Marker Of Perfusion Research Articles

Fetal major cardiac defects and placental dysfunction at 11-13 weeks' gestation.

To investigate the relationship between fetal major cardiac defects and markers of placental perfusion and function. This was a prospective screening study in singleton pregnancies at 11-13 weeks' gestation. Uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were measured and the values were converted into multiples of the normal median (MoM). Median MoM values in fetuses with isolated major cardiac defects were compared with those in fetuses without major defects. The 50 094 singleton pregnancies fulfilling the entry criteria included 49 898 pregnancies with normal cardiac anatomy and 196 (0.39%) with major congenital cardiac defects: 73 (37.2%) with conotruncal defects, 63 (32.1%) with left ventricular outflow tract defects and 60 (30.6%) with valvular defects. In the group with cardiac defects, compared with controls, there was lower median PAPP-A MoM (0.81 vs 1.00, P < 0.0001) and PlGF MoM (0.78 vs 1.00, P < 0.0001) but no significant difference in UtA-PI MoM (1.01 vs 1.00, P = 0.162). In pregnancies with isolated fetal major cardiac defects, there is evidence of placental dysfunction in the absence of impaired placental perfusion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Capillary refill time during fluid resuscitation in patients with sepsis-related hyperlactatemia at the emergency department is related to mortality.

IntroductionAcute circulatory dysfunction in patients with sepsis can evolve rapidly into a progressive stage associated with high mortality. Early recognition and adequate resuscitation could improve outcome. However, since the spectrum of clinical presentation is quite variable, signs of hypoperfusion are frequently unrecognized in patients just admitted to the emergency department (ED). Hyperlactatemia is considered a key parameter to disclose tissue hypoxia but it is not universally available and getting timely results can be challenging in low resource settings. In addition, non-hypoxic sources can be involved in hyperlactatemia, and a misinterpretation could lead to over-resuscitation in an unknown number of cases. Capillary refill time (CRT) is a marker of peripheral perfusion that worsens during circulatory failure. An abnormal CRT in septic shock patients after ICU-based resuscitation has been associated with poor outcome. The aim of this study was to determine the prevalence of abnormal CRT in patients with sepsis-related hyperlactatemia in the early phase after ED admission, and its relationship with outcome.MethodsWe performed a prospective observational study. Septic patients with hyperlactemia at ED admission subjected to an initial fluid resuscitation (FR) were included. CRT and other parameters were assessed before and after FR. CRT-normal or CRT-abnormal subgroups were defined according to the status of CRT following initial FR, and major outcomes were registered.ResultsNinety-five hyperlactatemic septic patients were included. Thirty-one percent had abnormal CRT at ED arrival. After FR, 87 patients exhibited normal CRT, and 8 an abnormal one. Patients with abnormal CRT had an increased risk of adverse outcomes (88% vs. 20% p<0.001; RR 4.4 [2.7–7.4]), and hospital mortality (63% vs. 9% p<0.001; RR 6.7 [2.9–16]) as compared to those with normal CRT after FR. Specifically, CRT-normal patients required less frequently mechanical ventilation, renal replacement therapy, and ICU admission, and exhibited a lower hospital mortality.ConclusionsHyperlactatemic sepsis patients with abnormal CRT after initial fluid resuscitation exhibit higher mortality and worse clinical outcomes than patients with normal CRT.

An assessment of ventilation and perfusion markers in out-of-hospital cardiac arrest patients receiving mechanical CPR with endotracheal or supraglottic airways

