Intestinal Mucosal Perfusion Research Articles

Intestinal mucosal perfusion and integrity are maintained in hypotensive brain dead mice.

Brain death (BD) leads to complex hemodynamic and inflammatory alterations which may compromise organ perfusion and induce morphologic and functional damage in various organs. The intestine is particularly sensitive to hypoperfusion and donor hypotension usually precludes intestinal donation. Previous studies reported inflammatory intestinal changes following BD but information on mucosal integrity and perfusion are lacking. BD was induced in mice by inflating an epidural balloon catheter. Controls underwent only anesthesia and tracheostomy. Intestinal perfusion was assessed using laser Doppler flowmetry (LDF). Intestinal injury was assessed after 2h of BD by the Chiu-Park score and morphometry. Intestinal tight junction (TJ) proteins (claudin-1, claudin-3, occludin, tricellulin) as well as inflammatory activation (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) were also analysed and compared with a sham group. Although blood pressure decreased in BD mice, intestinal perfusion remained similar between BD and sham mice. Histologically, mucosal injury was absent/minimal and TJs appeared well maintained in both groups. BD may trigger intrinsic, autoregulatory mechanisms to preserve microvascular tissue perfusion and mucosal integrity in spite of mild hypotension.

Metabolic Tissue Swelling and Local Microcirculation in Splanchnic Artery Occlusion Shock: Implications for Critical Illness.

Trauma is a leading cause of death in the United States. Advancements in shock resuscitation have been disappointing because the correct upstream mechanisms of injury are not being targeted. Recently, significant advancements have been shown using new cell-impermeant molecules that work by transferring metabolic water from swollen ischemic cells to the capillary, which restores tissue perfusion by microcirculatory decompression. The rapid normalization of oxygen transfer improves resuscitation outcomes. Since poor resuscitation and perfusion of trauma patients also causes critical illness and sepsis and can be mimicked by ischemia-reperfusion of splanchnic tissues, we hypothesized that inadequate oxygenation of the gut during trauma drives development of later shock and critical illness. We further hypothesized that this is caused by ischemia-induced water shifts causing compression no-reflow. To test this, the superior mesenteric artery of juvenile anesthetized swine was occluded for 30 minutes followed by 8 hours of reperfusion to induce mild splanchnic artery occlusion (SAO) shock. One group received the impermeant polyethylene glycol 20,000 Da (PEG-20k) that prevents metabolic cell swelling, and the other received a lactated Ringer's vehicle. Survival doubled in PEG-20k-treated swine along with improved macrohemodynamics and intestinal mucosal perfusion. Villus morphometry and plasma inflammatory cytokines normalized with impermeants. Plasma endotoxin rose over time after reperfusion, and impermeants abolished the rise. Inert osmotically active cell impermeants like PEG-20k improve intestinal reperfusion injury, SAO shock, and early signs of sepsis, which may be due to early restoration of mucosal perfusion and preservation of the septic barrier by reversal of ischemic compression no-reflow. SIGNIFICANCE STATEMENT: Significant advancements in treating shock and ischemia have been disappointing because the correct upstream causes have not been targeted. This study supports that poor tissue perfusion after intestinal ischemia from shock is caused by capillary compression no-reflow secondary to metabolic cell and tissue swelling since selectively targeting this issue with novel polyethylene glycol 20,000 Da-based cell-impermeant intravenous solutions reduces splanchnic artery occlusion shock, doubles survival time, restores tissue microperfusion, and preserves gut barrier function.

