Normal Tissue Perfusion Research Articles

Abstract 2056: Impaired Cellular Metabolic Adaptations In Autosomal-Dominant Hyper-IgE Syndrome: Possible Implications To Deficient Angiogenesis And Wound Healing

Background: Autosomal dominant Hyper-IgE syndrome (AD-HIES; Job’s syndrome) is caused by dominant negative mutations in signal transducer and activator of transcription 3 (STAT3). Patients present with immunodeficiency accompanied by severe non-immunological features including poor post infection lung healing, subsequent pulmonary failure, and skeletal, connective tissue, and vascular abnormalities including arterial tortuosity and aneurisms which can lead to myocardial infarction and subarachnoid hemorrhage. HIF1a-dependent deficient angiogenesis has been implicated in the abnormal wound healing response of AD-HIES. Both STAT3 and HIF1a are major regulators of cellular metabolism. In this study we are testing the hypothesis that dysregulation of cellular metabolic pathways may contribute to AD-HIES pathophysiology. Methods: We used skin fibroblasts (SF) from 4 AD-HIES patients and 4 normal volunteers. To investigate ability of the cells to adapt and function in nutrient-deficient conditions (to model tissue damages disrupting normal tissue perfusion) we exposed them to a culture media lacking glucose, pyruvate and glutamine (deficient media). We used a live imaging approach (IncucyteS3 System, Sartorius) to analyze cell proliferation, reactive oxygen species (ROS), cell death, and wound closing ability (scratch-wound assay). Results: In deficient media, both AD-HIES and control SF decreased their proliferation rate. While control SF adapted, AD-HIES SF showed decreased survival after prolong nutrient deprivation. Level of ROS, measured at 12, 24, 48h in deficient media was 25% higher in AD-HIES SF (n=8, P=0.003). We used a scratch-wound assay to assess the ability of fibroblasts to migrate and close the wound after 48h of adaptation to deficient media. In full media, both control and AD-HIES fibroblast completely closed the wound within 36h. In deficient media, wound closure was delayed to much higher degree by AD-HIES fibroblasts (60±14% closure by control SF vs 18±9% by AD-HIES SF, n=4, P=0.016). Conclusions: Adaptive remodeling of cellular metabolism is impaired in AD-HIES SF that may contribute to deficient angiogenesis and poor wound healing, suggesting possible therapeutic targets within cellular metabolic pathways.

Goal-directed fluid therapy guided by plethysmographic variability index versus conventional liberal fluid therapy in neonates undergoing abdominal surgery: A prospective randomized controlled trial.

Intraoperative fluid therapy maintains normovolemia, normal tissue perfusion, normal metabolic function, normal electrolytes, and acid-base status. Plethysmographic variability index has been shown to predict fluid responsiveness but its role in guiding intraoperative fluid therapy is still elusive. The aim of the present study was to compare intraoperative goal-directed fluid therapy based on plethysmographic variability index with liberal fluid therapy in term neonates undergoing abdominal surgeries. A prospective randomized controlled study was conducted in a tertiary care centre, over a period of 18 months. A total of 30 neonates completed the study out of 132 neonates screened. Neonates with tracheoesophageal fistula, congenital diaphragmatic hernia, congenital heart disease, respiratory disorders, creatinine clearance <90 mL/min and who were hemodynamically unstable were excluded. Neonates were randomized to goal-directed fluid therapy group where the plethysmographic variability index was targeted at <18 or liberal fluid therapy group. Primary outcome was comparison of total amount of fluid infused intraoperatively in both the groups. Secondary outcomes included intraoperative and postoperative arterial blood gas parameters, biochemical parameters, use of vasopressors, number of fluid boluses, complications and duration of hospital stay. There was no significant difference in total intraoperative fluid infused [90 (84-117.5 mL) in goal-directed fluid therapy and 105 (85.5-144.5 mL) in liberal fluid therapy group (p = .406)], median difference (95% CI) -15 (-49.1 to 19.1). There was a decrease in serum lactate levels in both groups from preoperative to postoperative 24 h. The amount of fluid infused before dopamine administration was significantly higher in liberal fluid therapy group (58 [50.25-65 mL]) compared to goal-directed fluid therapy group (36 [22-44 mL], p = .008), median difference (95% CI) -22 (-46 to 2). In postoperative period, the total amount of fluid intake over 24 h was comparable in two groups (222 [204-253 mL] in goal-directed fluid therapy group and 224 [179.5-289.5 mL] in liberal fluid therapy group, p = .917) median difference (95% CI) cutoff -2 (-65.3 to 61.2). Intraoperative plethysmographic variability index-guided goal-directed fluid therapy was comparable to liberal fluid therapy in terms of total volume of fluid infused in neonates during perioperative period. More randomized controlled trials with higher sample size are required. Central Trial Registry of India (CTRI/2020/02/023561).

