Mucosal Perfusion Research Articles

Battle of the Gases: How Air and Nitrous Oxide Affect Endotracheal Tube Cuff Pressure During General Anesthesia.

Background Endotracheal tube (ETT) cuff pressure changes during general anesthesia. Endotracheal cuff pressure ideally should be maintained between 20 and 30 cm of H2O. Cuff pressure of less than 25 cm of H2O increases the chances of aspiration while pressure of more than 40 cm of H2O causes tracheal mucosa damage. The study aimed to monitor and compare variations of endotracheal cuff pressure during general anesthesia with oxygen-air or oxygen-nitrous oxide. Methods This prospective, randomized, double-blinded, observational study was conducted on 40 patients. After approval from the institutional ethics subcommittee, 40 patients of either gender, aged 18-60 years, belonging to ASA grades I and II, who were undergoing elective surgery under general anesthesia, were enrolled in this study. The patients were randomly divided into two groups, with 20 in each group. In Group A, oxygen-air and Group N, oxygen-nitrous oxide was used as a gaseous mixture in general anesthesia with ETT. The ETT cuff pressure was recorded with the help of a cuff manometer at intervals of five, 10, 20, 30, 40, 50, 60, 70, 80, and 90 minutes after intubation. If pressure was more than 40 cm of H2O, it was reduced to 25-30 cm of H2O. Data were collected and analyzed using methods described in Primer of Biostatistics by Stanton A. Glantz. Quantitative data were analyzed using the Student's t-test. Qualitative data were analyzed using the chi-square test. Results An increase in cuff pressure was noted more in Group N as compared to Group A. The pressure in the endotracheal cuff started to gradually increase after 30-40 minutes in Group N after intubation, while in Group A, there was no significant increase. The average number of times the cuff deflated was 0.2 ± 0.41 in Group A and 1.55 ± 0.51 in Group N, which was highly significant. Conclusion Changes in endotracheal cuff pressure were observed when using different gas mixtures for inflation. Specifically, cuff pressure increased with oxygen and nitrous oxide compared to oxygen with air. This suggests that anesthetic gas composition can impact cuff pressure, potentially affecting tracheal mucosal perfusion and patient safety. Therefore, regular monitoring and adjustment of cuff pressure is crucial, especially when using nitrous oxide, to prevent complications and ensure optimal patient care.

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.

Efficacy of a somatostatin analogue in a case of obscure gastrointestinal bleeding

Gastrointestinal bleeding can have many reasons and therapy becomes tricky when the diagnostic workout is not conclusive. We describe the case of an 89 y.o. woman with severe anemia and gastrointestinal bleeding of an unknown origin after conventional imaging and endoscopic procedures, thus averting endoscopic, angiographic or surgical approach. This condition required 39 blood transfusions in 2 months. Subcutaneous Octreotide, reducing gastrointestinal mucosal perfusion, achieved hemodynamic stability, improved blood cell count, and ended the blood transfusions. The use of somatostatin analogues can be considered in refractory patients with digestive bleedings of an unknown origin not susceptible of first line therapy.

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.

Subtotal Colectomy with Ileostomy, Surgical Management of Ischemic Colitis: A Case Study

Ischemic colitis (IC) occurs when blood flow to part of the colon is temporarily reduced. Most patients with IC usually have some associated comorbidities that affect mucosal perfusion. A long history of diabetes mellitus, vascular disease, atrial fibrillation, hypotension, and chronic kidney disease are comorbidities that need to be carefully considered in the diagnosis and management of the patient with IC. IC commonly manifests with a clinical trio of symptoms including abdominal pain, hematochezia, and diarrhea. Most cases are mild and self-limiting with a good prognosis, responding well to medical management including antibiotics and bowel rest; however, some dire situations may require surgical intervention. This case report will discuss clinical presentations, risk factors, diagnosis, and surgical treatment (subtotal colectomy with ileostomy) in a 50-year-old female patient with IC.

Evaluation of the endotracheal tube cuff pressure changes during cardiac operations under cardiopulmonary bypass.