Aim of the studyMechanical chest compression (MCPR) devices are considered equivalent to manual compressions in patient outcomes in out-of-hospital cardiac arrest (OHCA). However, recent data suggest possible harm in patients with a supraglottic airway device (SGA) during MCPR. The aim of this study was to evaluate differences in direct and indirect markers of ventilation and perfusion in patients with cardiac arrest receiving MCPR and who had their airway managed with an endotracheal tube (ETT) or SGA. MethodsWe retrospectively reviewed Emergency Medical Services (EMS) agencies and emergency department (ED) records over a two-year period. We included patients with OHCA who underwent MCPR and who had an advanced airway placed. The primary outcome was differences in intra-arrest end-tidal carbon dioxide (etCO2) measurements. Secondary outcomes included intra-arrest ventilation rates, rates of prehospital return of spontaneous circulation (ROSC), blood pressure upon prehospital ROSC, and 24-h survival. ResultsValid data sets were available for 126 patients. Eighty-four (66.7%) had an ETT placed, and 42 (33.3%) had a SGA placed. Twenty-eight (22.6%) achieved prehospital ROSC. Twenty-four-hour survival data were available for 13 (10.3%) of these patients. There were no significant differences in primary or secondary outcomes. ConclusionIn this retrospective study, we found no evidence of differences in markers of ventilation, perfusion or prehospital ROSC and survival in patients with OHCA who had their airway managed with either an ETT or SGA while receiving MCPR.

Utilisation du vert d’indocyanine en chirurgie sénologique et reconstruction mammaire

The Indocyanine green (ICG) is a soluble dye that is eliminated by the liver and excreted in bile. When illuminated by an near-infrared light, the ICG emits fluorescence in the near-infrared spectrum, which can be captured by a near-infrared camera-handled device. In case of intravenous injection, ICG may be used as a marker of skin perfusion. In case of interstitial injection, it may be useful for lymphatic network mapping. In oncological and reconstructive breast surgery, ICG is used for sentinel lymph node identification, to predict mastectomy skin flap necrosis, to assess the perfusion of free flaps in autologous reconstruction and for diagnosis and treatment of upper limb secondary lymphedema. Intraoperative indocyanine green fluorescence might also be used to guide the excision of nonpalpable breast cancer.

QTc prolongation, increased NT-proBNP and pre-clinical myocardial wall remodeling in excessive alcohol consumers: The SABPA study.

Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption - measured via ethnic-specific gamma glutamyl transferase (γ-GT) cut-points - and markers of cardiac perfusion, electrical activity, and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic cohort (n=405). Alcohol consumption was determined according to previously defined ethnic-specific γ-GT cut-points, where γ-GT≥19.5U/L and γ-GT≥55U/L indicated excessive alcohol consumption in Caucasians and Africans, respectively. Ambulatory 24-h blood pressure and electrocardiograms (ECG), 10-lead ECG left ventricular hypertrophy (LVH), ischemic events, N-terminal pro-brain natriuretic peptide (NT-proBNP), and QTc prolongation were assessed. Fasting blood samples were obtained. A poorer cardio-metabolic profile and mean 24-h hypertensive and ECG-LVH values were evident in high γ-GT groups of both ethnicities, when compared to their low counterparts. The African high γ-GT group reported a higher intake of alcohol and presented significant increases in NT-proBNP (p<0.001), QTc prolongation (p=0.008), and ischemic events (p=0.013). Regression analyses revealed associations between ECG-LVH and NT-proBNP, QTc prolongation, ischemic events, and SBP, in the African high γ-GT group exclusively. High alcohol consumers presented delayed electrical conduction in the heart accompanied by ECG-LVH, ischemic events, and increased vaso-responsiveness, predominantly in Africans. Ultimately, increased left ventricular distension on a pre-clinical level may elevate the risk for future cardiovascular events in this population.