Mechanisms of Physiological Angiogenesis

Angiogenesis is the formation of blood vessels from existing vasculature to provide n-ormal tissue perfusion. Angiogenesis is also necessary for the processes of growth and regeneration. Angiogenesis attracts the attention of researchers from the position of its therapeutic regulation: enhancement can contribute to significant progress in the treatment of ischemic diseases, and inhibition is actively studied for the treatment of neoplastic diseases. Regulation of angiogenesis is impossible without accurate knowledge of its mechanism. There are two fundamental pathways for angiogenesis: sprouting angiogenesis, which is mediated by an existing vessel’s endothelial cells migration into the extracellular matrix to form a vessel in the direction of angiogenic stimuli, and intussusceptive angiogenesis, which is mediated by dividing the formed vessel into two new ones as a re-sult of the formation of a partition inside it that separates two independent lumens. This review examines the main stages of each type of physiological angiogenesis, their mechanisms and regulation.

Correlation Between Mean Arterial Pressure and Capillary Refill Time in Patients with Septic Shock: A Systematic Review and Meta-analysis.

Background: The initial hemodynamic goal during septic shock resuscitation is to achieve a mean arterial pressure (MAP) above 65 mm Hg, although this does not assure a normal tissue perfusion. Capillary refill time (CRT), a marker of skin blood flow, has been validated as a marker of the reperfusion process. The aim of the study was to explore the relationship between MAP and CRT in patients in septic shock. Methods: We systematically reviewed studies which reported CRT and MAP in septic shock patients. Authors of eligible studies were asked to provide necessary data for performing a meta-correlation of Spearman's rank correlation coefficients. Subgroup analyses were performed, including studies of good quality and studies with higher/lower norepinephrine doses. Results: We identified 10 studies, comprising 917 patients. There were 5 studies considered to be of good quality. A meta-correlation showed a statistically significant but poor negative correlation between MAP and CRT (R = -0.158, range -0.221 to -0.093, P < .001, I2 = 0.0%). Subgroup analysis of best-quality studies gave similar results (R = -0.201, range -0.282 to -0.116, P < .001, I2 = 0.0%). In subanalysis concerning norepinephrine doses, no significant correlations were found. Conclusions: In patients with septic shock, there is poor inverse correlation between MAP and CRT. MAP > 65 mm Hg does not guarantee normalization of CRT.Registration code: PROSPERO: CRD42022355996. Registered on 5 September 2022.

Unchanged perfusion in normal-appearing white and grey matter of glioma patients nine months after proton beam irradiation