Introduction: Tracheal intubation is used for most operations under general anesthesia. Prolonged hyperinflation of the tube cuff can compromise tracheal mucosal perfusion, and low pressure of the cuff may cause some other complications. The aim of this study was the evaluation of changes in intra-cuff pressure in patients undergoing cardiac surgeries under cardiopulmonary bypass. Methods: In an observational study 120 patient's candidate to cardiac operations under cardiopulmonary bypass were enrolled. After induction of anesthesia and tracheal intubation by same tracheal tubes, tracheal tube cuff pressure was adjusted to 20-25 mm Hg (T0). Then the cuff pressure was measured at beginning of CPB (Cardio Pulmonary Bypass) (T1), at 30º hypothermia (T2) and after separation from CPB (T3). Results: The mean cuff pressure was 33.5±7.3, 28.9±5.4, 25.6±5.2 and 28.1±3.7 at T0, T1, T2 and T3 respectively. Intra- cuff pressure changed significantly during cardiopulmonary bypass. Conclusion: The mean intra-cuff pressure was decreased during hypothermic cardiopulmonary bypass. The decrease in cuff pressure may protect the tracheal mucosa against hypotensive ischemic injury in these patients.

Comparison of gastric reactance with commonly used perfusion markers in a swine hypovolemic shock model

BackgroundThe gut has been hypothesized to be a protagonist tissue in multiple organ dysfunction syndrome (MODS) for the past three decades. Gastric reactance (XL) is a potential perfusion marker derived from gastric impedance spectroscopy (GIS), which is an emerging tool through which living tissue can be continuously measured to determine its pathophysiological evolution. This study aimed to compare the performance of XL [positive predictive values (PPV), negative predictive values (NPV), and area under the curve (AUC)] against commonly used perfusion markers before and during hypovolemic shock in swine subjects.MethodsProspective, controlled animal trial with two groups, control group (CG) N = 5 and shock (MAP ≤ 48 mmHg) group (SG) N = 16. Comparison time points were defined as T-2 (2 h before shock), T-1 (1 h before shock), T0 (shock), T1 (1 h after shock), and T2 (2 h after shock). Shock severity was assessed through blood gases, systemic and hemodynamic variables, and via histological examination for assessing inflammation-edema and detachment in the gastric mucosa. Macroscopic assessment of the gastric mucosa was defined in five levels (0—normal mucosa, 1—stippling or epithelial hemorrhage, 2—pale mucosa, 3—violet mucosa, and 4—marmoreal mucosa). Receiver Operating Characteristic (ROC) curves of perfusion markers and XL were calculated to identify optimal cutoff values and their individual ability to predict hypovolemic shock.ResultsComparison among the CG and the SG showed statistically significant differences in XL measurements at T-1, T0, T1, and T2, while lactate showed statistically significant differences until T1 and T2. Statistically significant differences were detected in mucosa class (p < 0.001) and in inflammation-edema in the gastric body and the fundus (p = 0.021 and p = 0.043). The performance of the minimum XL value per subject per event (XL_Min) was better (0.81 ≤ AUC ≤ 0.96, 0.93 ≤ PPV ≤ 1.00, 0.45 ≤ NPV ≤ 0.83) than maximum lactate value (Lac_Max) per subject per event (0.29 ≤ AUC ≤ 0.82, 0.82 ≤ PPV ≤ 0.91, 0.24 ≤ NPV ≤ 0.82). Cutoff values for XL_Min show progressive increases at each time point, while cutoff values for Lac_Max increase only at T2.ConclusionsXL proved to be an indirect and consistent marker of inadequate gastric mucosal perfusion, which shows significant and detectable changes before commonly used markers of global perfusion under the hypovolemic shock conditions outlined in this work.

A Comparative Study of Cuff Pressure Changes of Endotracheal Tube with the Use of Air Versus Nitrous Oxide in the Anaesthetic Gas Mixture During Laparoscopic Surgery.