Beneficial effect of capsaicin via TRPV4/EDH signals on mesenteric arterioles of normal and colitis mice

IntroductionAlthough capsaicin has long been used as food additive and medication worldwide, its actions on gastrointestinal tract as its most delivery pathway have not been well addressed. ObjectivesIn the present study, we aimed to study GI actions of capsaicin on mesenteric arterioles in normal and colitis mice and to elucidate the underlying mechanisms. MethodsVasorelaxation of human submucosal arterioles and the mesenteric arterioles from wide-type (WT) mice, TRPV1−/− and TRPV4−/− (KO) mice were measured. The expression and function of TRPV channels in endothelial cells were examined by q-PCR, immunostaining, Ca2+ imaging and membrane potential measurements. ResultsCapsaicin dose-dependently induced vasorelaxation of human submucosal arterioles and mouse mesenteric arterioles in vitro and in vivo through endothelium-dependent hyperpolarization (EDH), nitric oxide (NO), and prostacyclin (PGI2). Using TRPV1 and TRPV4 KO mice, we found that capsaicin-induced vasorelaxation was predominately through TRPV4/EDH, but marginally through TRPV1/NO/PGI2. Capsaicin induced hyperpolarization through activation of endothelial TRPV4 channels and intermediate-conductance of Ca2+-activated K+ channels to finally stimulate vasorelaxation. Importantly, capsaicin exerted anti-colitis action by rescuing the impaired ACh-induced vasorelaxation in WT colitis mice but not in TRPV4 KO colitis mice. ConclusionsCapsaicin increases intestinal mucosal blood perfusion to potentially prevent/treat colitis through a novel TRPV4/EDH-dependent vasorelaxation of submucosal arterioles in health and colitis. This study further supports our previous notion that TRPV4/EDH in mesenteric circulation plays a critical role in the pathogenesis of colitis.

Correlation of minimally invasive imaging techniques to assess intestinal mucosal perfusion with established markers of chronic inflammatory enteropathy in dogs.

BackgroundMinimally invasive diagnostic imaging techniques to detect intestinal inflammation in dogs are lacking. Contrast‐enhanced ultrasound (CEUS) and endoscopic narrow band imaging‐like endoscopy (Storz Professional Image Enhancement System [SPIES]) might allow quantification of intestinal mucosal perfusion and microvessel density in chronic inflammatory enteropathy (CIE) of dogs.Hypothesis/ObjectivesMarkers of mucosal perfusion as determined by CEUS and SPIES endoscopy are potentially useful diagnostic markers to help characterize CIE and correlate with histological inflammation type and severity.AnimalsThirty client‐owned dogs diagnosed with CIE at a referral hospital were prospectively enrolled.Materials and MethodsData from CEUS, SPIES, and white light (WL) endoscopy were correlated with World Small Animal Veterinary Association (WSAVA) endoscopy and histology scores and vessel density as determined by immunohistochemistry for von Willebrand factor (vWF). Automated linear modeling was used to determine predictors of endoscopic and histologic severity.ResultsDuodenal histology correlated with SPIES data (area percentage value, rho = 0.424, P = .04). White light endoscopy parameters correlated with SPIES parameters in the duodenum. Colonic histology correlated positively with CEUS, whereas colonic CEUS parameters correlated inversely with vWF expression. Several duodenal parameters combined predicted duodenal histology scores to a level of 73.4%. For the colon, 2 parameters contributed more than others to 73.1%.Conclusion and Clinical ImportanceMinimally invasive CEUS and SPIES appear feasible to assess intestinal perfusion in CIE. Use of SPIES endoscopy may be promising for assessing small intestinal inflammation, whereas CEUS could be used to assess colonic perfusion and inflammation. Both techniques need to be investigated further for their clinical utility.

Splanchnic Circulation and Intraabdominal Metabolism in Two Porcine Models of Low Cardiac Output

The impact of acute cardiac dysfunction on the gastrointestinal tract was investigated in anesthetized and instrumented pigs by sequential reductions of cardiac output (CO). Using a cardiac tamponade (n = 6) or partial inferior caval vein balloon inflation (n = 6), CO was controllably reduced for 1 h each to 75% (CO75%), 50% (CO50%), and 35% (CO35%) of the baseline value. Cardiac output in controls (n = 6) was not manipulated and maintained. Mean arterial pressure, superior mesenteric arterial blood flow, and intestinal mucosal perfusion started to decrease at CO50% in the intervention groups. The decrease in superior mesenteric arterial blood flow was non-linear and exaggerated at CO35%. Systemic, venous mesenteric, and intraperitoneal lactate concentrations increased in the intervention groups from CO50%. Global and mesenteric oxygen uptake decreased at CO35%. In conclusion, gastrointestinal metabolism became increasingly anaerobic when CO was reduced by 50%. Anaerobic gastrointestinal metabolism in low CO can be detected using intraperitoneal microdialysis.