Purpose Radio(chemo)therapy is used as a standard treatment for glioma patients. The surrounding normal tissue is inevitably affected by the irradiation. The aim of this longitudinal study was to investigate perfusion alterations in the normal-appearing tissue after proton irradiation and assess the dose sensitivity of the normal tissue perfusion. Methods In 14 glioma patients, a sub-cohort of a prospective clinical trial (NCT02824731), perfusion changes in normal-appearing white matter (WM), grey matter (GM) and subcortical GM structures, i.e. caudate nucleus, hippocampus, amygdala, putamen, pallidum and thalamus, were evaluated before treatment and at three-monthly intervals after proton beam irradiation. The relative cerebral blood volume (rCBV) was assessed with dynamic susceptibility contrast MRI and analysed as the percentage ratio between follow-up and baseline image (ΔrCBV). Radiation-induced alterations were evaluated using Wilcoxon signed rank test. Dose and time correlations were investigated with univariate and multivariate linear regression models. Results No significant ΔrCBV changes were found in any normal-appearing WM and GM region after proton beam irradiation. A positive correlation with radiation dose was observed in the multivariate regression model applied to the combined ΔrCBV values of low (1–20 Gy), intermediate (21–40 Gy) and high (41–60 Gy) dose regions of GM (p < 0.001), while no time dependency was detected in any normal-appearing area. Conclusion The perfusion in normal-appearing brain tissue remained unaltered after proton beam therapy. In further studies, a direct comparison with changes after photon therapy is recommended to confirm the different effect of proton therapy on the normal-appearing tissue.

A Multimodality Myocardial Perfusion Phantom: Initial Quantitative Imaging Results.

This proof-of-concept study explores the multimodal application of a dedicated cardiac flow phantom for ground truth contrast measurements in dynamic myocardial perfusion imaging with CT, PET/CT, and MRI. A 3D-printed cardiac flow phantom and flow circuit mimics the shape of the left ventricular cavity (LVC) and three myocardial regions. The regions are filled with tissue-mimicking materials and the flow circuit regulates and measures contrast flow through LVC and myocardial regions. Normal tissue perfusion and perfusion deficits were simulated. Phantom measurements in PET/CT, CT, and MRI were evaluated with clinically used hardware and software. The reference arterial input flow was 4.0 L/min and myocardial flow 80 mL/min, corresponding to myocardial blood flow (MBF) of 1.6 mL/g/min. The phantom demonstrated successful completion of all processes involved in quantitative, multimodal myocardial perfusion imaging (MPI) applications. Contrast kinetics in time intensity curves were in line with expectations for a mimicked perfusion deficit (38 s vs. 32 s in normal tissue). Derived MBF in PET/CT and CT led to under- and overestimation of reference flow of 0.9 mL/g/min and 4.5 mL/g/min, respectively. Simulated perfusion deficit (0.8 mL/g/min) in CT resulted in MBF of 2.8 mL/g/min. We successfully performed initial, quantitative perfusion measurements with a dedicated phantom setup utilizing clinical hardware and software. These results showcase the multimodal phantom’s potential.

Evaluation of coccygeal and radial artery Doppler blood pressure measurements in sick cats with and without abnormalities in tissue perfusion.

To compare systolic blood pressure measured by Doppler (SBP) taken from the coccygeal artery versus common digital branch of the radial artery in cats with normal and poor perfusion parameters. Prospective, observational study. University Teaching Hospital. Eighty-five cats presenting to the emergency service for which prior emergency treatment was not received and a blood pressure was indicated on triage. Systolic blood pressure was measured by Doppler using the radial and coccygeal arteries. Cats were categorized as having normal or poor tissue perfusion based on physical examination. Agreement was poor between coccygeal and radial SBP overall with absolute and relative bias (95% limits of agreement) of 23 (-51 to 96) mm Hg and 16% (-38% to 69%), respectively. In cats with poor perfusion, the agreement was absolute bias=28mm Hg and relative bias=22% and with normal perfusion absolute bias=22mm Hg, and relative bias=12%. The median (interquartile range) coccygeal SBP was significantly different from the radial SBP 141 (50) mm Hg versus 120 (45) mm Hg, P<0.001. In multivariate linear regression, heart rate was negatively associated with coccygeal SBP (r2 =0.088, P=0.049), and pale mucous membrane color (P=0.034) and poor pulse quality (P=0.007) were independently associated with lower radial SBP (r2 =0.18). Median coccygeal SBP is significantly greater than radial SBP in sick cats with both normal perfusion and hypoperfusion. Agreement between coccygeal and radial SBP is poor in cats and cannot be used interchangeably. As clinically significant differences exist between sites, the authors recommend obtaining SBP from both sites initially and choosing to monitor and trend changes with the one site that correlates most with physical examination findings.