Objective:Cuffed endotracheal tube remains the standard of care during laparoscopic surgeries. Nitrous oxide is widely used as a carrier gas in anaesthesia practice. Cuff pressure greater than 30 cm H2O impairs tracheal mucosal perfusion leading to necrosis. This study aimed to compare the endotracheal tube cuff pressure while using air versus nitrous oxide in the anaesthetic gas mixture during laparoscopic surgeries.Methods:Sixty patients aged 18-70 years undergoing laparoscopic surgery were randomized into 2 groups of 30 each. Group 1 patients received air and oxygen in the anaesthetic gas mixture and group 2 patients received nitrous oxide and oxygen. Cuff pressure changes were measured throughout the surgery and perioperative hemodynamic parameters were recorded. The incidence and severity of postoperative sore throat were also evaluated postoperatively for 24 hours.Results:The increase in cuff pressure was more in the group using nitrous oxide (40.80 ± 8.78 cm H2O) when compared to the group using air (26.93 ± 2.69 cm H2O) (P < .001). Trendelenburg position was associated with a significant increase in cuff pressure when compared to other positions. The incidence and severity of postoperative sore throat were more at 2 hours (P = .0099) and 4 hours (P = .0105) postoperatively in the group using nitrous oxide. The hemodynamic parameters were comparable between the 2 groups.Conclusion:The use of nitrous oxide in the anaesthetic gas mixture causes an increase in endotracheal tube cuff pressure and increased severity of postoperative sore throat during laparoscopic surgeries.

Poreklo ćelija enteričkog nervnog sistema i putevi migracije tokom embrionalnog razvoja

The enteric nervous system (ENS) is represented by a complex network of neurons, glial and other cells within the wall of the digestive tract. ENS is responsible for numerous, vital functions in our body. Thus, ENS regulates motility of the digestive tract, secretion into the intestinal lumen, exchange of fluid and electrolytes through the mucosa, as well as mucosal perfusion. In order to perform these important functions, proper embryonic development of ENS is necessary. ENS cells are derived from precursor cells of the neural crest (NCCs - neural crest cells). Two cell populations that contribute to the largest number of future ENS cells are the vagal and sacral NCCs. Vagal NCCs enter the primitive gut tube in the region of the future esophagus (foregut), and begin their migration, through the midgut towards the hindgut and the future anal region. Sacral NCCs enter the hindgut region following the extrinsic nerve fibers and continue their migration rostrally, towards vagal NCCs. Along with the migration process, these cells undergo other important processes, such as proliferation, neuro-glial differentiation, gangliogenesis, axonal pathway formation and synaptogenesis. All these processes are strictly regulated by numerous signaling pathways, which are still being actively researched. Modern lineage tracing and other technologies, that enabled following of individual precursor cells through their development pathways, will significantly contribute to the better understanding of development of ENS. This may have repercussions in improving the diagnosis and treatment of some developmental (Hirschsprung disease) and other ENS disorders.

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.

Schmallenberg virus infection suspected in a calf born to an imported heifer.

Schmallenberg virus infection suspected in a calf born to an imported heifer.

Comparison of Fissurectomy and Lateral Internal Sphincterotomy in the Surgical Management of Chronic Anal Fissure

Background: The anal fissure is a small spilt in the distal anoderm, and it most commonly occurs in the posterior midline of anal canal. Anal fissure causes severe sharp pain on defecation, occasionally accompanied by streak of blood on outside of stool or blood on toilet tissue. Fissures are classified as acute or chronic, acute fissure usually heal spontaneously within six weeks. Fissurectomy had been used as separate technique in the treatment of chronic anal fissure with favorable result. Parallel inside sphincterotomy produces an enduring fall of anal resting pressure, that reestablish mucosal perfusion bringing about recuperating, yet genuine drive component is obscure, and the instrument that travel from intense to constant gap stay dark. This study is design to assess the outcome between two groups, than better modality of the two could be chosen.&#x0D; Objective: To compare fissurectomy and lateral internal sphincterotomy in the management of chronic anal fissure.&#x0D; Patient and Methods: The Randomized controlled trial was conducted during 18-02-2015 to 17-08-2015 at Department of surgery,Liaquat University of Medical &amp; Health Sciences, Hyderabad. A total of 218 patients with chronic anal fissure were included in this study. Patients were randomly divided into two groups. Patients in Group A were underwent fissurectomy and patients group B was underwent lateral internal sphincterotomy. Surgery was performed and patients were followed for 8 weeks on regular basis and satisfactory out comes was noted. Information along with demographics was entered in the proforma.&#x0D; Results: Rate of satisfactory outcome was significantly high in group B as compare to group A [92.66% vs. 76.15%; p=0.001].&#x0D; Conclusion: Subcutaneous sidelong internal sphincterotomy is a significant surgery for patients with persistent anal fissure. It is compelling and safe, offers fast help of torment, and advances early gap mending without being gone to by any significant complexities.