Vascular Pathology of Ischemia/Reperfusion Injury of Rat Small Intestine

Ischemia/reperfusion (I/R) injury of the small intestine caused by occlusion of the superior mesenteric artery affects the intestinal tissue as well as components of the blood circulatory system from the microvasculature to mesenteric vessels. The aim of this work was to study the correlation between the dynamics of destruction development in the intestinal tissue, microvasculature, and mesenteric vessels in I/R of the small intestine. The microvasculature was analyzed by whole-organ continuous monitoring of the intestinal mucosal blood perfusion by laser Doppler flowmetry during the entire I/R. Real-time RT-PCR was used to assess gene expression of NF-κB, caspase-3, Ki67, and TNF-α in blood vessels. At the start of reperfusion, the first targets to be disrupted are microvessels in the apical villi. Injury of the apical part of the microcirculatory bloodstream correlates with the reduction in intestinal mucosal blood perfusion, which occurred simultaneously with apical villous destruction. By the end of the reperfusion period, the low intestinal mucosal blood perfusion is mirrored by the destruction of the microvasculature and mucosal structures in the entire organ. The development of mesenteric vessel injury is characterized by a change in NO metabolism and damaged endothelial cells concomitant with an alteration in the expression of genes encoding NF-κB, caspase-3, and Ki67 by the end of the reperfusion period. In I/R injury, detrimental effects on the intestinal tissue, microvasculature, and mesenteric vessels develop and exhibit common mechanisms of function, which show strong correlations.

Serum diamine oxidase as a hemorrhagic shock biomarker in a rabbit model.

BackgroundIn prolonged hemorrhagic shock, reductions in intestinal mucosal blood perfusion lead to mucosal barrier damage and systemic inflammation. Gastrointestinal failure in critically ill patients has a poor prognosis, so early assessment of mucosal barrier injury in shock patients is clinically relevant. Unfortunately, there is no serum marker that can accurately assess intestinal ischemia-reperfusion injury.ObjectiveThe aim of this study was to assess if serum diamine oxidase levels can reflect intestinal mucosal injury subsequent to prolonged hemorrhagic shock.MethodsThirty New Zealand white rabbits were divided into three groups: a control group, a medium blood pressure (BP) group (exsanguinated to a shock BP of 50 to 41 mm Hg), and a low BP group (exsanguinated to a shock blood pressure of 40 to 31 mm Hg), in which the shock BP was sustained for 180 min prior to fluid resuscitation.ResultsThe severity of hemorrhagic shock in the low BP group was significantly greater than that of the medium BP group according to the post-resuscitation BP, serum tumor necrosis factor (TNF)-α, and arterial lactate. Intestinal damage was significantly more severe in the low BP group according to Chiu’s scoring, claudin-1, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase expression. Serum diamine oxidase was significantly increased in the low BP group compared to the medium BP and control groups and was negatively correlated with shock BP.ConclusionSerum diamine oxidase can be used as a serological marker in evaluating intestinal injury and shows promise as an indicator of hemorrhagic shock severity.