Urinary liver-type fatty acid-binding protein is associated with subendocardial viability ratio in middle- and older-aged adults

ABSTRACTBackground: To identify one of the physiological underlying mechanisms of the predictive effects of urinary liver-type fatty acid-binding protein (L-FABP) for the onset of cardiovascular disease (CVD), we investigated the relationship between urinary L-FABP levels and subendocardial viability ratio (SEVR), a marker of myocardial perfusion, in middle- and older-aged adults.Methods: This was a cross-sectional study of 249 middle- and older-aged adults (aged 46–83 years). We measured urinary L-FABP levels and central hemodynamic parameters, including SEVR, calculated by pulse wave analysis using an applanation tonometry.Results: In the participants stratified in accordance with the tertiles of urinary L-FABP levels, SEVR decreased in a stepwise fashion with increasing tertiles (p < 0.001). Furthermore, this association remains significant after the consideration of various confounders. On the contrary, urinary albumin levels were not independently related with SEVR.Conclusion: Our results demonstrated that urinary L-FABP levels were independently associated with the SEVR of the middle- and older-aged adults. This result suggests that the increase in urinary L-FABP levels even within the normal range might be related to the decrease in myocardial perfusion (SEVR).

Plasma succinate is a predictor of mortality in critically injured patients.

Trauma is the leading cause of mortality under the age of 40 years. Recent observations on metabolic reprogramming during hypoxia and ischemia indicate that hypoxic mitochondrial uncoupling promotes the generation of succinate, which in turn mediates reperfusion injury and inflammatory sequelae upon reoxygenation. Plasma levels of succinate significantly increase in response to trauma and hemorrhage in experimental models and clinical samples, suggesting that succinate may represent a candidate marker of systemic perfusion in trauma. Quantitative mass spectrometry-based metabolomics was used to quantify succinate and lactate in 595 plasma samples from severely injured patients enrolled at the Denver Health Medical Center, a Level I trauma center in Denver, Colorado. A total of 95 severely injured patients were sampled for up to 10 time points (595 total samples), from field blood to 7 days postinjury. Results indicate that plasma levels of succinate increased up to 25.9-fold in deceased patients versus the median of the surviving patients (p = 2.75e-100; receiver operating characteristic area under the curve, 0.911). On the other hand, only 2.4-fold changes increases in lactate were observed (p = 5.8e-21; area under the curve, 0.874). Succinate represents a uniquely sensitive biomarker of postshock metabolic derangement and may be an important mediator of sequelae. Prognostic study, level III.

Intraoperative Cerebral Perfusion Disturbances During Transcatheter Aortic Valve Replacement

Transcatheter aortic valve replacement entails profound and unavoidable hemodynamic perturbations that may contribute to the neurological injury associated with the procedure. Thirty-one patients were monitored with cerebral oximetry as a surrogate marker of perfusion while undergoing transcatheter aortic valve replacement via a transfemoral approach under general anesthesia to detect intraoperative hypoperfusion insult. Serial neurologic, cognitive, and cerebral magnetic resonance imaging assessments were administered to objectively quantify perioperative neurologic injury and ascertain any association with significant cerebral oximetry disturbances. Cerebral oximetry reacted promptly to rapid ventricular pacing with significant cerebral desaturation, relative to baseline, of greater than 12% and greater than 20% in 12 of 31 (68%) and 9 of 31 (29%) patients, respectively; or to an absolute measurement of less than 50% in 10 of 31 (33%) patients. Hyperemia occurred immediately following relief of aortic stenosis exceeding baseline by greater than 10% and greater than 20% in 14 of 31 (45%) and 5 of 31 (16%) patients. Postoperative cognitive dysfunction was evident in 3 of 31 (10%) patients and new magnetic resonance imaging-defined ischemic lesions were seen in 17 of 28 (61%) patients. No patient experienced clinically apparent stroke. Cerebral oximetry reacted promptly to rapid ventricular pacing with significant desaturation and hyperemia a common occurrence. However, no association between this intraoperative insult and objective neurologic injury was detected.

Characterization of viability, scarring and hibernation of the myocardium supplied by epicardial coronary arteries with low flow grades.