Abstract No. 48 Usefulness of cone-beam computed tomography during bronchial artery embolization

Bronchial artery embolization (BAE) is a well-established intervention for treating benign and malignant causes of hemoptysis with high success rate from 70-99%; a subset of these procedures involve bronchial artery chemoperfusion, which has been used in palliation of lung malignancies. One of the dreaded complications of BAE is non-target embolization resulting in spinal cord ischemia, occurring in 0.6-4.4% of patients. This study aims to examine whether the adjunct use of CBCT with digital subtraction angiography (DSA) has an impact on BAE interventions. Twenty-one (10M, 11F) patients of mean age 55.5 who underwent DSA with CBCT prior to BAE from 2010 to 2020 were evaluated for single-institutional retrospective study. Retrospective analysis of the dictated reports were performed in conjunction with the available stored images and findings were summarized into 3 categories: 1) CBCT added no benefit; 2) CBCT added benefit (i.e., increased diagnostic confidence) without change in procedural management; 3) CBCT added benefit with change in intraprocedural management. The frequency and percentage of each category were calculated. 14/21 patients (66.7%) (95% CI: 0.47-0.87) were placed into category 2 whereby CBCT increased diagnostic confidence for embolization. The remaining 7/21 (33.3%) patients (95% CI: 0.13-0.53) were placed into category 3. In 3 of these patients, CBCT resulted in microcatheter repositioning to a selective bronchial artery branch to avoid nontarget embolization of a spinal artery. In 2 patients, CBCT confirmed normal tissue perfusion resulting in microcatheter repositioning to find an alternate source. In the remaining 2 patients, CBCT showed additional intercostal collaterals to ipsilateral bronchial arteries, which were then embolized. No cases were placed into category 1. One patient (4.8%) had a complication of spinal cord ischemia likely related to non-target embolization via small posterior radiculomedullary arterial branches, which in retrospect were seen on CBCT but not DSA. No other complications were seen. Adjunct use of CBCT during BAE provides additional information beyond DSA. This resulted in increased diagnostic confidence 67% of the time and in 33% of cases resulted in intraprocedural change in management, often to avoid non-target embolization via DSA-occult spinal arteries.

Arterial Input Functions and Tissue Response Curves in Dynamic Glucose-Enhanced (DGE) Imaging: Comparison Between glucoCEST and Blood Glucose Sampling in Humans.

Dynamic glucose-enhanced (DGE) imaging uses chemical exchange saturation transfer magnetic resonance imaging to retrieve information about the microcirculation using infusion of a natural sugar (D-glucose). However, this new approach is not yet well understood with respect to the dynamic tissue response. DGE time curves for arteries, normal brain tissue, and cerebrospinal fluid (CSF) were analyzed in healthy volunteers and compared with the time dependence of sampled venous plasma blood glucose levels. The arterial response curves (arterial input function [AIF]) compared reasonably well in shape with the time curves of the sampled glucose levels but could also differ substantially. The brain tissue response curves showed mainly negative responses with a peak intensity that was of the order of 10 times smaller than the AIF peak and a shape that was susceptible to both noise and partial volume effects with CSF, attributed to the low contrast-to-noise ratio. The CSF response curves showed a rather large and steady increase of the glucose uptake during the scan, due to the rapid uptake of D-glucose in CSF. Importantly, and contrary to gadolinium studies, the curves differed substantially among volunteers, which was interpreted to be caused by variations in insulin response. In conclusion, while AIFs and tissue response curves can be measured in DGE experiments, partial volume effects, low concentration of D-glucose in tissue, and osmolality effects between tissue and blood may prohibit quantification of normal tissue perfusion parameters. However, separation of tumor responses from normal tissue responses would most likely be feasible.

Laminin-dystroglycan signaling regulates retinal arteriogenesis.