Changes in Intestinal Mucosal Microvascular Perfusion Assessed Using Orthogonal Polarisation Spectral Imaging in the Horse

AimsAlthough several markers for measuring global tissue perfusion are available, there are currently no practical measurements of capillary microvascular perfusion in horses with hypovolaemia. Orthogonal polarisation spectral (OPS) imaging allows assessment of capillary microvascular perfusion by visualisation of mucosal blood flow. This study aims to demonstrate that administration of the α2 adrenoreceptor agonist detomidine, results in measurable changes in mucosal blood flow that can be determined using OPS. We hypothesise that these changes will mirror known aberrations in total peripheral resistance and cardiac output.MethodsMicrovascular blood flow was recorded using OPS placed manually, per rectum in 6 normal horses (weighing 603 ± 134 kg) undergoing sedation for a range of clinical procedures. The OPS recordings were made prior to and following sedation (5, 10, 20 min) with detomidine (10 ug/kg bwt) and butorphanol (10 ug/kg bwt) administered by i.v. injection. Microvascular perfusion was determined using standardised methods from OPS recordings including proportion of perfused vessels (PPV), functional capillary density (FCD), microvascular flow index (MFI) and vessel density (VD).ResultsDetomidine had a significant effect on microvascular blood flow as demonstrated by changes in MFI, PPV and FCD 5 min following sedation (P<0.001) and changes in VD 10 min after sedation (P<0.02). Microvasculature had returned to the presedation baseline by 20 min for all criterions.ConclusionsThese data demonstrate that changes in organ perfusion known to be caused by α2 adrenoreceptor agonists result in observable changes in mucosal blood flow. This appears to mirror changes in cardiac output and total peripheral resistance previously demonstrated after administration of detomidine in the horse.Practical significanceThis technique may be a useful marker to use in early goal‐directed therapy in horses with systemic inflammatory response syndrome (SIRS) and severe intestinal pathology.AcknowledgementsThe staff at DAC Melton Mowbray for their assistance with the conduct of the study.Ethical animal researchThis study was approved by the University of Nottingham ethical review committee. Horses were admitted into the DAC veterinary facility for routine veterinary procedures and sedated for routine dental care or orthopaedic investigation. Full consent was given by the DAC for use of these horses in the study. Sources of funding: Student project undertaken at the University of Nottingham. Competing interests: None.

The effect of valproic acid in alleviating early death in burn shock

The aim of this study was to examine whether administration of valproic acid (VPA) improves blood circulation and survival after lethal burn shock. Forty adult male Beagle dogs underwent a 50% TBSA full-thickness flame injury. In the first 24 h after burn, animals were randomly divided into four groups: NR group received no treatment. VPA group and 2M2P(2-methyl-2-pentenoic acid) group received either VPA or 2M2P (100 mg of the either drug in 20 mL of normal saline) intravenously. VR group received intravenous infusion of lactated Ringer's solution according to Parkland formula. In the second 24 h after burn the animals of all groups received delayed IV fluid resuscitation. Hemodynamic variables and biochemical parameters were determined with animals in the conscious and cooperative state. From 4 h after burn on, the levels of mean arterial pressure, cardiac index, plasma volume and intestinal mucosal blood perfusion in VPA group were significantly higher, and the levels of parameters of organ function and serum tumor necrosis factor-α were lower than those in NR group and 2M2P group (all P < 0.05). Survival at 72 h after burn was in following order: VR (100%) > VPA (60%) > 2M2P (30%) > NR (10%). Our results showed that histone deacetylace inhibitor (HDACI) valproic acid significantly improved hemodynamics, intestinal perfusion, and the survival rate after lethal burn shock. The mechanism may be attributable partly to the lowering of the level of proinflammatory factors, ameriolation of vasopermeability-induced visceral edema, reduction of blood volume loss, and protection of vital organs through inhibition of histone deacetylase activity of cell of vital organs.