The aim of this study was to analyse the relationship between reduced coronary artery flow and myocardial viability, scarring and hibernation. Coronary flow grades and collateral vessels were scored using the thrombolysis in myocardial infarction trial (TIMI) and the Rentrop and Cohen scoring systems, respectively. N-ammonia and fluorine-18-fluorodeoxyglucose (F-FDG) are the perfusion and metabolic markers on PET, respectively. The left ventricle was divided into three coronary territories. The area with the highest N-ammonia uptake was considered the reference region. Myocardial regions with F-FDG uptake of at least 50% of the reference region were considered viable and those with F-FDG uptake less than 50% of the reference region were considered scarred. Hibernation was considered present if the viable myocardium had significant wall motion abnormality. There were 80 (71 males) patients with 240 myocardial territories. TIMI 2-3 arteries supplied 151 regions (group A), and 89 regions were supplied by TIMI 0-1 arteries (group B). Viable myocardium was present in 140 (93%) regions of group A and in 76 (85%) regions of group B (P=0.068). Scarring was present in 40 (26%) regions in group A and in 49 (55%) regions in group B (P<0.0001). Wall motion data were available in 215 regions: 133 regions in group A and 82 regions in group B. Hibernating myocardium was predicted in 36 (28%) regions in group A and in 34 (41%) regions in group B (P<0.05). Myocardial regions supplied by arteries with TIMI 0-1 are characterized by significantly increased incidence of hibernation and scarring. Video abstract: http://links.lww.com/NMC/A115.

Monitoring the Vascular Response and Resistance to Sunitinib in Renal Cell Carcinoma In Vivo with Susceptibility Contrast MRI.

Antiangiogenic therapy is efficacious in metastatic renal cell carcinoma (mRCC). However, the ability of antiangiogenic drugs to delay tumor progression and extend survival is limited, due to either innate or acquired drug resistance. Furthermore, there are currently no validated biomarkers that predict which mRCC patients will benefit from antiangiogenic therapy. Here, we exploit susceptibility contrast MRI (SC-MRI) using intravascular ultrasmall superparamagnetic iron oxide particles to quantify and evaluate tumor fractional blood volume (fBV) as a noninvasive imaging biomarker of response to the antiangiogenic drug sunitinib. We also interrogate the vascular phenotype of RCC xenografts exhibiting acquired resistance to sunitinib. SC-MRI of 786-0 xenografts prior to and 2 weeks after daily treatment with 40 mg/kg sunitinib revealed a 71% (P < 0.01) reduction in fBV in the absence of any change in tumor volume. This response was associated with significantly lower microvessel density (P < 0.01) and lower uptake of the perfusion marker Hoechst 33342 (P < 0.05). The average pretreatment tumor fBV was negatively correlated (R2 = 0.92, P < 0.0001) with sunitinib-induced changes in tumor fBV across the cohort. SC-MRI also revealed suppressed fBV in tumors that acquired resistance to sunitinib. In conclusion, SC-MRI enabled monitoring of the antiangiogenic response of 786-0 RCC xenografts to sunitinib, which revealed that pretreatment tumor fBV was found to be a predictive biomarker of subsequent reduction in tumor blood volume in response to sunitinib, and acquired resistance to sunitinib was not associated with a parallel increase in tumor blood volume. Cancer Res; 77(15); 4127-34. ©2017 AACR.

Perfusion monitoring and intraventricular hemorrhage in preterm infants.

Cardiovascular instability in preterm infants during the early postnatal period correlates with the development of intraventricular hemorrhage (IVH). Due to the correlation between hypotension and fluctuation of blood pressure, treatment was targeted specifically at hypotension to prevent IVH, but this was not successful. Recently, several novel perfusion markers have been found to be correlated with the development of IVH, and they are of current interest in cardiovascular management. In this review, the correlation between IVH and conventional, as well as novel, perfusion markers is examined.

Echocardiographic Inferior Vena Cava Measurement As An Alternative to Central Venous Pressure Measurement in Neonates.