Proper arteriovenous morphogenesis is crucial for maintaining normal tissue perfusion. However, our understanding of how arterial morphogenesis is regulated in the CNS is incomplete. In this study, we asked whether vascular basement membrane (BM) laminins, specifically the γ3-containing isoforms, regulate retinal arterial morphogenesis. We provide evidence that Laminin-γ3 is deposited at both arterial and venous BMs during arteriogenesis. Vascular BM Laminin-γ3 bound dystroglycan (DG), a laminin receptor preferentially expressed by arterial endothelial cells (ECs) during arteriogenesis. Blockade of laminin-DG binding in vitro led to decreased Delta-like ligand (DLL)-4 expression in ECs. Moreover, genetic deletion of the Laminin-γ3- and EC-specific deletion of DG led to similar defects in retinal arteriogenesis, including reduced Dll4 expression, hyperbranching and reduced smooth muscle coverage. These results implicate a newly identified Laminin-γ3-DG signaling cascade that regulates arterial Dll4/Notch signaling to specify and stabilize retinal arteries.-Biswas, S., Watters, J., Bachay, G., Varshney, S., Hunter, D. D., Hu, H., Brunken, W. J. Laminin-dystroglycan signaling regulates retinal arteriogenesis.

Hyperthermic intrathoracic chemotherapy after extended pleurectomy and decortication for malignant pleura mesothelioma: an observational study on outcome and microcirculatory changes.

In the treatment of malignant pleural mesothelioma the Hyperthermic Intra THOracic Chemotherapy (HITHOC) can improve the efficacy of pleurectomy and decortication with a local cytotoxic effect. However its biological impact in patient's hemodynamic and microcirculatory changes were rarely investigated. Aim of this study is to describe our experience with HITHOC after pleurectomy and decortication evaluating the role of sublingual video-microscopy in assessing the microcirculatory changes in the perioperative period. This is a prospective and observational study concerning 10 consecutive patients undergoing extended P/D followed by HITHOC. These patients underwent sublingual microcirculatory monitoring, which was adopted as a routine procedure since 2012. Haemodynamic parameters were collected at eight consecutive times: the day before surgery (T1), induction of anaesthesia (T2), surgical phase before HITHOC beginning (T3), 5 and 30 minutes after HITHOC start (T4 and T5, respectively), 5 minutes from HITHOC end (T6), after the admission in ICU (T7), at discharge from the ICU (T8). Cardiac output (CO) was calculated with MostCare. Systemic vascular resistance (SVR), oxygen delivery (DO2), and oxygen extraction rate (O2ER) were calculated using standard formulas. Arterial blood pressure and central venous pressure (CVP) were obtained with standard arterial and venous catheters. At the same times we assessed the sublingual microcirculation with Sidestream Dark Field technique. Hemodynamic and microcirculatory data were collected in 10 patients, 8 male and 2 females (mean age 68.6±9.0, and body surface area of 1.9±0.1 m2). All patients had arterial hypertension, and one patient had diabetes. The mean arterial pressure significantly decreased at T2, with respect to T1 (P=0.05). CO, CVP, DO2, O2ER, and ScvO2, did not change significantly over the time. All patients needed infusion of noradrenalin from T4 to T6. TVD significantly decreased from T1 to T3, T5, and T8. Similarly, PVD significantly decreased from T1 to T3 and T8, and MFI from T1 to T6 and T8. PPV and HI did not change over the study period. No correlation was found between hemodynamic parameters (MAP, CO, CVP, DO2, O2ER, ScvO2) and microcirculatory data (TVD, PVD, PPV, MFI, HI), at any time of the study. In patients who receive HITHOC the fluid load can reduce the microvascular impairment restoring the normal tissue perfusion. This process takes days but is most evident in the first 72 h. The use of colloid and blood transfusion is much more effective in restoring microcirculation and reducing tissue damaging.

Perioperative intravenous fluid therapy in children: guidelines from the Association of the Scientific Medical Societies in Germany.