Synthetic Atrial Natriuretic Peptide Improves Systemic and Splanchnic Circulation and Has a Lung-Protective Effect During Endotoxemia in Pigs

Pharmacological blockade of the renin-angiotensin system is thought to maintain gut perfusion during circulatory stress and thereby avoid later failure of distant organs. In this controlled experimental study, we investigated the effects of carperitide, a synthetic atrial natriuretic peptide that inhibits the renin-angiotensin system, on the systemic and splanchnic circulation during fluid-resuscitated endotoxemia in pigs. Sixteen domestic pigs of both sexes were randomly divided into 2 groups. The pigs were anesthetized and their lungs ventilated before receiving either saline (Group A: n = 8) or carperitide (Group B: n = 8). After a baseline measurement was taken, the pigs from both groups received a continuous infusion (1.7 microg x kg(-1) x h(-1)) of endotoxin for 240 min. Group B received a continuous infusion of carperitide (0.05 microg x kg(-1) x min(-1)) starting 30 min before the endotoxin infusion and lasting until the end of the study, whereas Group A received the same volume of saline. Fluid resuscitation was titrated to maintain pulmonary artery wedge pressure between 10 and 12 mm Hg. Systemic and regional hemodynamics, oxygenation variables, and the arterial-to-intestinal PCO(2) gap were measured at baseline and after endotoxin infusion for 240 min. The primary end points were cardiac index, superior mesenteric artery flow index, and PCO(2) gap at the end of this study (T240). Cardiac index and superior mesenteric artery flow index in Group B were significantly higher than those in Group A at T240 (83 +/- 15 vs 135 +/- 23 mL x kg(-1) x min(-1), P < 0.001; 2.6 +/- 1.4 vs 7.9 +/- 4.8, P = 0.01), respectively. Carperitide administration resulted in a significantly better maintenance of intestinal mucosal perfusion assessed by the PCO(2) gap at T240 (33.0 +/- 14.5 vs 11.6 +/- 10.0 mm Hg, P = 0.004). The PaO(2)/FIO(2) ratio in Group B was significantly greater than that in Group A from T60 to T240. In this porcine fluid-resuscitated endotoxemia model, a low dose of carperitide administered before endotoxemia maintained systemic and splanchnic circulation, and prevented the deterioration of oxygenation. Atrial natriuretic peptide infusion is a potentially beneficial therapy with respect to systemic and splanchnic circulation as well as the respiratory system during sepsis.

New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery

BackgroundGut barrier loss has been implicated as a critical event in the occurrence of postoperative complications. We aimed to study the development of gut barrier loss in patients undergoing major non-abdominal surgery.Methodology/Principal FindingsTwenty consecutive children undergoing spinal fusion surgery were included. This kind of surgery is characterized by long operation time, significant blood loss, prolonged systemic hypotension, without directly leading to compromise of the intestines by intestinal manipulation or use of extracorporeal circulation. Blood was collected preoperatively, every two hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (PrCO2, Pr-aCO2-gap). Plasma concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased rapidly and significantly after the onset of surgery in most children. Postoperatively, all markers decreased promptly towards baseline values together with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly negatively correlated with MAP at ½ hour before blood sampling (−0.726 (p<0.001), −0.483 (P<0.001), respectively). Furthermore, circulating I-FABP correlated with gastric mucosal PrCO2, Pr-aCO2-gap measured at the same time points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively).Conclusions/SignificanceThis study shows the development of gut barrier loss in children undergoing major non-abdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion. These data shed new light on the potential role of peroperative circulatory perturbation and intestinal barrier loss.

Ischemic Intestinal Injury during Cardiopulmonary Bypass Does Not Show an Association with Neutrophil Activation