To evaluate the correlation between echocardiographic inferior vena cava (IVC) measurements and central venous pressure (CVP) in neonates. Also, to evaluate the correlation between IVC measurements and gestational age (GA) and body weight (BW). Thiscross sectional analytical studywas conducted from June 2014 through June 2016 in a level III NICU. All neonates requiring intensive hemodynamic monitoring and having umbilical venous catheter (UVC) in place for clinical indications were enrolled in the study. IVC measurements were recorded by echocardiography (ECHO) and CVP was measured concomitantly in neonates having appropriate sized UVC in place. IVC measurements were evaluated and compared for any correlation with the CVP, GA and BW. Fifty neonates with median gestation of 37 wk [Q1=29.2, Q3=37.8, interquartile range (IQR)=8.6 wk] and median birth weight of 2420g (Q1=923.5, Q3=2850, IQR=1926.5g) were included in the study. A strong negative linear correlation was observed between IVC collapsibility index (IVC-CI) and CVP (r=-0.968, r2=-0.937, p 0.000). No correlation was observed between IVC-CI and GA or BW. IVC minimum and IVC maximum diameters did not correlate with CVP but correlated well with GA and BW. Echocardiographic IVC-CI measurement has a good correlation with CVP measurement in neonates. The clinical use will depend on the ability of IVC-CI to predict surrogate markers of tissue perfusion in shock.

Monitoring and End-Points of Trauma Resuscitation

Monitoring end-points of trauma resuscitation and understanding principles of hemostatic resuscitation have become important in the management of severely injured patients. The purpose of this review is to discuss a selected number of parameters used to guide resuscitation of trauma patients. In trauma, shock occurs because of inadequate tissue perfusion and oxygen delivery. The goal of resuscitation is to restore adequate tissue perfusion while avoiding over-resuscitation and associated complications. Understanding of the dynamic cardiopulmonary interactions provides the physician with a tool to evaluate pulse pressure variation and stroke volume variation. Measurements of mixed and central venous oxygen saturation give an indication of systemic oxygen extraction. Bedside echocardiography has dramatically improved the diagnostic evaluation of patients in shock. The metabolic markers of perfusion are indicators of micro-circulation resuscitation and include characterization of oxygen extraction, lactate production, and base deficit. Characterization of regional oxygen delivery is an evolving field with new technological developments. Despite the numerous measures used to characterize end-points of trauma resuscitation, there is no clear single measure used to guide optimal resuscitation. The physician must provide careful interrogation of hemodynamic, metabolic, and hemostatic parameters and their respective trends over time to establish optimal therapy. The use of thromboelastography to guide hemostatic resuscitation has the potential to optimize individual patient resuscitation thereby reducing unnecessary blood product utilization. Careful monitoring of end-points of trauma resuscitation and understanding of hemostatic resuscitation are needed to guide resuscitation of critically ill patients and improve outcomes.

Simultaneous In Vivo Fluorescent Markers for Perfusion, Protoporphyrin Metabolism, and EGFR Expression for Optically Guided Identification of Orthotopic Glioma.

Purpose: While extent of tumor resection is an important predictor of outcome in glioma, margin delineation remains challenging due to lack of inherent contrast between tumor and normal parenchyma. Fluorescence-guided surgery is promising for its ability to enhance contrast through exogenous fluorophores; however, the specificity and sensitivity of the underlying contrast mechanism and tumor delivery and uptake vary widely across approved and emerging agents.Experimental Design: Rats with orthotopic F98 wild-type and F98 EGFR-positive (EGFR+) gliomas received in vivo administration of IRDye680RD, 5-aminioleuvulinic acid, and ABY-029-markers of perfusion, protoporphyrin metabolism, and EGFR expression, respectively. Ex vivo imaging demonstrates the contrast mechanism-dependent spatial heterogeneity and enables within-animal comparisons of tumor-to-background ratio (TBR).Results: Generally, ABY-029 outperformed PpIX in F98EGFR orthotopic tumor margins and core (50% and 60% higher TBR, respectively). PpIX outperformed ABY-029 in F98wt margins by 60% but provided equivalent contrast in the bulk tumor. IRDye680RD provided little contrast, having an average TBR of 1.7 ± 0.2. The unique spatial patterns of each agent were combined into a single metric, the multimechanistic fluorescence-contrast index (MFCI). ABY-029 performed best in EGFR+ tumors (91% accuracy), while PpIX performed best in wild-type tumors (87% accuracy). Across all groups, ABY-029 and PpIX performed similarly (80% and 84%, respectively) but MFCI was 91% accurate, supporting multiagent imaging when tumor genotype was unknown.Conclusions: Human use of ABY-029 for glioma resection should enhance excision of EGFR+ tumors and could be incorporated into current PpIX strategies to further enhance treatment in the general glioma case. Clin Cancer Res; 23(9); 2203-12. ©2016 AACR.

