Femoral Artery Catheterization Research Articles

Differential benefits of physical training associated or not with l-arginine supplementation in rats with metabolic syndrome: Evaluation of cardiovascular, autonomic and metabolic parameters

Metabolic syndrome (MetS) is characterized by endocrine-metabolic and cardiac alterations that increase the risk of cardiovascular disease, dyslipidemia, and type-2 diabetes mellitus. Dietary supplementation with l-Arginine (L-Arg) is beneficial for fat loss, while chronic aerobic exercise has several benefits in reversing cardiovascular, autonomic, and metabolic dysfunctions caused by obesity. However, the association between these two approaches has not yet been described. This study aimed to evaluate the possible benefits of physical training, with or without l-Arg-supplementation, on cardiovascular, autonomic, and metabolic parameters in rats with MetS, which was induced by the subcutaneous administration of monosodium glutamate at 4 mg g−1day−1 in rats from the first to fifth day of life. Physical training on a treadmill and supplementation with l-Arg-in adulthood were carried out concomitantly for 8 weeks. After this, the animals underwent femoral artery catheterization to record their cardiovascular parameters and autonomic modulation. Organs and blood were removed to measure levels of nitrite, glucose, and hepatic steatosis. In adult rats with MetS, supplementation with l-Arg-in combination with physical training reduced hypertension, tachycardia, adipose tissue mass, free fatty acids, and hepatic steatosis. Supplementation with l-Arg-and physical training separately was beneficial in reducing several aspects of MetS, but a combination of both was especially effective in reducing adipose tissue and hepatic steatosis. Together, the two therapies can form a good strategy to combat MetS.

Frequency and Predictors of Acute and Persistent Femoral Artery Occlusion in Infants with Congenital Heart Disease: A Study Using Ultrasonography for Arterial Access and the Diagnosis of Arterial Occlusion.

Femoral arterial access is challenging in infants. Furthermore, after cardiac catheterization, femoral arterial occlusion (FAO) can be underestimated and easily missed on physical examination. Ultrasound is recommended for femoral arterial access and the correct diagnosis of FAO; however, few studies have reported its effectiveness.To investigate the frequency and risk factors of acute loss of the arterial pulse (ALAP) and persistent femoral arterial occlusion (PFAO) in infants with congenital heart disease who underwent ultrasound-guided femoral arterial access (US-GFAA) and were diagnosed with FAO by ultrasound.We obtained data related to patient characteristics, access variables of US-GFAA, and ultrasonography findings of the femoral artery from our pediatric cardiac catheterization database between August 2017 and August 2022. We divided the patients into groups based on the presence of ALAP and PFAO. We identified ALAP in 99 (19%) patients and PFAO in 21(4%) of 522 patients in the study. The median patient age was 132days (interquartile range: 75-202days). The logistic regression analysis identified younger age, aortic coarctation, previous catheterization of the same femoral artery, larger sheath size (5F), and longer duration of cannulation as independent risk factors for ALAP and younger age as an independent risk factor for PFAO (all p < 0.05). This study showed that younger age at procedure was a risk factor for both ALAP and PFAO, while aortic coarctation, previous arterial catheterization, use of a larger sheath and longer duration of cannulation were risk factors for ALAP in infants. The majority of FAO is reversible and secondary to arterial spasm, and the of FAO increases inversely with patient age.

The first endovascular rat glioma model for pre-clinical evaluation of intra-arterial therapeutics.

Several translational animal models have been described assessing intra-arterial (IA) treatments for malignant gliomas. We describe the first endovascular animal model that allows testing of IA drug delivery as a first-line treatment, which is difficult to do in actual patients. We report a unique protocol for vascular access and IA delivery in the rat model that, unlike prior reports, does not require direct puncture and opening of proximal cerebrovasculature which carries risk of ischemia in the animal brain post-delivery. Wistar rats underwent left femoral artery catherization with a Balt Magic 1.2F catheter or Marathon Flow directed 1.5F Microcatheter with an Asahi Chikai 0.008 micro-guidewire which was navigated to the left internal carotid artery under x-ray. 25% mannitol was administered to test blood brain barrier breakdown (BBBB). Additional rats were implanted with C6 glioma cells in the left frontal lobe. C6 Glioma-Implanted Rats (C6GRs) were monitored for overall survival and tumor growth. Tumor volumes from MRI images were calculated utilizing 3D slicer. Additional rats underwent femoral artery catheterization with Bevacizumab, carboplatin, or irinotecan injected into the left internal carotid artery to test feasibility and safety. A successful endovascular access and BBBB protocol was established. BBBB was confirmed with positive Evans blue staining. 10 rats were successfully implanted with C6 gliomas with confirmed growths on MRI. Overall survival was 19.75 ± 2.21 days. 5 rats were utilized for the development of our femoral catheterization protocol and BBBB testing. With regards to IA chemotherapy dosage testing, control rats tolerated targeted 10 mg/kg of bevascizumab, 2.4 mg/kg of carboplatin, and 15 mg/kg of irinotecan IA ICA injections without any complications. We present the first endovascular IA rat glioma model that allows selective catheterization of the intracranial vasculature and assessment of IA therapies for gliomas without need for access and sacrifice of proximal cerebrovasculature.