Background: Neutrophil activation and tissue sequestration are crucial events in intestinal ischemia-reperfusion injury, but their role in the gut wall after clinical cardiopulmonary bypass (CPB) remains unclear. We tested whether local post-CPB inflammatory response in the gut wall would be associated with intestinal mucosal perfusion. Methods: Twenty pigs underwent 60 min of aortic clamping and 75 min of normothermic perfusion. Intestinal biopsies were taken after 120 min of reperfusion. Based on ileal myeloperoxidase activity (MPO), the animals were divided into 2 groups, CPB-induced increase in MPO (MPO+) versus no such increase (MPO–), for comparison of the parameters that measure gut mucosal perfusion. Ileal p_CO_₂ and intramucosal pH were determined, and arterial gases were analyzed. Additionally, several hemodynamic parameters and blood thrombin-antithrombin complexes (TAT) were measured. Results: Myocyte degeneration, endothelial activation and vasculitis were more pronounced in the MPO+ group (p < 0.05), while the MPO– group showed significantly increased pi_CO_₂ and lower mucosal pH values during reperfusion. Hemodynamics and TAT levels did not differ between the groups. Conclusion: Tissue sequestration of neutrophils was poorly associated with perturbed mucosal perfusion after CPB. Mechanisms of gut wall injury after a low-flow/reperfusion setting can differ from those in reperfusion injury after total ischemia.

Effect of Age, Feeding, and Omeprazole Administration on Gastric Tonometry in Healthy Neonatal Foals

Gastric tonometry is commonly used in humans as an assessment of intestinal mucosal perfusion. Values in healthy foals are currently unknown. Age, enteral feeding, and omeprazole administration would significantly alter gastric tonometry measurements in neonatal foals. Nine clinically normal foals were used to assess the effect of age and feeding, and 8 similar foals were used to assess the effect of omeprazole. At 1, 7, and 14 days of age, gastric intramucosal PCO2 (PgCO2) and arterial blood gas samples were obtained at baseline, immediately after feeding milk, and 1 and 2 hours after fasting for calculation of the intramucosal-arterial PCO2 difference (DeltaCO2). To evaluate the effect of omeprazole, foals were evaluated twice as above, 2 hours after fasting, comparing administration of omeprazole to no drug. There was a significant effect of age and feeding on PgCO2 and DeltaCO2, whereas arterial PCO2 was not significantly affected by these factors. Postfeeding DeltaCO2 values were significantly lower than fasted values. Baseline and postfeeding DeltaCO2 increased with age. There was no significant effect of age on data collected after 1 or 2 hours of fasting. The 90% reference interval for DeltaCO2 data collected after fasting was 0-54 mmHg. Foals had a significantly higher mean gastric pH and significantly higher DeltaCO2 and PgCO2 following omeprazole relative to no treatment. Because of the high and variable DeltaCO2, which is exacerbated by omeprazole administration, the reference interval in foals is extremely wide.

Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia*

To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. Controlled experimental study. University-based research laboratory. A total of 14 anesthetized, mechanically ventilated sheep. Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 microg/kg endotoxin, followed by 4 microg x kg(-1) x hr(-1) for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins. Endotoxin infusion decreased mean arterial blood pressure, cardiac output, and superior mesenteric artery blood flow (96 +/- 10 vs. 51 +/- 20 mm Hg, 145 +/- 30 vs. 90 +/- 30 mL x min(-1) x kg(-1), and 643 +/- 203 vs. 317 +/- 93 mL x min(-1) x kg(-1), respectively; p < .05 vs. basal), whereas it increased intramucosal-arterial PCO2 (deltaPCO2) and arterial lactate (3 +/- 3 vs. 14 +/- 8 mm Hg, and 1.5 +/- 0.5 vs. 3.7 +/- 1.3 mmol/L; p < .05). Sublingual, and serosal and mucosal intestinal microvascular flow indexes, and the percentage of perfused ileal villi were reduced (3.0 +/- 0.1 vs. 2.3 +/- 0.4, 3.2 +/- 0.2 vs. 2.4 +/- 0.6, 3.0 +/- 0.0 vs. 2.0 +/- 0.2, and 98% +/- 3% vs. 76% +/- 10%; p < .05). Resuscitation normalized mean arterial blood pressure (92 +/- 13 mm Hg), cardiac output (165 +/- 32 mL x min(-1) x kg(-1)), superior mesenteric artery blood flow (683 +/- 192 mL x min(-1) x kg(-1)), and sublingual and serosal intestinal microvascular flow indexes (2.8 +/- 0.5 and 3.5 +/- 0.7). Nevertheless, deltaPCO2, lactate, mucosal intestinal microvascular flow indexes, and percentage of perfused ileal villi remained altered (10 +/- 6 mm Hg, 3.7 +/- 0.9 mmol/L, 2.3 +/- 0.4, and 78% +/- 11%; p < .05). In this model of endotoxemia, fluid resuscitation corrected both serosal intestinal and sublingual microcirculation but was unable to restore intestinal mucosal perfusion. Intramucosal acidosis might be due to persistent villi hypoperfusion.