ASSOCIATION BETWEEN RETINAL HEMORRHAGIC PATTERNS AND PERFUSION STATUS IN EYES WITH ACUTE CENTRAL RETINAL VEIN OCCLUSION

To evaluate peripheral retinal hemorrhagic patterns in eyes with acute central retinal vein occlusion, and to explore their clinical relevance in differentiating for the retinal perfusion status, through a prospective, and cross-sectional study. Fifty eyes with acute central retinal vein occlusion were included. Retinal hemorrhagic patterns at the equator and retinal perfusion status were evaluated by ultra-wide field fundus photography and fluorescein angiography. Retinal perfusion was categorized as nonischemic in 29 eyes, ischemic in 18 eyes, and undeterminable in 3 eyes. None of the examined eyes had flame-shaped retinal hemorrhages in the periphery. All hemorrhages were rounded-dot or blot and were variable in size. Particle analysis was performed to quantify hemorrhage size, and showed higher values in eyes having larger blot hemorrhages, and lower values in eyes having dot or smaller blot hemorrhages. Mean size of maximum peripheral dot or blot hemorrhage was larger in eyes classified as ischemic (10,763.0 ± 5,946.3 pixels) than as nonischemic (2,839.9 ± 1,153.6 pixels, P < 0.001). The authors calculated area under the curve to investigate the ability of continuous variables to discriminate retinal perfusion status, which was 0.963 (P < 0.001) for mean size of maximum peripheral blot hemorrhages. The authors objectively evaluated retinal hemorrhagic patterns at the equator in eyes with acute central retinal vein occlusion using particle analysis. The resulting hemorrhage size measurement was considered to be often useful in determining retinal perfusion status. Because they can be noninvasively evaluated with readily available equipment, peripheral hemorrhagic patterns might be good clinical markers of retinal perfusion.

We No Longer Need to Stress Ulcer Prophylaxis in the Critically Ill

Preventing stress gastropathy has been a mainstay in the management of critically ill patients for decades. A landmark trial in 1994 identified the most significant risk factors for stress gastropathy as mechanical ventilation for greater than 48 h and primary coagulopathy. Since this study's publication more than two decades ago, the incidence of clinically significant gastrointestinal bleeding secondary to stress gastropathy has significantly declined. In addition, the most widely used agents for prophylaxis have been associated with an increasing number of adverse effects, including myocardial infarction, Clostridium difficile infection, osteoporosis and ventilator associated pneumonia. As the incidence of significant bleeding decreases and the knowledge about prophylaxis-related adverse events increases, it is necessary to revisit current clinical practice. Major practice changes, including early aggressive fluid resuscitation and development of dynamic markers for volume status, have reduced the likelihood for prolonged hypoperfusion states. Additionally, the recognition of the important of enteral nutrition early in the ICU stay encourages mesenteric perfusion and reduces risk for development of ischemic damage. Contemporary studies have failed to replicate significant rates of gastrointestinal bleeding, likely in part due to these advances in care. Recent studies, including a pilot randomized trial, are questioning the necessity of pharmacologic prophylaxis in the modern era, with undetectable rates of gastrointestinal bleeding in enrolled patients. Patients with risk factors for stress gastropathy who demonstrate no evidence of splanchnic hypoperfusion may not benefit from receiving stress ulcer prophylaxis and tolerance of enteral nutrition may be used as a surrogate marker for adequate perfusion. Overall there is a lack of high quality data supporting stress ulcer prophylaxis in the modern era.