Relationship between Gastric Blood Perfusion and Gastric Mucosal Injury Induced by Acute Cerebrovascular Disease in Rats

This study aims to discuss the relationship between gastric perfusion and gastric mucosal injury induced by acute cerebrovascular disease in rats. Healthy adult male Wistar rats weighing 280-320 g are randomly divided into the following 4 groups: middle cerebral artery occlusion-reperfusion group, middle cerebral artery occlusion -sham group, gastric ischemia-reperfusion group and gastric ischemia-sham group, with 12 in each group. In gastric ischemia-reperfusion group, the similar changes occur to the mucous membrane of the rats, such as hyperaemia, edema, spotty or patchy hemorrhage and partial mucous exfoliation. There is no significant difference between middle cerebral artery occlusion-reperfusion group and gastric ischemia-reperfusion group in the number of gastrin cells and the expression of gas, but the number of gastrin cells and the expression of gas are significantly higher than those of their corresponding sham operation group, resulting in statistically significant difference. The gastric mucosal blood flow is significantly increased in the middle and high dose groups, which has significant difference compared with normal saline group (p<0.05). One of the important mechanisms of Calcitonin gene-related peptide protecting ischemic gastric mucosal injury is to increase gastric mucosal blood perfusion and improve microcirculation.

Nutrient-induced hyperosmosis evokes vasorelaxation via TRPV1 channel-mediated, endothelium-dependent, hyperpolarisation in healthy and colitis mice.

In humans, blood flow in the mesenteric circulation is greatly increased after meals, but the mechanisms underlying postprandial mesenteric vasorelaxation induced by nutrients and whether this process is involved in the pathogenesis of colitis, are not well understood. Here we have studied the direct actions of nutrients on mesenteric arterial tone and the underlying molecular mechanisms in healthy and colitis mice. Colitis in C57BL/6 mice was induced with dextran sodium sulphate. Nutrient-induced vasorelaxation of mesenteric arterioles from humans and mice was studied with wire myograph assays. Ca2+ and Na+ imaging were performed in human vascular endothelial cells and vascular smooth muscle cells, using selective pharmacological agents and shRNA knockdown of TRPV1 channels. Glucose, sodium and mannitol concentration-dependently induced endothelium-dependent relaxation of human and mouse mesenteric arterioles via hyperosmotic action,. Hyperosmosis-induced vasorelaxation was almost abolished by selective blockers for TRPV1, IKCa and SKCa channels. Glucose markedly stimulated Ca2+ influx through endothelial TRPV1 channels, an effect attenuated by selective blockers and shRNA knockdown of TRPV1 channels. Capsaicin synergised the glucose-induced vasorelaxation. Nutrient-induced hyperosmosis also activated Na+ /K+ -ATPase and the Na/Ca exchanger (NCX) to decrease [Ca2+ ]i in VSMCs. Glucose-induced vasorelaxation was impaired in mouse colitis. Nutrient-induced hyperosmosis evoked endothelium-dependent mesenteric vasorelaxation via the TRPV1/Ca2+ / endothelium-dependent hyperpolarisation pathway to increase normal mucosal perfusion, which is impaired in our model of colitis. The TRPV1/Ca2+ / endothelium-dependent hyperpolarisation pathway could provide novel drug targets for gastrointestinal diseases with hypoperfusion, such as chronic colitis and mesenteric ischaemia.

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.

Quantitative serosal and mucosal optical imaging perfusion assessment in gastric conduits for esophageal surgery: an experimental study in enhanced reality