Intravenous administration of apeling-13 induces a depressor response by releasing an unidentified substance

Apelin and APJ receptor play an important role in the regulating cardiovascular function; however, conflicting results have been reported regarding the effect of apelin on cardiovascular regulation. In this study, blood pressure and heart rate were measured by femoral arterial catheterization; and cardiac contractility was recorded by left ventricular catheterization through the right carotid artery in rats before and after intravenous administration of [pyr1]-apelin-13. The results show that intravenous administration of apelin-13 caused a dramatic reduction in BP but did not significantly alter heart rate and contractility. To study the mechanism of the apelin-induced depressor response, isometric tension was measured in isolated mesenteric arteries using a myograph approach. Surprisingly, treatment of the arteries with [pyr1]-apelin-13 did not cause relaxation of mesenteric arteries preconstricted with norepinephrine; however, treatment with plasma collected from rats that received intravenous administration of [pyr1]-apelin-13 caused pronounced relaxation of isolated arteries. Incubation with the guanylyl cyclase inhibitor, ODQ, blocked NO-induced relaxation, but did not significantly alter the relaxation response to the plasma from apelin-treated rats. Taken together, these findings demonstrate that intravenous injection of apelin causes a significant depressor response that is mediated by a NO-independent mechanism involving an unidentified substance released into the bloodstream leading to vasodilation.

The effects of excess salt intake on the kidney metabolism in normal Sprague Dawley rats.

Introduction: This study aimed to determine the effects of a high salt diet upon the metabolism of O 2 and substances in the kidney in normal Sprague Dawley (SD) rats. Methods were developed enabling the intermittent collection of renal arteriovenous (A-Vr) blood and urine samples and to measure renal blood flow (RBF) and arterial pressure (BP) in conscious freely moving rats with GFR determined in a separate group of conscious rats. Other groups were studied to obtain cortical (Cx) and outer medullary (OM) tissue samples for associated transcriptomic and metabolomic profiles. Methods: SD rats were instrumented with a renal arterial ultrasonic flow probe, a femoral arterial and renal venous catheters, and RBF and BP measured continuously (24/7). Arterial (A) and renal venous (Vr) blood and urine were collected repeatedly before and 7, 14, and 21 days after increasing the salt diet from 0.4% (LS) to 4% (HS) NaCl. GFR was measured in age-matched rats and used as control shams for normalization. Blood O 2 content was determined by radiometry. A global metabolomic analysis was performed on plasma and Cx and OM tissue samples at JAX laboratories (Thermo Q-Exactive Orbitrap coupled to Vanquich UPLC system) and together with mRNAseq analysis for Cx and OM by Novogene Inc. Results: BP increased less than 5 mmHg by day 3 of the HS diet while RBF rose nearly 20% (P&lt;0.05) and both were sustained at this level throughout the study. O 2 delivery, O 2 consumption (VO 2 ) and O 2 extraction rose over the 21 days of the HS diet (P&lt;0.05). Total GFR increased from 0.64 to 0.83 mL/min/100 g bw (P&lt;0.05) at HS 7 and remained elevated at HS 21. Whole kidney Na + reabsorption and kidney VO 2 were highly correlated positively (r=0.99). A sparse partial least squares discriminant analysis (sPLS-DA) of metabolomics for each of the 4 modes (C18 +/- and HILIC +/-) revealed clear distinctions between LS, HS14, and HS21 within Cx and OM. The mRNAseq tissue analysis found that the HS diet resulted in reduced expression of genes related to the TCA cycle and metabolism of amino acids and fatty acids. This was consistent with the metabolomic data showing a reduction of tissue citrate and succinate levels. In contrast, glycolysis-related genes including hexokinase, pyruvate kinase and lactate dehydrogenase were upregulated in the Cx tissue by HS. Minimal changes in metabolic pathways were observed in the OM tissue. A-Vr x RBF enabled metabolomic flux determination which showed the release of glucose on LS fed rats which was not evident with the HS diet. Uptake of citrate which was seen on LS was less evident on HS but there was a clear tendency observed for increased release of lactate, pyruvate, and α-ketoglutarate. Conclusions: Normal SD rats fed a HS underwent changes of RBF, O 2 extraction and utilization of metabolic substrates, most notably transitioning ATP production predominantly driven from TCA cycle to non-TCA cycle pathways which we are currently exploring more deeply. HL-116264, HL-151587 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism

