE effects were significantly blunted by simultaneous administration of AVP.
Subject(s)
Arginine Vasopressin/pharmacology , Endotoxemia/blood , Intestinal Mucosa/drug effects , Jejunum/drug effects , Norepinephrine/antagonists & inhibitors , Vasoconstrictor Agents/pharmacology , Acute Disease , Animals , Disease Models, Animal , Endotoxemia/physiopathology , Female , Hemodynamics/drug effects , Intestinal Mucosa/blood supply , Jejunum/blood supply , Male , Microcirculation/drug effects , Norepinephrine/pharmacology , Oxygen/blood , Oxygen Consumption/drug effects , Partial Pressure , Sus scrofaABSTRACT
BACKGROUND: The objective of the present study was to investigate sublingual microvascular blood flow and microcirculatory haemoglobin oxygen saturation (Smc(O(2))) during cardiopulmonary bypass (CPB) using constant systemic blood flow but different perfusion pressures achieved by phenylephrine administration. METHODS: Fifteen patients undergoing coronary artery bypass grafting were enrolled in this pilot study. Systemic haemodynamics, oxygen transport variables, arterial and mixed venous blood gas analysis, and microcirculatory variables were determined after initiation of general anaesthesia, during CPB (systemic blood flow=2.4 litre m(-2)), after increasing perfusion pressure by 20 mm Hg with a continuous infusion of phenylephrine, and after termination of phenylephrine infusion. RESULTS: CPB immediately resulted in a significant (P<0.05) decrease in systemic oxygen transport without alterations in sublingual microcirculatory blood flow and Smc(O(2)). Increasing perfusion pressure from 47 (SD 9) to 68 (7) mm Hg using phenylephrine=1.4 (1.0) microg kg(-1) min(-1) resulted in a significant decrease in sublingual small vessel blood flow (from median 2.5 to 1.8 arbitrary units) representing mostly capillary blood flow, but not in medium-sized vessels (median 3 to 2.8 arbitrary units). Concurrently, global tissue blood flow from 110 (54) to 197 (100) perfusion units and Smc(O(2)) increased from 72 (11)% to 84 (7)%, suggesting significant microcirculatory blood flow shunting in vessels with diameters >25 microm. CONCLUSIONS: Our data demonstrate that an increased perfusion pressure produced by phenylephrine at constant CPB flow may decrease microcirculatory blood flow in the sublingual mucosal microcirculation due to microvascular blood flow shunting.