Introduction/objectiveGastric conduit (GC) is used for reconstruction after esophagectomy. Anastomotic leakage (AL) incidence remains high, given the extensive disruption of the gastric circulation. Currently, there is no reliable method to intraoperatively quantify gastric perfusion. Hyperspectral imaging (HSI) has shown its potential to quantify serosal StO2. Confocal laser endomicroscopy (CLE) allows for automatic mucosal microcirculation quantification as functional capillary density area (FCD-A). The aim of this study was to quantify serosal and mucosal GC’s microperfusion using HSI and CLE. Local capillary lactate (LCL) served as biomarker.MethodsGC was formed in 5 pigs and serosal StO2% was quantified at 3 regions of interest (ROI) using HSI: fundus (ROI-F), greater curvature (ROI-C), and pylorus (ROI-P). After intravenous injection of sodium-fluorescein (0.5 g), CLE-based mucosal microperfusion was assessed at the corresponding ROIs, and LCLs were quantified via a lactate analyzer.ResultsStO2 and FCD-A at ROI-F (41 ± 10.6%, 3.3 ± 3.8, respectively) were significantly lower than ROI-C (68.2 ± 6.7%, p value: 0.005; 18.4 ± 7, p value: 0.01, respectively) and ROI-P (72 ± 10.4%, p value: 0.005; 15.7 ± 3.2 p value: 0.001). LCL value at ROI-F (9.6 ± 4.7 mmol/L) was significantly higher than at ROI-C (2.6 ± 1.2 mmol/L, p value: 0.04) and ROI-P (2.6 ± 1.3 mmol/L, p value: 0.04). No statistically significant difference was found in all metrics between ROI-C and ROI-P. StO2 correlated with FCD-A (Pearson’s r = 0.67). The LCL correlated negatively with both FCD-A (Spearman’s r = − 0.74) and StO2 (Spearman’s r = − 0.54).ConclusionsGC formation causes a drop in serosal and mucosal fundic perfusion. HSI and CLE correlate well and might become useful intraoperative tools.

A new photoplethysmographic device for continuous assessment of urethral mucosa perfusion: evaluation in a porcine model.

This study proposes to evaluate an innovative device consisting of an indwelling urinary catheter equipped with a photoplethysmography (PPG) sensor in contact with the urethral mucosa that provides a continuous index called urethral perfusion index (uPI). The goal of this study was to determine if the uPI could bring out tissue perfusion modifications induced by hypotension and vasopressors in a porcine model. Twelve piglets were equipped for heart rate, MAP, cardiac index, stroke volume index, systemic vascular resistance index and uPI monitoring. The animals were exposed to different levels of mean arterial pressure (MAP), ranging from low to high values. Friedman tests with a posteriori multiple comparison were performed and a generalized linear mixed model (GLMM) was used to assess the relationship between uPI and MAP. Urethral Perfusion Index and other haemodynamic parameters varied significantly at the different time-points of interest. There was a positive correlation between MAP and uPI below a specific MAP value, called dissociation threshold (DT). Above this threshold, uPI and MAP were negatively correlated. This relationship, assessed with the GLMM, yielded a significant positive fixed effect coefficient (+ 0.2, P < 0.00001) below the DT and a significant negative fixed effect (- 0.14, P < 0.00001) above DT. In an experimental setting, the PPG device and its index uPI permitted the detection of urethral mucosa perfusion alterations associated with hypotension or excessive doses of vasopressors. Further studies are needed to evaluate this device in a clinical context.

Selepressin, a novel selective V1A receptor agonist: Effect on mesenteric flow and gastric mucosa perfusion in the endotoxemic rabbit

Intestinal or mesenteric ischemia generally leads to inflammation and injury, potentially developing hypoxia, causing cell death and tissue necrosis. This in turn can lead to sepsis and shock. Conversely, following shock, the intestinal tract is a main organ to experience ischemic/reperfusion injury. Increased intestinal cell-membrane permeability through mesenteric ischemia provoking bacterial translocation and gut-barrier injury can lead to sepsis and multi-organ failure. Hypotension induced by systemic vasodilation and vascular leak in systemic inflammatory response syndrome and sepsis is countered by immediate fluid resuscitation and vasopressor administration, primarily norepinephrine (NE), with possible arginine vasopressin (AVP) supplementation, an agonist of vasopressin V1A and V2 receptors. Selepressin is a selective V1A-receptor agonist, avoiding potential V2 receptor-associated adverse effects. Selepressin, non-selective AVP, and NE effects on mesenteric blood flow (MBF) and gastric mucosa perfusion (GMP) were compared in control rabbits and a lipopolysaccharide-induced, fluid-resuscitated rabbit endotoxemia model. AVP induced a pronounced decrease in MBF and GMP in non-endotoxemic and endotoxemic rabbits, whereas the reduction after selepressin treatment was significantly less for both indicators in the endotoxemic animals. By contrast, NE increased the MBF and did not affect GMP in both groups. Selepressin and AVP induced a pronounced dose-dependent increase in mesenteric vascular resistance in non-endotoxemic and endotoxemic rabbits, tending to be less in endotoxemic animals, whereas a minor increase in both groups was observed with NE. Therefore, in this safety study, the risk for mesenteric ischemia on selepressin treatment was not inferior to AVP, being less in endotoxemic than in non-endotoxemic animals.