IntroductionAvailable studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. The current study aimed to evaluate the effects of iNOS inhibition on cardiovascular and autonomic function in animals that were subjected to Parkinsonism by the administration of 6-OHDA. Materials and methodsThe animals underwent stereotaxic surgery for bilateral microinfusion of the neurotoxin 6-OHDA (6 mg/mL in 0.2% ascorbic acid in sterile saline solution) or vehicle solution for the Sham group. From the day of stereotaxis until the day of femoral artery catheterization, the animals were treated with the iNOS inhibitor, S-methylisothiourea (SMT; 10 mg/kg; i. p.) or saline solution (0.9%; i. p.) for 7 days. The animals were divided into four groups: Sham-Saline, Sham-SMT, 6-OHDA-Saline, and 6-OHDA-SMT. Subsequent analyses were performed on these four groups. After 6 days, they underwent catheterization of the femoral artery, and 24 h later, mean arterial pressure (MAP) and heart rate (HR) were recorded. Another group of animals (the 6-OHDA and Sham groups) was assessed for aortic vascular reactivity after 7 days of bilateral infusion of 6-OHDA or vehicle, in which cumulative concentration-effect curves (CCEC) were made for phenylephrine (Phenyl), acetylcholine and sodium nitroprusside (NPS). Also, CCEC in the presence of Nw-nitro-arginine-methyl-ester (l-NAME) (10-5 M), SMT (10-6 M), and indomethacin (10-5 M) blockers were made. ResultsThe effectiveness of the 6-OHDA lesion was confirmed with the reduction of DA in 6-OHDA animals. However, treatment with SMT could not reverse the loss of DA. Concerning the baseline parameters, SBP and MAP values were lower in 6-OHDA animals compared to their Sham control, with no effect of treatment with SMT. In the analysis of SBP variability, a decrease in variance, the VLFabs component, and the LFabs component were observed in the 6-OHDA groups when compared to their controls, regardless of treatment with SMT. It was also observed that intravenous injections of SMT resulted in an increase in BP and a decrease in HR. However, the response was not different between the Sham and 6-OHDA groups. In vascular function, there was a hyporeactivity to Phenyl in the 6-OHDA group, and when investigating the mechanisms of this hyporeactivity, it was seen that the Rmax to Phenyl increased with incubation with SMT, indicating that iNOS could be involved in the vascular hyporeactivity of animals with Parkinsonism. ConclusionThus, the set of results presented in this study suggests that part of the cardiovascular dysfunction in animals subjected to 6-OHDA Parkinsonism may be peripheral and involve the participation of endothelial iNOS.

Noninvasive Assessment of Arterial Pulse-Pressure Variation During General Anesthesia: Clinical Evaluation of a New High-Fidelity Upper Arm Cuff

To compare noninvasive pulse-pressure variation (PPV) measurements obtained from a new high-fidelity upper arm cuff using a hydraulic coupling technique to corresponding intraarterial PPV measurements. The authors used prospective multicenter comparison and development studies for the new high-fidelity upper arm cuff. The study was performed in the departments of Anesthesiology at the Ludwig-Maximilians-Universität München Hospital, the University Hospital of Bonn, and the RoMed Hospital in Rosenheim (all Germany). A total of 153 patients were enrolled, undergoing major abdominal surgery or neurosurgery with mechanical ventilation. For the evaluation of PPV, 1,467 paired measurements in 107 patients were available after exclusion due to predefined quality criteria. Simultaneous measurements of PPV were performed from a reference femoral arterial catheter (PPVref) and the high-fidelity upper arm cuff (PPVcuff). The new device uses a semirigid conical shell. It incorporates a hydraulic sensor pad with a pressure transducer, leading to a tissue pressure-pulse contour with all characteristics of an arterial- pulse contour. The comparative analysis of the included measurements showed that PPVref and PPVcuff were closely correlated (r=0.92). The mean of the differences between PPVref and PPVcuff was 0.1 ± 2.0%, with 95% limits of agreement between -4.1% and 3.9%. To track absolute changes in PPV >2%, the concordance rate between the 2 methods was 93%. The new high-fidelity upper arm cuff method provided a clinically reliable estimate of PPV.