This consensus- based S1 Guideline for perioperative infusion therapy in children is focused on safety and efficacy. The objective is to maintain or re-establish the child's normal physiological state (normovolemia, normal tissue perfusion, normal metabolic function, normal acid- base- electrolyte status). Therefore, the perioperative fasting times should be as short as possible to prevent patient discomfort, dehydration, and ketoacidosis. A physiologically composed balanced isotonic electrolyte solution (BS) with 1-2.5% glucose is recommended for the intraoperative background infusion to maintain normal glucose concentrations and to avoid hyponatremia, hyperchloremia, and lipolysis. Additional BS without glucose can be used in patients with circulatory instability until the desired effect is achieved. The additional use of colloids (albumin, gelatin, hydroxyethyl starch) is recommended to recover normovolemia and to avoid fluid overload when crystalloids alone are not sufficient and blood products are not indicated. Monitoring should be extended in cases with major surgery, and autotransfusion maneuvers should be performed to assess fluid responsiveness.

Same Heart and Different Sleep? A Brief Review of the Association between Sleep Apnea Syndrome and Heart Failure Based on Two Clinical Cases

The research in the field of sleep medicine has increased during the whole twentieth century, principally for the involvement of sleep-related disordered breathing (SDB) in cardiovascular disease. If sleep encompasses about a third of one’s life, the reasons are mostly linked to its effects on the cardiovascular and respiratory systems. Sleep is a physiological phenomenon characterized by changes in the human body leading to a state of quiescence of the cardiovascular, respiratory and metabolic systems [1]. The importance of these events becomes more evident if we Review Article British Journal of Medicine & Medical Research, 4(1): 34-45, 2014 35 consider what happens in their absence, that is, during SDB syndromes. These syndromes include habitual snoring, sleep apnea, Cheyne-Stokes breathing syndrome and sleep hypoventilation syndrome [2]. Sleep apnea syndromes are characterized by several apneic events during the night, which consist in absence of the airflow or its reduction by more than 90% lasting more than 10 seconds, with consequent oxyhemoglobin desaturation and arousal [2]. These events provoke microawakening and sleep fragmentation that represent, along with hypoxemia, important harmful triggers on the cardiovascular system. In fact, SDB presents as a highly prevalent comorbidity in patients with heart failure (HF); both diseases are related to each other in a bidirectional way through multiple mechanisms: apneic events raise cardiac afterload, and at the same time impaired cardiac function itself may contribute to the development of sleep apnea. HF is a clinical syndrome characterized by signs or symptoms due to the inability of the heart to provide a normal tissue perfusion: the failing cardiac pump is not able to maintain an adequate output for this task. Typical features of HF are represented by shortness of breath, resting or exertion dyspnea, fatigue, fluid retention leading to pulmonary congestion or ankle swelling, and objective evidence of a structurally or functionally abnormal heart at rest [1,3].

Intravenous contrast-enhanced sonography in children and adolescents - a single center experience.

