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Critical Care Explorations Jul 2024Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA... (Observational Study)
Observational Study Comparative Study
Microvascular Autoregulation in Skeletal Muscle Using Near-Infrared Spectroscopy and Derivation of Optimal Mean Arterial Pressure in the ICU: Pilot Study and Comparison With Cerebral Near-Infrared Spectroscopy.
IMPORTANCE
Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA has been studied in the brain to derive personalized hemodynamic targets after brain injury. The ability to measure MA in other organs is not known, which may inform individualized management during shock.
OBJECTIVES
This study determines the feasibility of measuring MA in skeletal muscle using near-infrared spectroscopy (NIRS) as a marker of tissue perfusion, the derivation of optimal mean arterial pressure (MAPopt), and comparison with indices from the brain.
DESIGN
Prospective observational study.
SETTING
Medical and surgical ICU in a tertiary academic hospital.
PARTICIPANTS
Adult critically ill patients requiring vasoactive support on the first day of ICU admission.
MAIN OUTCOMES AND MEASURES
Fifteen critically ill patients were enrolled. NIRS was applied simultaneously to skeletal muscle (brachioradialis) and brain (frontal cortex) while ABP was measured continuously via invasive catheter. MA correlation indices were calculated between ABP and NIRS from skeletal muscle total hemoglobin (MVx), muscle tissue saturation index (MOx), brain total hemoglobin (THx), and brain tissue saturation index (COx). Curve fitting algorithms derive the MAP with the lowest correlation index value, which is the MAPopt.
RESULTS
MAPopt values were successfully calculated for each correlation index for all patients and were frequently (77%) above 65 mm Hg. For all correlation indices, median time was substantially above impaired MA threshold (24.5-34.9%) and below target MAPopt (9.0-78.6%). Muscle and brain MAPopt show moderate correlation (MVx-THx r = 0.76, p < 0.001; MOx-COx r = 0.69, p = 0.005), with a median difference of -1.27 mm Hg (-9.85 to -0.18 mm Hg) and 0.05 mm Hg (-7.05 to 2.68 mm Hg).
CONCLUSIONS AND RELEVANCE
This study demonstrates, for the first time, the feasibility of calculating MA indices and MAPopt in skeletal muscle using NIRS. Future studies should explore the association between impaired skeletal muscle MA, ICU outcomes, and organ-specific differences in MA and MAPopt thresholds.
Topics: Humans; Spectroscopy, Near-Infrared; Muscle, Skeletal; Pilot Projects; Male; Prospective Studies; Female; Middle Aged; Intensive Care Units; Arterial Pressure; Homeostasis; Critical Illness; Aged; Adult; Microcirculation; Brain
PubMed: 38904977
DOI: 10.1097/CCE.0000000000001111 -
Kidney International Reports Jun 2024Persistent chronic hypotension affects 5-10% of dialysis patients. It seems to be reversible after receiving a functioning graft, but data regarding its influence on...
INTRODUCTION
Persistent chronic hypotension affects 5-10% of dialysis patients. It seems to be reversible after receiving a functioning graft, but data regarding its influence on transplant outcomes are scarce. We analyze the evolution of patients with chronic hypotension in dialysis who undergo kidney transplantation at our center.
METHODS
A retrospective observational study was conducted. Sixty-six patients with chronic hypotension (defined as systolic blood pressure ≤ 100 mm Hg at the time of transplantation) were identified. A control group of 66 non-hypotensive patients was assigned. The evolution of both groups was compared.
RESULTS
Hypotensive patients had higher rates of primary non-function (18.2% vs. 6.1%; = 0.03) mainly due to venous thrombosis of the allograft, worse renal function at the end of follow-up (eGFR of 35 mL/min/1.73 m vs 48 mL/min/1.73 m, = 0.001) but there was no statistical difference in graft survival after censoring for primary non-function. After multivariable adjustment, chronic hypotension remained an independent predictor factor for graft failure (adjusted HR of 2.85; 95% CI: 1.24-6.57; = 0.014). Use of vasoactive drugs and anticoagulation in hypotensive patients was associated with 7.1% of venous graft thrombosis compared to 17.3% in those with no intervention ( = 0.68). Receiving a functioning graft implied blood pressure normalization in patients with chronic hypotension.
CONCLUSION
Chronic hypotension in dialysis has a negative impact on short-term kidney transplant outcomes but a lower impact on long-term results. It is reversible after receiving a functioning graft. Identifying this subgroup of patients seems crucial to implement measures aimed at improving transplant results.
PubMed: 38899166
DOI: 10.1016/j.ekir.2024.03.012 -
Acute Medicine & Surgery 2024Strangulated intestinal obstruction is a life-threatening condition that should be considered as a differential diagnosis in children with shock. However, it has...
BACKGROUND
Strangulated intestinal obstruction is a life-threatening condition that should be considered as a differential diagnosis in children with shock. However, it has pitfalls in diagnosis and can lead to diagnostic errors.