Early Mobility in Patients With Femoral Catheters

Early Mobility in Patients With Femoral Catheters

Venoarterial extracorporeal membrane oxygenation improves survival in a rat model of acute myocardial infarction.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used in high-risk acute myocardial infarction (AMI) patients with promising outcomes. However, the underlying molecular mechanisms remain unknown and a VA-ECMO animal model has not yet been established. The purpose of this study was to establish a VA-ECMO model in AMI rats and evaluate long-term cardiac function. We first established AMI in 20 Sprague-Dawley (SD) rats by ligating the left anterior descending coronary artery, while five rats underwent a thoracotomy to form the sham group. VA-ECMO was established after 30mins of AMI in 10 rats through the right jugular vein for venous drainage and right femoral artery for arterial infusion. Arterial blood pressure was monitored using a catheter in the left femoral artery, blood gas parameters were measured using a blood gas analyzer, while myocardial enzymes were detected using an ELISA Kit. Cardiac function was assessed through echocardiography on day 15. Masson staining and Western Blot were used for evaluating myocardial fibrosis, while histological injury was evaluated using hematoxylin and eosin staining. VA-ECMO support stabilized blood pressure, decreased the levels of myocardial enzymes including cTnI, cTnT, CK-MB, and was associated with a higher survival rate. In the long term, the VA-ECMO group showed improved cardiac function, significantly increased EF and FS but significantly decreased EDV and ESV compared to the AMI group. Furthermore, VA-ECMO significantly alleviated pathological damage and myocardial fibrosis. We established an economical, reliable, and reproducible VA-ECMO animal model in AMI rats, and demonstrated that VA-ECMO support prevents deteriorated cardiac function.

Cutaneous Mucormycosis Co-infection in a Patient with COVID-19

Mucormycosis is a life-threatening fungal infection usually seen in patients who are immunocompromised; however, to date, it has been rarely described in patients with COVID-19, although more recently, reports from India have described an increased incidence of these infections. This report describes a patient with COVID-19 who developed a fatal dermatologic mucormycosis infection. The patient, whose history included therapy for diffuse large B-cell lymphoma, had an incidental positive screening test for COVID-19 in February 2021 after exposure to a family member who had tested positive. They then presented to the emergency room a few weeks later exhibiting progressive dyspnoea and fever. A CT scan of the chest revealed ground glass opacities. They were intubated approximately 2 weeks later and their course was complicated by renal failure, for which continuous renal replacement therapy was started, and by refractory hypoxaemic and hypercapnic respiratory failure in which they were placed on venovenous extracorporeal membrane oxygenation. During their course in the intensive care unit (ICU), they developed a right thigh haematoma, thought to be related to the previous insertion of a femoral arterial pressure monitoring catheter. Several days before the patient’s death, the wound noted to be covered by a brown-black eschar was cultured on April 30 and returned positive for Rhizopus oryzae and Staphylococcus epidermidis on May 5. The patient was immediately started on liposomal amphotericin and posaconazole and taken urgently taken to the operating room for a radical debridement. Unfortunately, their post-operative course was characterised by fulminant haemodynamic collapse and multiple system organ failure, from which the patient died.

Postoperative Femoral Nerve Palsy and Meralgia Paresthetica after Gynecologic Oncologic Surgery.

Femoral nerve palsy and meralgia paresthetica following gynecologic cancer surgery are rare, but severe and long lasting. Here, we aimed to study their incidence, severity, possible risk factors and its time to remission. Between January 2008 and December 2017 976 gynecologic cancer patients were identified in our institutional database receiving surgery. Complete patient charts were reviewed retrospectively. Possible risk factors were analyzed by Fisher's exact test. 441 (45.18%) out 976 were treated for Ovarian cancer. In total 23 patients were identified with a postoperative neurological leg disorder. A femoral nerve palsy was present in 15 patients (1.5%) and a meralgia paresthetica in 8 patients (0.82%). Three patients showed both disorders. Duration of surgery (p = 0.0000), positioning during surgery (p = 0.0040), femoral artery catheter (p = 0.0051), prior chemotherapy (p = 0.0007), nicotine abuse (p = 0.00456) and prior polyneuropathy (p = 0.0181) showed a significant association with a postoperative femoral nerve palsy. Nicotine abuse (p = 0.0335) and prior chemotherapy (p = 0.0151) were significant for the development of a meralgia paresthetica. Long lasting surgery, patient positioning and femoral arterial catheter placement are risk factors for a postoperative femoral nerve palsy in gynecologic cancer surgery. Polyneuropathy, nicotine abuse, and prior chemotherapy are predisposing risk factors for a femoral nerve palsy and a meralgia paresthetica. A resolution of symptoms is the rule for both disorders within different time schedules.