Compared to adult patients, ultrasonography in children and adolescents is much more common, due to lack of ionizing radiation, and its wide availability. With the introduction of contrast-media for use in ultrasonography, one major drawback of the method could be overcome. In Europe, SonoVue® is the only widely available agent, which due to improved stability makes it possible to image normal and diseased tissue perfusion and vascularization with high accuracy. Inability to hold the breath and voluntary body movement of the patient is less of an obstacle compared to color Doppler techniques and makes the method very attractive for use in children, which, depending on age, may not be very cooperative. Use of intravenous contrast-medium in minors is currently very limited for several reasons: availability, lack of recommendation in national and international guidelines, and lack of official licensing. The article will touch medical indications, technique, safety considerations, and perspective of intravenous use of contrast-media in children and adolescents, including data from a 6-year period in 37 patients.PurposeThe purpose of the study was to collect data on ultrasonographic examinations, expanded by intravenous administration of the contrast agent SonoVue® in children and adolescents. Besides assessing diagnostic yield, data on adverse medication effects was collected.Materials and methodsThe study includes contrast-enhanced ultrasound examinations in 37 children at a single institution. Indications for the examinations were tumor lesions, infections, traumatic organ injuries, and parenchymal organ ischemia. Parents of the patients and adolescent patients were informed about the off-label use of the contrast agent. Thirty-nine examinations were performed, the average age of the patient was 11.1 years (range 1 to 17 years).ResultsAll of the examinations yielded additional diagnostic value, always expanding results from B mode and color coded sonography. Overall, most examinations were done to assess the liver (n=16), followed by the kidney in 10 cases. The different etiologies were encountered in the following order: tumor (n=22), infection (n=9), trauma (n=5), ischemia (n=4). Most examinations were performed to evaluate a hepatic lesion (n=12). There was one incident recorded that fit the criteria of a possible adverse effect. In an 8-year-old girl nausea was noted, that started 15 minutes after the end of the examination and resolved spontaneously. In none of the patients medical treatment for adverse effects was necessary.ConclusionUltrasonography in children, enhanced by intravenous use of contrast medium is feasible and allows for further evaluating cystic and solid tumors, and organ perfusion. Given that proper medical equipment and correct ultrasound machine settings are used, it is a robust method without diagnostic failures. In this small-sized case series there were no severe adverse effects, however, off-label use in children needs to be addressed.

Hyperglycemic Emergencies in Adults

Hyperglycemic Emergencies in Adults

Compromised regulation of tissue perfusion and arteriogenesis limit, in an AT1R-independent fashion, recovery of ischemic tissue in Cx40−/−mice

Recently, we reported that recovery of tissue perfusion in the ischemic hindlimb was reduced, inflammatory response increased, and survival of distal limb tissue compromised in connexin 40 (Cx40)-deficient (Cx40(-/-)) mice. Here we evaluate whether genotype-specific differences in tissue perfusion, native vascular density, arteriogenesis, blood pressure, and chronic ANG II type 1 receptor (AT1R) activation contribute to poor recovery of ischemic hindlimb tissue in Cx40(-/-) mice. Hindlimb ischemia was induced in wild-type (WT), Cx40(-/-), and losartan-treated Cx40(-/-) mice by using surgical procedures that either maintained (mild surgery) or compromised (severe surgery) perfusion of major collateral vessels supplying the distal limb. Pre- and postsurgical hindlimb perfusion was evaluated, and tissue survival, microvascular density, and macrophage infiltration were documented during recovery. Hindlimb perfusion was compromised in presurgical Cx40(-/-) versus WT mice despite comparable native microvascular density. Hindlimb perfusion 24 h postsurgery in Cx40(-/-) and WT mice was comparable after mild surgery (collateral vessels maintained), but compromised arteriogenesis in Cx40(-/-) animals nevertheless limited subsequent recovery of tissue perfusion and compromised tissue survival. Prolonged pre- and postsurgical treatment of Cx40(-/-) mice with losartan (an AT1R antagonist) normalized blood pressure but did not improve tissue perfusion or survival, despite reduced macrophage infiltration. Thus it appears Cx40 is necessary for normal tissue perfusion and for recovery of perfusion, arteriogenesis, and tissue survival in the ischemic hindlimb. Our data suggest that Cx40(-/-) mice are at significantly greater risk for poor recovery from ischemic insult due to compromised regulation of tissue perfusion, vascular remodeling, and prolonged inflammatory response.

Importance of Continuous Pulse Oximetry of the Ipsilateral Thumb/Index Finger during Transradial Angiography

We present a case of a 63-year-old male undergoing attempted basilar artery embolization using a right transradial artery approach in which continuous pulse oximetry of the ipsilateral thumb uncovered unanticipated hand ischemia during the procedure. A preprocedural evaluation using pulse oximetry of the right thumb demonstrated normal waveform and maintenance of normal oxygen saturation during manual compression of the right radial artery. This normal waveform and oxygen saturation was maintained after insertion of a 6Fr sheath into the radial artery. After insertion of a 6Fr guiding catheter into the right vertebral artery, near-complete dampening of the pulse oximetry waveform and precipitous decline in oxygen saturation were noted. Examination of the right hand demonstrated poor tissue perfusion. Immediate removal of the guiding catheter led to return of a normal waveform, oxygen saturation, and tissue perfusion. This case demonstrates the importance of continuous, intraprocedural monitoring of oxygenation of the ipsilateral hand during transradial angiography in order to avoid unanticipated perfusion abnormalities.