Simultaneous computer-assisted assessment of mucosal and serosal perfusion in a model of segmental colonic ischemia.

Fluorescence-based enhanced reality (FLER) enables the quantification of fluorescence signal dynamics, which can be superimposed onto real-time laparoscopic images by using a virtual perfusion cartogram. The current practice of perfusion assessment relies on visualizing the bowel serosa. The aim of this experimental study was to quantify potential differences in mucosal and serosal perfusion levels in an ischemic colon segment. An ischemic colon segment was created in 12 pigs. Simultaneous quantitative mucosal and serosal fluorescence imaging was obtained via intravenous indocyanine green injection (0.2mg/kg), using two near-infrared camera systems, and computer-assisted FLER analysis. Lactate levels were measured in capillary blood of the colonic wall at seven regions of interest (ROIs) as determined with FLER perfusion cartography: the ischemic zone (I), the proximal and distal vascularized areas (PV, DV), and the 50% perfusion threshold proximally and distally at the mucosal and serosal side (P50M, P50S, D50M, D50S). The mean ischemic zone as measured (mm) for the mucosal side was significantly larger than the serosal one (56.3 ± 21.3 vs. 40.8 ± 14.9, p = 0.001) with significantly lower lactate values at the mucosal ROIs. There was a significant weak inverse correlation between lactate and slope values for the defined ROIs (r = -0.2452, p = 0.0246). Mucosal ischemic zones were larger than serosal zones. These results suggest that an assessment of bowel perfusion from the serosal side only can underestimate the extent of ischemia. Further studies are required to predict the optimal resection margin and anastomotic site.

A randomized-controlled trial of arginine infusion in severe sepsis on microcirculation and metabolism.

Sepsis is hypothesized as an arginine deficient state, with lack of nitric oxide (NO) for adequate microcirculation and local perfusion. This study aimed to investigate if prolonged (72-h) intravenous l-arginine administration in sepsis patients improves microcirculation. Secondly, effects on arginine and protein metabolism, and organ function were studied. Critically ill patients with a diagnosis of septic shock participated in a long-term (72h) randomized double-blind placebo-controlled parallel-group study. l-arginine-HCl (1.2μmolkg-1min-1; n=9) or l-alanine (isocaloric control: 2.4μmolkg-1min-1; n=9) was continuously infused. Primary study outcome was microcirculation, assessed as gastric mucosal perfusion by gastric tonometry (Pr-aCO2 gap) and skin perfusion by Laser Doppler flowmetry. Secondary endpoints were whole body (WB) arginine and protein metabolism, organ function and clinical outcomes. We measured global hemodynamics continuously for safety monitoring. Statistical analyses were performed by mixed model for repeated measures with treatment by time interaction as estimate for between-group difference. Pr-aCO2 increased only in the l-arginine group (p=0.006), without a significant between-group difference (p=0.17). We found no significant differences in skin perfusion parameters. l-arginine infusion resulted in a larger increase of plasma arginine and ornithine concentrations (p<0.01), WB (endogenous) arginine appearance (p<0.001), WB NO synthesis (p=0.027) and WB arginine to urea conversion (p<0.001) than infusion of l-alanine. We found no effect on global hemodynamics, and protein metabolism by l-arginine infusion. Organ function parameters were unaffected, except for a significant difference between groups in intra-abdominal pressure over time (p=0.029). Prolonged intravenous l-arginine administration does not improve local perfusion and organ function despite an increase in WB NO synthesis. Administration is safe with regard to global hemodynamics, but the observed increase in Pr-aCO2 and intra-abdominal pressure warrants careful application of l-arginine infusion and further research, especially in the early stage of septic shock.