NOREPINEPHRINE AND INTESTINAL MUCOSAL PERFUSION IN VASODILATORY SHOCK AFTER CARDIAC SURGERY

Patients with norepinephrine-dependent vasodilatory shock after cardiac surgery (n = 10) were compared with uncomplicated postcardiac surgery patients (n = 10) with respect to jejunal mucosal perfusion, gastric-arterial PCO2 gradient, and splanchnic oxygen demand/supply relationship. Furthermore, the effects of norepinephrine-induced variations in MAP on these variables were evaluated in vasodilatory shock. Norepinephrine infusion rate was randomly and sequentially titrated to target MAPs of 60, 75, and 90 mmHg (0.25 +/- 0.24, 0.37 +/- 0.21, and 0.55 +/- 0.39 microg/kg per minute, respectively). Data on jejunal mucosal perfusion, jejunal mucosal hematocrit, and red blood cell (RBC) velocity (laser Doppler flowmetry) as well as gastric-arterial PCO2 gradient (gastric tonometry) and splanchnic oxygen and lactate extraction (hepatic vein catheter) were obtained. Splanchnic oxygen extraction was 71 +/- 16% in the vasodilatory shock group and 41 +/- 9% in the control group (P < 0.001), whereas splanchnic lactate extraction did not differ between the two groups. Jejunal mucosal perfusion (61%; P < 0.001), RBC velocity (35%; P < 0.01), and gastric-arterial mucosal PCO2 gradient (150%; P < 0.001) were higher in the vasodilatory shock group compared with those of the control group. Jejunal mucosal perfusion, jejunal mucosal hematocrit, RBC velocity, gastric-arterial mucosal PCO2 gradient, splanchnic oxygen extraction, and splanchnic lactate extraction were not affected by increasing infusion rates of norepinephrine. In patients with norepinephrine-dependent vasodilatory shock after cardiac surgery, intestinal mucosal perfusion was higher, whereas splanchnic and gastric oxygen demand/supply relationships were impaired compared with postoperative controls, suggesting that intestinal mucosal perfusion is prioritized in vasodilatory shock. Increasing MAP from 60 to 90 mmHg with norepinephrine in clinical vasodilatory shock does not affect intestinal mucosal perfusion and gastric or global splanchnic oxygen demand/supply relationships.

Effects of vasopressin (AVP) on intestinal mucosal perfusion in patients with norepinephrine-dependent vasodilatory shock after cardiac surgery

Effects of vasopressin (AVP) on intestinal mucosal perfusion in patients with norepinephrine-dependent vasodilatory shock after cardiac surgery

Thoracic epidural anesthesia improves intestinal mucosal capillary perfusion in acute oedematous pancreatitis in the rat

Thoracic epidural anesthesia improves intestinal mucosal capillary perfusion in acute oedematous pancreatitis in the rat