CASE PRESENTATION
A 3-month-old male patient presented with a pale complexion lasting 2 h and abnormal crying. He was in shock with lactic acidosis, altered mental status, and slight abdominal distension. He required volume resuscitation, vasoactive agents, and transfusion. On Day 2, he had marked abdominal distension and acute kidney injury, which required continuous kidney replacement therapy. Contrast-enhanced computed tomography revealed extensive intestinal ischemia. It took 33.5 h from his arrival to the computed tomography, leading to operative management. The small intestine had entered a mesenteric hiatus, leading to ischemia. He was diagnosed with strangulated mesenteric hernia.
CONCLUSION
In this case, four pitfalls led to delayed diagnosis. Factors for diagnostic errors specific to strangulated intestinal obstruction and intensive care should be noted.
PubMed: 38894735
DOI: 10.1002/ams2.977 -
International Journal of Molecular... Jun 2024Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical...
Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical application, the combination of Lour. (AVL) and BBR can relieve it. However, the effective ingredients and molecular mechanism of AVL in relieving constipation are not clear. A small intestine propulsion experiment was conducted in constipated mice to screen active ingredients of AVL. We further confirmed the molecular mechanism of action of the active ingredient on BBR-induced constipation. Quercetin (QR) was found to be the effective ingredient of AVL in terms of relieving constipation. QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. The use of QR in combination with BBR has an adverse effect-reducing efficacy. The study provides new ideas and possibilities for the treatment of constipation induced by BBR.
Topics: Animals; Berberine; Quercetin; Constipation; Gastrointestinal Microbiome; Mice; Male; Disease Models, Animal; Motilin
PubMed: 38892414
DOI: 10.3390/ijms25116228 -
International Journal of Molecular... May 2024Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological... (Review)
Review
Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological factors contribute to its presentation and perpetuation, including macrocirculatory and microcirculatory changes, mitochondrial dysfunction, and metabolic reprogramming. Recovery from acute kidney injury (AKI) relies on the evolution towards adaptive mechanisms such as endothelial repair and tubular cell regeneration, while maladaptive repair increases the risk of progression to chronic kidney disease. Fundamental management strategies include early sepsis recognition and prompt treatment, through the administration of adequate antimicrobial agents, fluid resuscitation, and vasoactive agents as needed. In septic patients, organ-specific support is often required, particularly renal replacement therapy (RRT) in the setting of severe AKI, although ongoing debates persist regarding the ideal timing of initiation and dosing of RRT. A comprehensive approach integrating early recognition, targeted interventions, and close monitoring is essential to mitigate the burden of SA-AKI and improve patient outcomes in critical care settings.
Topics: Humans; Acute Kidney Injury; Sepsis; Renal Replacement Therapy; Critical Illness
PubMed: 38892111
DOI: 10.3390/ijms25115924 -
Animals : An Open Access Journal From... May 2024Crotalus snakebites induce various toxicological effects, encompassing neurological, myotoxic, and cytotoxic symptoms, with potentially fatal outcomes. Investigating...
A Comparative Analysis of the Cytotoxic and Vascular Activity Effects of Western Diamondback Rattlesnake () and Eastern Diamondback Rattlesnake () Venoms Using a Chick Embryo Model.
Crotalus snakebites induce various toxicological effects, encompassing neurological, myotoxic, and cytotoxic symptoms, with potentially fatal outcomes. Investigating venom toxicity is essential for public health, and developing new tools allows for these effects to be studied more comprehensively. The research goals include the elucidation of the physiological consequences of venom exposure and the assessment of toxicity using animal models. Chicken embryos serve as valuable models for assessing venom toxicity through the chick embryotoxicity screening test (CHEST) and the chick chorioallantoic membrane (CAM) assay, particularly useful for evaluating vascular impacts. venom application resulted in higher embryotoxicity and morphological abnormalities, such as Siamese twins. The CAM assay demonstrated the hemorrhagic effects of venom, varying with venom type and concentration. The irritant potential of both venom types was classified as slight or moderate depending on their concentration. Additionally, acetylcholinesterase (AChE) activity was performed to receive information about organ toxicity. The results show that both venoms induced changes in the whole embryo, heart, and liver weights, but the venom was identified as more toxic. Specific venom concentrations affected AChE activity in embryonic tissues. These findings underscore the embryotoxic and vasoactive properties of , providing valuable insights into their mechanisms of toxicity and potential applications in biomedicine.
PubMed: 38891681
DOI: 10.3390/ani14111634 -
Annals of Clinical and Translational... Jun 2024Migraine is a complex and disabling neurological disorder. Recent years have witnessed the development and emergence of novel treatments for the condition, namely those... (Review)
Review
OBJECTIVE
Migraine is a complex and disabling neurological disorder. Recent years have witnessed the development and emergence of novel treatments for the condition, namely those targeting calcitonin gene-related peptide (CGRP). However, there remains a substantial need for further treatments for those unresponsive to current therapies. Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) as a possible therapeutic strategy in the primary headache disorders has gained interest over recent years.