Dealing with liver trauma

Bleeding from a traumatic liver injury often ceases spontaneously, which is the basis for non-operative management, currently used in about 80% of patients with blunt hepatic trauma. The selection of patients for non-operative management is based on the assessment of haemodynamic stability and the presence of associated organ injuries requiring surgical repair. In patients requiring surgery, definitive repair is preferred in stable patients with normal tissue perfusion and temperature, and ranges from the use of local haemostats and sutures to non-anatomic hepatic resection and direct repair of juxtahepatic venous injuries. In the most seriously injured patients with major bleeding causing severe physiological derangement, a damage control strategy including perihepatic packing is the treatment method of choice. Adjunctive procedures including hepatic angiography and embolisation are often needed in high-grade liver injuries whether undergoing surgical or non-operative management. The multidisciplinary approach also includes procedures performed for biliary complications, such as percutaneous or endoscopic drainage of bile leaks.

Fluid and Electrolyte Disturbances in Critically Ill Patients

Disturbances in fluid and electrolytes are among the most common clinical problems encountered in the intensive care unit (ICU). Recent studies have reported that fluid and electrolyte imbalances are associated with increased morbidity and mortality among critically ill patients. To provide optimal care, health care providers should be familiar with the principles and practice of fluid and electrolyte physiology and pathophysiology. Fluid resuscitation should be aimed at restoration of normal hemodynamics and tissue perfusion. Early goal-directed therapy has been shown to be effective in patients with severe sepsis or septic shock. On the other hand, liberal fluid administration is associated with adverse outcomes such as prolonged stay in the ICU, higher cost of care, and increased mortality. Development of hyponatremia in critically ill patients is associated with disturbances in the renal mechanism of urinary dilution. Removal of nonosmotic stimuli for vasopressin secretion, judicious use of hypertonic saline, and close monitoring of plasma and urine electrolytes are essential components of therapy. Hypernatremia is associated with cellular dehydration and central nervous system damage. Water deficit should be corrected with hypotonic fluid, and ongoing water loss should be taken into account. Cardiac manifestations should be identified and treated before initiating stepwise diagnostic evaluation of dyskalemias. Divalent ion deficiencies such as hypocalcemia, hypomagnesemia and hypophosphatemia should be identified and corrected, since they are associated with increased adverse events among critically ill patients.

Urgent care in gynaecology: Resuscitation and management of sepsis and acute blood loss

Sepsis and/or acute blood loss can be encoutered as an emergency condition in gynaecology, especially in women with ectopic pregnancy/miscarriage, acute pelvic inflammatory disease (PID)/tuboovarian abscesses, post-puerperal sepsis/haemorrhage and even in postoperative scenarios. If underestimated or suboptimally treated, both can lead to an inadequate tissue perfusion (defined as shock) and the development of multi-organ failure. Morbidity and mortality after development of one of the shock syndromes (septic or haemorrhagic) correlates directly with the duration and severity of the malperfusion. The patient's prognosis depends on a prompt diagnosis of the presence of shock and immediate resuscitation to predefined physiological end-points, often before the cause of the shock has been identified. In septic shock, hypotension is primarily treated with fluid administration and eventually vasopressors, if required, in order to improve the circulation. Timely administration of antibiotics, control of infectious foci, appropriate use of corticoids and recombinant human activated protein C, tight glucose control, prophylaxis of deep vein thrombosis and stress ulcer prevention complete the therapy of septic shock. In haemorrhagic shock, the treatment primarily involves controlling haemorrhage, reversal of possible coagulopathy and administration of sufficient volumes of fluids and blood products to restore normal tissue perfusion.