Irisin Preserves Cardiac Performance and Insulin Sensitivity in Response to Hemorrhage.

Irisin, a cleaved product of the fibronectin type III domain containing protein-5, is produced in the muscle tissue, which plays an important role in modulating insulin resistance. However, it remains unknown if irisin provides a protective effect against the detrimental outcomes of hemorrhage. Hemorrhages were simulated in male CD-1 mice to achieve a mean arterial blood pressure of 35–45 mmHg, followed by resuscitation. Irisin (50 ng/kg) and the vehicle (saline) were administrated at the start of resuscitation. Cardiac function was assessed by echocardiography, and hemodynamics were measured through femoral artery catheterization. A glucose tolerance test was used to evaluate insulin sensitivity. An enzyme-linked immunosorbent assay was performed to detect inflammatory factors in the muscles and blood serum. Western blot was carried out to assess the irisin production in skeletal muscles. Histological analyses were used to determine tissue damage and active-caspase 3 apoptotic signals. The hemorrhage suppressed cardiac performance, as indicated by a reduced ejection fraction and fractional shortening, which was accompanied by enhanced insulin resistance and hyperinsulinemia. Furthermore, the hemorrhage resulted in a marked decrease in irisin and an increase in the production of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1). Additionally, the hemorrhage caused marked edema, inflammatory cell infiltration and active-caspase 3 positive signals in skeletal muscles and cardiac muscles. Irisin treatment led to a significant improvement in the cardiac function of animals exposed to a hemorrhage. In addition, irisin treatment improved insulin sensitivity, which is consistent with the suppressed inflammatory cytokine secretion elicited by hemorrhages. Furthermore, hemorrhage-induced tissue edema, inflammatory cell infiltration, and active-caspase 3 positive signaling were attenuated by irisin treatment. The results suggest that irisin protects against damage from a hemorrhage through the modulation of insulin sensitivity.

Long-Term Effectiveness and Safety of Femoropopliteal Drug-Coated Balloon Angioplasty : 5-Year Results of the Randomized Controlled EffPac Trial

PurposeThis study aimed to assess 5-year effectiveness and safety of femoropopliteal angioplasty with the Luminor® 35 drug-coated balloon (DCB).Materials and MethodsThe EffPac trial was a prospective, multicenter, randomized controlled trial that enrolled 171 patients of Rutherford category 2 to 4 with medium length femoropopliteal lesions. Patients were allocated 1:1 to either Luminor® 35 DCB angioplasty or plain old balloon angioplasty (POBA). Assessment at 5 years included primary patency, freedom from clinically driven target lesion revascularization (CD-TLR), clinical improvement, and target limb amputation. Long-term vital status was ascertained in 97.1% of the participants.ResultsKaplan–Meier curves at 5 years demonstrate a primary patency of 61.4% after DCB angioplasty and 53.5% after POBA (log-rank p = 0.040) with a decreasing difference throughout the observation period. Freedom from TLR was 82.1% and 73.7%, respectively (log-rank p = 0.050). Incidence of primary clinical improvement was similar between groups (61% DCB vs. 64% POBA, p = 0.94). Major target limb amputation was necessary in one POBA-group participant. Freedom from all-cause death at 5 years was 88.5% after DCB and 86.0% after POBA (log-rank p = 0.34).ConclusionsPrimary patency after femoropopliteal DCB angioplasty remained superior to POBA throughout 5 years, however, with decreasing difference. Clinical improvement, freedom from TLR, and all-cause mortality were similar between groups over the long term. (Effectiveness of Paclitaxel-Coated Luminor® Balloon Catheter Versus Uncoated Balloon Catheter in the Superficial Femoral Artery [EffPac]; NCT02540018).

Outcomes of Femoral Arterial Catheterisation in Neonates: A Retrospective Cohort Study.