Effect of Dexamethasone on Resting Blood Lactate Concentrations in Horses.

BackgroundBlood lactate concentration is a marker of tissue perfusion and helps guide therapeutic interventions in critically ill horses. In both humans and dogs, administration of corticosteroids can increase blood lactate concentration, leading to type B hyperlactatemia. This effect could be a consequence of the impact of corticosteroids on glucose metabolism.ObjectivesTo investigate the effects of daily IM dexamethasone administration on blood lactate and glucose concentrations in horses.AnimalsNine healthy adult horses.MethodsA randomized, blinded, controlled, cross‐over study design was used. Horses were randomly assigned to 1 of 2 groups, either receiving 0.05 mg/kg of dexamethasone IM or an equivalent volume of saline, daily for 7 days. Blood was collected to determine lactate and glucose concentrations at baseline, 2 hours after the daily injections and 24 hours after the last injection.ResultsDexamethasone treatment had a statistically significant effect on lactate (P = .006) and glucose (P = .033) concentrations. The least squares mean lactate concentration was 0.93 mmol/L (95% CI: 0.87–0.99) in the dexamethasone group compared to 0.71 mmol/L (95% CI: 0.70–0.73) for the saline group. A positive relationship between blood lactate and glucose concentrations was identified, with a 0.07 mmol/L (95% CI: 0.05–0.09) increase in lactate concentration per unit increase in glucose (P < .0001) concentration.Conclusions and Clinical ImportanceDexamethasone induces statistically significant increases in blood lactate and glucose concentrations in healthy horses. Awareness of the potential for corticosteroids to induce type B hyperlactatemia might be important in the management of critically ill horses receiving dexamethasone.

Ten concerns about blood pressure measurement and targets in paediatric sepsis.

Current paediatric sepsis guidelines suggest that resuscitation is titrated against clinical markers of hypovolaemia and end organ perfusion [1], including blood pressure (BP), heart rate and capillary refill time (CRT). BP is used both as a defining feature of shock and as a target for therapy. This paper will focus on the measurement of BP, the definition of hypotension and on the target BP for therapy in children with sepsis.

The REFLO-STEMI (REperfusion Facilitated by LOcal adjunctive therapy in ST-Elevation Myocardial Infarction) trial: a randomised controlled trial comparing intracoronary administration of adenosine or sodium nitroprusside with control for attenuation of microvascular obstruction during primary percutaneous coronary intervention