Autoregulation of Human Jejunal Mucosal Perfusion During Cardiopulmonary Bypass

Animal studies have suggested that autoregulation of intestinal blood flow is severely impaired during cardiopulmonary bypass (CPB). We investigated the jejunal mucosal capacity to autoregulate perfusion during nonpulsatile CPB (34 degrees C) in 10 patients undergoing elective cardiac surgery. Changes in mean arterial blood pressure (MAP) were induced by altering the CPB flow rate randomly for periods of 3 min from 2.4 L/min/m2 to either 1.8 or 3.0 L/min/m2. Jejunal mucosal perfusion (JMP) was continuously recorded by laser Doppler flowmetry. A typical pattern of flow motion (vasomotion) was recorded in all patients during CPB. Variations in CPB flow rates caused no significant changes in mean JMP, jejunal mucosal hematocrit, or red blood cell velocity within a range of MAP from 50 +/- 15 to 74 +/- 16 mm Hg. The vasomotion frequency and amplitude was positively correlated with CPB flow rate. IV injections of prostacyclin (10 microg, Flolan) blunted vasomotion and increased JMP from 192 +/- 53 to 277 +/- 70 (P < 0.05) perfusion units despite a reduction in MAP from 59 +/- 12 to 45 +/- 10 mm Hg (P < 0.05). Prostacyclin-induced vasodilation resulted in loss of mucosal autoregulation (pressure-dependent perfusion). We conclude that autoregulation of intestinal mucosal perfusion is maintained during CPB in humans.

Effects of systemically applied clonidine on intestinal perfusion and oxygenation in healthy pigs during general anaesthesia and laparotomy 1

Clonidine, which is used for induction of sympatholysis and prevention or treatment of alcohol withdrawal in anaesthesia and intensive care medicine, may have deleterious effects on intestinal mucosal perfusion. This study was designed to investigate the effects of clonidine on intestinal perfusion and oxygenation. Following ethical approval 17 anaesthetized, and acutely instrumented pigs were randomly assigned to two groups: eight animals received intravenous clonidine (2 microg kg(-1) bolus and 2 microg kg(-1) h(-1)), nine animals served as a control group. Measurement points for systemic and regional haemodynamic and oxygenation parameters were 135 and 315 min after starting the clonidine application. Clonidine elicited systemic haemodynamic changes (median [25-75th interquartile range]): heart rate (106 [91, 126] to 84 [71, 90] beats min(-1)) cardiac output (147 [123, 193] to 90 [87, 107] mL min(-1) kg(-1)) and mean arterial pressure (77 [72, 93] to 69 [61, 78] mmHg) decreased. Despite systemic haemodynamic changes, the superior mesenteric artery blood flow did not change in the clonidine group. The vascular resistance of the superior mesenteric artery decreased. The small intestinal oxygen supply, the mucosal and the serosal tissue oxygen partial pressure did not change. Systemic sympatholysis induced by intravenously applied clonidine in addition to basic intravenous anaesthesia elicited a decrease in cardiac output and mean arterial pressure. However, regional macrohaemodynamic perfusion was maintained and intestinal oxygenation did not change. Clonidine does not impair intestinal mucosal and serosal oxygenation under physiological conditions.

Monitoring of the Intestinal Mucosal Perfusion Using Laser Doppler Flowmetry After Multivisceral Transplantation

Background Graft endothelium constitutes a prime target during acute rejection. Infiltration of T cells, monocytes, and enhanced endothelial-leukocyte interactions result in microvascular impairment and altered perfusion. Materials and methods We measured mucosal blood flow using a laser Doppler flowmeter in three patients undergoing multivisceral transplantation. Thirty-seven measurements were performed through the ileostomy over the first 4 weeks posttransplantation. Most measurements were performed within a 24-hour interval from endoscopy and biopsy. Results Mucosal perfusion increased throughout the first postoperative week and eventually stabilized around levels specific for each patient. Mucosal perfusion remained stable during graft pancreatitis, but decreased 35% to 55% from baseline (the average value of the previous measurements) during acute rejection and sepsis. During the first week posttransplantation there was a gradual increase in mucosal perfusion, which might reflect regeneration after reperfusion injury. Increased mucosal perfusion did not seem to correlate with rejection or other adverse clinical events. A sudden decrease in mucosal perfusion of 30% or more compared to the previous measurements was associated with septic episodes and/or rejection.