Background: To review the outcome of all femoral arterial catheter (FAC) insertions in a single, large neonatal unit over a 12 year period, we will describe the incidence of harms arising from FAC insertion and to identify risk factors associated with ischaemic injury. Methods: Retrospective survey of data relating to all episodes of FAC insertion in a single neonatal intensive care unit over a 12 year period up to 2020. Results: 146 FACs were inserted into 139 babies with a median (interquartile range) gestation and birth weight of 27 (24 to 37) weeks and 1092 (682 to 2870) g. Impaired limb perfusion occurred in 32 (22%). This was transient and recovered with no injury in 26 of the 32. There was an increased risk of impaired limb perfusion in babies with lower weight at the time of insertion; from 5.7% in babies over 3000 g to 34.7% in babies under 1000 g (relative risk 6.1 (1.5 to 24.6)). Six babies (4%) had ischaemic injury. Risk factors for ischaemic injury included weight below 1000 g (four cases), pre-existing partial arterial obstruction (two cases), concerns about limb perfusion prior to FAC insertion (two cases) and a delay in removing the FAC after recognition of the poor perfusion (five cases). Two clinicians inserted 71 (50%) FACs and had no associated injuries. Conclusions: FAC can be used in neonates, although there is a risk of ischaemic injury, particularly in very small babies. Our data can be used to inform decisions about patient selection for this procedure.

Investigating effects of sodium beta-hydroxybutyrate on metabolism in placebo-controlled, bilaterally infused human leg with focus on skeletal muscle protein dynamics.

Systemic administration of beta‐hydroxybutyrate (BHB) decreases whole‐body protein oxidation and muscle protein breakdown in humans. We aimed to determine any direct effect of BHB on skeletal muscle protein turnover when administered locally in the femoral artery. Paired design with each subject being investigated on one single occasion with one leg being infused with BHB and the opposing leg acting as a control. We studied 10 healthy male volunteers once with bilateral femoral vein and artery catheters. One artery was perfused with saline (Placebo) and one with sodium‐BHB. Labelled phenylalanine and palmitate were used to assess local leg fluxes. Femoral vein concentrations of BHB were significantly higher in the intervention leg (3.4 (3.2, 3.6) mM) compared with the placebo‐controlled leg (1.9 (1.8, 2.1) mM) with a peak difference of 1.4 (1.1, 1.7) mM, p < 0.0005. Net loss of phenylalanine for BHB vs Placebo −6.7(−10.8, −2.7) nmol/min vs −8.7(−13.8, −3.7) nmol/min, p = 0.52. Palmitate flux and arterio‐venous difference of glucose did not differ between legs. Under these experimental conditions, we failed to observe the direct effects of BHB on skeletal muscle protein turnover. This may relate to a combination of high concentrations of BHB (close to 2 mM) imposed systemically by spillover leading to high BHB concentrations in the saline‐infused leg and a lack of major differences in concentration gradients between the two sides—implying that observations were made on the upper part of the dose–response curve for BHB and the relatively small number of subjects studied.

Pseudoshock: A Challenging Presentation of Bilateral Subclavian Artery Stenosis.

IntroductionSubclavian artery stenosis (SAS) is a manifestation of peripheral artery disease (PAD). Presentation varies, ranging from arm claudication and muscle fatigue to symptoms which reflect vertebrobasilar hypoperfusion, among which are syncope, ataxia and dysphagia. Although rare, severe bilateral SAS can exist and present as refractory hypotension. We describe a case of bilateral SAS masquerading as circulatory shock, or rather ‘pseudoshock’.Case DescriptionA 59-year-old female patient presented to the emergency department with complaints of dark stools. She was anaemic and hypotensive and therefore suspected to have an acute gastrointestinal bleed (GIB) with resultant haemorrhagic shock. Her hypotension was unresponsive to fluid resuscitation and blood transfusions. Bilateral upper extremity radial artery catheters confirmed low blood pressures. After her blood pressure failed to improve despite the addition of several vasopressors, a femoral artery catheter (FAC) was placed, which revealed significant hypertension discordant with the hypotension measured by the radial artery catheters. Review of CT angiography of the upper extremities revealed the presence of bilateral SAS which was deemed to be the aetiology of the falsely low blood pressure.DiscussionSAS should be suspected in patients with lower extremity PAD or a blood pressure (BP) differential of 15 mmHg or more between arms. When bilateral subclavian arteries are stenosed, this difference in BP may be concealed, making lower extremity BP measurements, as seen in non-invasive tests such as ankle brachial index (ABI) tests or through more invasive procedures such as FAC placement, critically important.ConclusionBilateral SAS may present as pseudo-hypotension. In cases of refractory shock of unclear aetiology, especially in patients with known PAD, a high index of suspicion is warranted for ‘pseudoshock’ secondary to severe vascular stenosis. Comparison of upper and lower extremity BP via invasive arterial catheters or non-invasive ABI tests can aid in the diagnosis of bilateral SAS.LEARNING POINTSBilateral subclavian artery stenosis (SAS) may present as pseudo-hypotension and shock of unclear aetiology.In patients with underlying peripheral arterial disease, pseudoshock should be considered in the differential diagnosis.Comparison of upper and lower extremity blood pressure via invasive arterial catheters or the non-invasive ankle brachial index (ABI) test has diagnostic value for bilateral SAS.Pseudoshock is managed via secondary prevention with antiplatelets and statins for asymptomatic patients, and revascularization for symptomatic patients.