BackgroundMicrovascular obstruction (MVO) predicts short- and longer-term outcomes following primary percutaneous coronary intervention (PPCI) treatment of ST-elevation myocardial infarction (STEMI). The evidence base supporting the role of adenosine and sodium nitroprusside (SNP), the most evaluated adjunctive therapies aimed at attenuating MVO and infarct size, remains weak as the trials involved have had variable end points and used differing drug doses and modes of delivery.ObjectiveTo determine whether intracoronary administration of adenosine or SNP following thrombus aspiration reduces infarct size and/or MVO measured by cardiac magnetic resonance (CMR) imaging in patients undergoing PPCI within 6 hours of onset of STEMI.DesignMulticentre, prospective, parallel, randomised controlled and open-label trial with blinded end point analysis.SettingFour high-volume UK PPCI centres.ParticipantsPatients with STEMI undergoing PPCI with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0/1 in the infarct-related artery and no significant bystander coronary artery disease on angiography.InterventionsParticipants were anticoagulated with bivalirudin and allocated by an automated 24-hour telephone randomisation service to one of three groups: (1) standard PPCI (control), (2) PPCI with adjunctive adenosine 1–2 mg or (3) PPCI with adjunctive SNP 250 µg. The study drugs were delivered intracoronary immediately following thrombus aspiration and again following successful stenting.Main outcome measuresThe primary outcome was infarct size (% total left ventricular end-diastolic mass; %LVM) measured by CMR imaging undertaken 48–96 hours post PPCI. Secondary outcome measures included MVO (hypoenhancement within the infarct core) on CMR imaging, electrocardiographic and angiographic markers of microvascular perfusion and major adverse cardiac events (MACEs) during a median of 6 months’ follow-up. The study aimed to recruit 240 patients (powered at 80% to detect a 5% absolute reduction in infarct size).ResultsThe trial completed recruitment in April 2014 having randomised 247 patients (standard PPCI group,n = 86; PPCI + adenosine group,n = 82; PPCI + SNP group,n = 79). In total, 79% of participants were male and the mean ± standard deviation age of participants was 59.3 ± 12.3 years. CMR imaging was completed in 197 (80%) patients (standard PPCI,n = 65; PPCI + adenosine,n = 63; PPCI + SNP,n = 69) for the primary outcome. There was no significant difference in infarct size [%LVM, median, interquartile range (IQR)] between the adenosine group (10.1, 4.7–16.2), the SNP group (10.0, 4.2–15.8) and the control group (8.3, 1.9–14.0) (p = 0.062 andp = 0.160 vs. control, respectively). MVO (%LVM, median, IQR) was similar across the groups [1.0, 0.0–3.7 (p = 0.205) and 0.6, 0.0–2.4 (p = 0.244) for adenosine and SNP, respectively, vs. 0.3, 0.0–2.8 for the control]. Using per-protocol analysis, infarct size (%LVM) was increased in adenosine-treated patients compared with control patients (12.0 vs. 8.3;p = 0.031). Increased left ventricular volume and reduced left ventricular ejection fraction were also observed in the adenosine arm. There was a significant increase in MACEs in patients undergoing adenosine-facilitated PPCI compared with control patients, driven by heart failure, at 30 days [hazard ratio (HR) 5.39, 95% confidence interval (CI) 1.18 to 24.60;p = 0.04] and 6 months (HR 6.53, 95% CI 1.46 to 29.2;p = 0.01) post randomisation.ConclusionsHigh-dose intracoronary adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR imaging. Furthermore, adenosine may adversely affect mid-term clinical outcome and should not be used during PPCI to prevent reperfusion injury.Trial registrationClinicalTrials.gov NCT01747174 and EudraCT 2010–023211–34.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

α‐trideuteromethyl[15N]glutamine: A long‐lived hyperpolarized perfusion marker

PurposeWe characterized the performance of a novel hyperpolarized perfusion marker, α‐trideuteromethyl[15N]glutamine, for direct comparison with a 13C‐based hyperpolarized perfusion marker, [13C, 15N2]urea.MethodsA hardware platform and pulse sequence for in vivo 15N experiments were established. Hyperpolarized solutions of α‐trideuteromethyl[15N]glutamine and [13C, 15N2]urea were injected into healthy male Lewis rats. Kidney slice images were acquired using a single‐shot spiral readout. Both compounds were compared to determine in vivo signal lifetime and tracer distribution. Mass spectrometry was performed to evaluate excretion of the compound.ResultsCompared with 13C‐labeled urea, a significantly increased signal lifetime was observed. While the urea signal was gone after 90 s, decay of the glutamine compound was sufficiently slow to obtain a quantifiable signal, even after 5 min. The glutamine derivative showed strong localization in the kidneys with little background signal. Effective T1 of α‐trideuteromethyl[15N]glutamine was approximately eight‐fold higher than that of urea. Mass spectrometry results confirmed rapid excretion within the time scale of the measurement.ConclusionHyperpolarized α‐trideuteromethyl[15N]glutamine is a highly promising candidate for renal studies because of its long signal lifetime, strong localization and rapid excretion. Magn Reson Med 76:1900–1904, 2016. © 2016 International Society for Magnetic Resonance in Medicine