Arginine vasopressin reduces intestinal oxygen supply and mucosal tissue oxygen tension

We investigated intestinal oxygen supply and mucosal tissue PO2 during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal segments in anesthetized pigs. Mucosal tissue PO2 was measured by employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Microvascular blood flow was assessed by laser-Doppler velocimetry. Systemic hemodynamic variables, mesenteric venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline and at 20-min intervals during incremental AVP infusion (n = 8; 0.007, 0.014, 0.029, 0.057, 0.114, and 0.229 IU.kg(-1).h(-1), respectively) or infusion of saline (n=8). AVP infusion led to a significant (P < .05), dose-dependent decrease in cardiac index (from 121 +/- 31 to 77 +/- 27 ml.kg(-1).min(-1) at 0.229 IU.kg(-1).h(-1)) and systemic oxygen delivery (from 14 +/- 3 to 9 +/- 3 ml.kg(-1).min(-1) at 0.229 IU.kg(-1).h(-1)) concomitant with an increase in systemic oxygen extraction ratio (from 31 +/- 4 to 48 +/- 10%). AVP decreased microvascular blood flow (from 133 +/- 47 to 82 +/- 35 perfusion units at 0.114 IU.kg(-1).h(-1)), mucosal tissue PO2 (from 26 +/- 7 to 7 +/- 2 mmHg at 0.229 IU.kg(-1).h(-1)), and microvascular hemoglobin oxygen saturation (from 51 +/- 9 to 26 +/- 12% at 0.229 IU.kg(-1).h(-1)) without a significant increase in mesenteric venous lactate concentration (2.3 +/- 0.8 vs. 3.4 +/- 0.7 mmol/l). We conclude that continuously infused AVP decreases intestinal oxygen supply and mucosal tissue PO2 due to a reduction in microvascular blood flow and due to the special vascular supply in the jejunal mucosa in a dose-dependent manner in pigs.     

Electron transport system activity and oxygen consumption of two amphibious isopods,epigean Ligia italica Fabricius and hypogean Titanethes albus (Koch), in air and water

Electron transport system (ETS) activity and oxygen consumption (i.e. respiration, R) were measured in two amphibious isopods, epigean Ligia italica and hypogean Titanethes albus. The measurements were made in air and in water to estimate the exploitation of metabolic potential for actual metabolism in the two media. Oxygen consumption was measured in animals in air before their transfer to water, in water and again after their transfer back to air. Both species showed greater oxygen consumption during submergence in water than in air. Although epigean L. italica had higher oxygen consumption and ETS activity than hypogean T. albus, both species exhibited high and variable ETS/R ratios. A high and variable ETS/R ratio is one of the characteristics of amphibious isopods that enables them to cope with specific environmental conditions in their habitats.     

Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes

Abstract

Brain butyrylcholinesterase (BChE) is an attractive target for drugs designed for the treatment of Alzheimer’s disease (AD) in its advanced stages. It also potentially represents a biomarker for progression of this disease. Based on the crystal structure of previously described highly potent, reversible, and selective BChE inhibitors, we have developed the fluorescent probes that are selective towards human BChE. The most promising probes also maintain their inhibition of BChE in the low nanomolar range with high selectivity over acetylcholinesterase. Kinetic studies of probes reveal a reversible mixed inhibition mechanism, with binding of these fluorescent probes to both the free and acylated enzyme. Probes show environment-sensitive emission, and additionally, one of them also shows significant enhancement of fluorescence intensity upon binding to the active site of BChE. Finally, the crystal structures of probes in complex with human BChE are reported, which offer an excellent base for further development of this library of compounds.     

Jejunal tissue oxygenation and microvascular flow motion during hemorrhage and resuscitation

The relationship between flow motion and tissue oxygenation was investigated during hemorrhage/retransfusion with and without dopamine in 14 pigs. During 45% bleed, jejunal microvascular hemoglobin O(2) saturation (HBjO(2)) and mucosal tissue Po(2) (Po(2)muc) were recorded in seven control and seven dopamine-treated animals. Mean arterial pressure and systemic O(2) delivery decreased during hemorrhage and returned to baseline after retransfusion. Hemorrhage decreased Po(2)muc from 33 +/- 2.8 to 13 +/- 1.6 mmHg and HBjO(2) from 53 +/- 4.9% to 32 +/- 3.9%, respectively, in control animals. During reperfusion, Po(2)muc and HBjO(2) remained low. Dopamine increased Po(2)muc from 28 +/- 4.3 to 45 +/- 4.6 mmHg and HBjO(2) from 54 +/- 5.7% to 69 +/- 1.5% and attenuated the decrease in Po(2)muc and HBjO(2) during hemorrhage. After retransfusion, dopamine restored Po(2)muc and HBjO(2) to baseline. Control animals developed rhythmic HBjO(2) oscillations with increasing amplitude (frequency, 4.5 to 7.6 cycles/min) and showed an inverse relationship between Po(2)muc and HBjO(2) oscillation amplitude. Dopamine prevented regular flow motion. The association between decreased Po(2)muc and increased oscillations in HBjO(2) after normalization of systemic hemodynamics and O(2) transport in control animals suggests a cause-and-effect relationship between low tissue Po(2) and flow motion activity within the jejunal microcirculation.