P50: Save leg: using contralateral femoral inflow for distal perfusion catheter placed for Impella CP

Background: Leg ischemia is a possible complication of percutaneous left ventricular device (Impella CP TM) placement. To avoid leg ischemia in atrisk patients, a distal perfusion catheter (DPC) should be placed. The DPC can be connected to the wire-reaccess port of the Impella CP as an inflow to the DPC to perfuse the leg. However, the wire-reaccess port of the Impella was not designed to bypass arterial blood to the distal limb, but rather for wire passage. We introduced a passive distal perfusion system from the contralateral femoral artery to optimize blood flow to the distal limb. Methods: A 65 year-old female with dilated cardiomyopathy developed refractory ventricular tachycardia. She was taken to the catherization laboratory because of hemodynamic instability requiring high doses of vasopressors. By left heart catheterization, we noted normal coronary arteries with elevated left ventricular end-diastolic pressure (38 mm Hg) and a poor cardiac index. Thus, Impella CP was placed from the right groin to stabilize her hemodynamics. A DCP was placed on right distal femoral artery and connected to the wire-reaccess port of the Impella CP. The leg appeared perfused by DPC via reaccess port in the catherization laboratory; however, despite this as well as appropriate anticoagulation, the leg became ischemic (cold leg, low leg regional saturation) shortly after admission to the ICU, where a lack of flow in the DPC was confirmed. Results: An additional contralateral femoral arterial line was placed. The contralateral femoral arterial line was then connected to the DPC (figure), and the reaccess port of the Impella was capped. Shortly after placement of the new DPC system, the pulse was returned and leg saturation improved. Additionally, leg ischemia during Impella support did not reoccur. Conclusion: A DPC using the Impella CP reaccess port provided inadequate distal flow. When a DPC is indicated during femoral Impella CP use, the contralateral femoral artery should be chosen for inflow cannulation. Figure 1. Impella CP and distal perfusion catheter (DPC) in the right femoral artery. The arterial line in the left femoral artery is feeding DPC in the right femroal artery.

Agreements between mean arterial pressure from radial and femoral artery measurements in refractory shock patients

Radial and femoral artery catheterization is the most common procedure for monitoring patients with shock. However, a disagreement in mean arterial pressure (MAP) between the two sites has been reported. Hence, the aim of this study was to compare the MAP from the radial artery (MAPradial) with that of the femoral artery (MAPfemoral) in patients with refractory shock. A prospective study was conducted in the medical intensive care unit. The radial and femoral were simultaneously measured MAP in the patients every hour, for 24 h. In total, 706 paired data points were obtained from 32 patients. MAPradial strongly correlated with MAPfemoral (r = 0.89, p < 0.0001). However, overall MAPradial was significantly lower than MAPfemoral 7.6 mmHg. The bias between MAPradial and MAPfemoral was − 7.6 mmHg (95% limits of agreement (LOA), − 24.1 to 8.9). In the subgroup of patients with MAPradial < 65 mmHg, MAPradial moderately correlated with MAPfemoral (r = 0.63) and the bias was increased to − 13.0 mmHg (95% LOA, − 28.8 to 2.9). There were 414 (58.6%) measurements in which the MAP gradient between the two sites was > 5 mmHg. In conclusion, the radial artery significantly underestimated MAP compared with the femoral artery in patients with refractory shock.

Changes in Oxygen Consumption and Metabolomic Profiles in the Kidney of Sprague‐Dawley Rat fed a High‐Salt Diet

The metabolism of oxygen and substrates in the kidney under normal conditions and in salt‐sensitive hypertension is still not well understood. A novel method was developed to collect renal arteriovenous blood and urine from conscious freely moving rats, while measuring renal blood flow (RBF) and blood pressure (BP). As such, global renal O2 consumption and metabolic profiles can be studied in response to various stimuli such as changes in salt diet. We report here changes observed in male Sprague‐Dawley rats (SD; 10 wk age) before and after 21 days switching from a 0.4% NaCl (LS) diet to a 4.0% NaCl diet (HS). Rats were surgically instrumented with a renal ultrasonic artery flow probe (Transonic), a femoral arterial catheter, and a renal venous catheter and placed in a movement response caging system. After 7 days recovery, control levels of RBF and BP (24 hr/day) were obtained, and arterial and renal venous blood were sampled. Rats were then switched to the HS diet and blood sampled at days 7, 14 and 21 while RBF and BP were recorded continuously throughout the study. Blood O2 content was measured by radiometer immediately after blood collection and plasma samples frozen for global metabolomic analysis by the Jackson laboratory. The metabolomic analysis (Thermo Q‐Exactive Orbitrap coupled to a Vanquich UPLC system) was performed in 4 modes (C18 positive, C18 negative, HILIC positive and HILIC negative). Average 24 hr mean arterial pressure (MAP) of the SD rats increased slightly over the 21 days of the HS diet from 111 ± 2 to 119 ± 5 mmHg (p&lt;0.05; n=7). Average 24 hr RBF rose from 9.2 ± 0.6 to 11.7 + 0.6 ml/min (p&lt;0.05). O2 consumption increased significantly from 0.17 ± 0.03 to 0.26 ± 0.03 ml/min (p&lt;0.05) as did O2 extraction which increased from 10.8 ± 1.1 % to 15.0 ± 1.2 % by Day 21 of HS diet. Of a total 1205 named metabolites detected, we present here those that differed between arterial and renal venous blood by more than 2‐fold and significantly (p&lt;0.05; Benjamini‐Hochberg corrected). At the time of this report, in rats fed the LS diet, 33 compounds were found more abundant in arterial blood than in venous blood. 10 compounds were found more abundant in venous blood. The HS diet increased the arterial / venous ratio of some compounds progressively throughout the 21 days while others decreased. No evidence of anaerobic respiration was obtained with lactate, pyruvate, glutamate and TCA cycle related metabolites remaining unchanged throughout the study. Interestingly, some gut microbiome generated compounds were found to differentially altered by the HS diet. Despite no changes in arterial concentrations, a progressive reduction was observed in Triethylamine in the renal venous blood at each time point, while a progressive elevation was observed in Hexanoic acid. Venous levels of Cis‐4‐Decenedioic acid and Succinylacetone, known to be altered in some metabolic diseases were significantly increased by the HS diet. Urine measurements and cortical and outer medullary tissue measurements are currently under way which together with the RBF will enable calculation of metabolic fluxes of these various metabolites. We conclude that a high‐salt diet increases oxygen consumption and alters the metabolomic profiles of the kidney.

Difelikefalin, a peripherally restricted kappa opioid receptor agonist, evokes diuresis through a central kappa opioid receptor pathway

Kappa opioid receptor (KOR) agonists produce a variety of beneficial effects such as nonaddictive analgesia and diuresis, but their translation into the clinic has been hindered by central adverse effects (dysphoria). In clinical studies, difelikefalin, a KOR agonist recently FDA approved for treatment of pruritus in hemodialysis patients, was shown to be devoid of producing adverse CNS effects suggesting that this compound is peripherally restricted. This is of interest from a renal excretory perspective, since it would be predicted that difelikefalin would not produce diuresis, which is a classical centrally mediated response produced by KOR agonists. However, in preliminary studies in rats we have shown that IV administration of difelikefalin markedly increased urine output and decreased urinary sodium and potassium excretion similar to that produced by other KOR agonists. Therefore, we hypothesized that difelikefalin activates a central KOR pathway to cause diuresis. To test this hypothesis, Sprague‐Dawley rats were implanted with bladder, femoral artery, and femoral vein catheters and administered an isotonic saline infusion. To delineate the central and/or peripheral site of action of difelikefalin, renal excretory function was measured in rats pretreated centrally or peripherally with norBNI (KOR antagonist) or vehicle via an intracerebroventricular (ICV) cannula or IV catheter. Following stabilization, conscious rats were administered an IV bolus of difelikefalin (10 µg/kg) and urine output, mean arterial pressure (MAP), and heart rate (HR) were recorded for 90 minutes. The results demonstrated that ICV norBNI pretreatment significantly decreased the diuretic response to IV difelikefalin but had no effect on urinary sodium or potassium concentration (Table 1). In contrast, IV norBNI pretreatment prevented the diuresis to IV difelikefalin and increased urinary sodium/potassium concentration (Table 1). Notably, ICV and IV norBNI pretreatment abolished the difelikefalin‐induced decrease in MAP that was also seen in the vehicle pretreated groups. Together, these findings suggest that difelikefalin produces its diuretic and blood pressure effects through a central KOR pathway, while the sodium/potassium retaining effects of difelikefalin are mediated through peripheral KORs.