METHODS
This review will summarize what we know about PACAP to date: its expression, receptors, roles in migraine and cluster headache biology, insights gained from preclinical and clinical models of migraine, and therapeutic scope.
RESULTS
PACAP shares homology with vasoactive intestinal polypeptide (VIP) and is one of several vasoactive neuropeptides along with CGRP and VIP, which has been implicated in migraine neurobiology. PACAP is widely expressed in areas of interest in migraine pathophysiology, such as the thalamus, trigeminal nucleus caudalis, and sphenopalatine ganglion. Preclinical evidence suggests a role for PACAP in trigeminovascular sensitization, while clinical evidence shows ictal release of PACAP in migraine and intravenous infusion of PACAP triggering attacks in susceptible individuals. PACAP leads to dural vasodilatation and secondary central phenomena via its binding to different G-protein-coupled receptors, and intracellular downstream effects through cyclic adenosine monophosphate (cAMP) and phosphokinase C (PKC). Targeting PACAP as a therapeutic strategy in headache has been explored using monoclonal antibodies developed against PACAP and against the PAC1 receptor, with initial positive results.
INTERPRETATION
Future clinical trials hold considerable promise for a new therapeutic approach using PACAP-targeted therapies in both migraine and cluster headache.
PubMed: 38887982
DOI: 10.1002/acn3.52119 -
Frontiers in Pediatrics 2024The primary aim of this study was to compare non-invasive blood pressure (NIBP) measurement using the automated oscillometric method with invasive blood pressure (IBP)...
Comparison of invasive blood pressure monitoring vs. non-invasive blood pressure monitoring in critically ill children receiving vasoactive agents-a prospective observational study.
OBJECTIVE
The primary aim of this study was to compare non-invasive blood pressure (NIBP) measurement using the automated oscillometric method with invasive blood pressure (IBP) measurement using peripheral arterial line insertion in critically ill children receiving vasoactive agents.
DESIGN
Single-centre, prospective cohort study.
SETTING
Tertiary care 15 bedded Pediatric ICU in Urban Indian city.
SUBJECTS
All critically ill children between the ages of 1 month to 16 years with shock on vasoactive medications and with IBP monitoring.
RESULTS
Forty children with 1,072 paired BP measurements were incorporated in the final analysis. Among all normotensive children (Total number of paired measurements = 623) receiving vasoactive agents, Bland-Altman analysis revealed an acceptable agreement between Invasive mean blood pressure (MBP) and non-invasive MBP with a bias of -2.10 mmHg (SD 11.35). The 95% limits of agreement were from -24.34 to 20.14 mmHg. In children with hypotension (Total number of paired measurements = 449), Bland-Altman analysis showed disagreement between Invasive MBP and non-invasive MBP i.e., a bias of -8.44 mmHg (SD 9.62). The 95% limits of agreement were from -27.29 to 10.41 mmHg.
CONCLUSION
A limited agreement exists between invasive blood pressure (IBP) and non-invasive blood pressure (NIBP) measurements in critically ill children requiring vasoactive agents. This discrepancy can lead to either an underestimation or an overestimation of blood pressure. While NIBP can serve as a screening tool for hemodynamically stable children, those who are hemodynamically unstable and necessitate the initiation of vasoactive agents should undergo IBP monitoring.
PubMed: 38887566
DOI: 10.3389/fped.2024.1376327 -
MedRxiv : the Preprint Server For... Jun 2024Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the...
Cerebrovascular reactivity (CVR) reflects the ability of blood vessels to dilate or constrict in response to a vasoactive stimulus, and allows researchers to assess the brain's vascular health. Individuals with spinal cord injury (SCI) are at an increased risk for autonomic dysfunction in addition to cognitive impairments, which have been linked to a decline in CVR; however, there is currently a lack of brain-imaging studies that investigate how CVR is altered after SCI. In this study, we used a breath-holding hypercapnic stimulus and functional near-infrared spectroscopy (fNIRS) to investigate CVR alterations in individuals with SCI (n = 20, 14M, 6F, mean age = 46.3 ± 10.2 years) as compared to age- and sex-matched able-bodied (AB) controls (n = 25, 19M, 6F, mean age = 43.2 ± 12.28 years). CVR was evaluated by its amplitude and delay components separately by using principal component analysis and cross-correlation analysis, respectively. We observed significantly delayed CVR in the right inferior parietal lobe in individuals with SCI compared to AB controls (linear mixed-effects model, fixed-effects estimate = 6.565, Satterthwaite's t-test, t = 2.663, p = 0.008), while the amplitude of CVR was not significantly different. The average CVR delay in the SCI group in the right inferior parietal lobe was 14.21 s (sd: 6.60 s), and for the AB group, the average delay in the right inferior parietal lobe was 7.08 s (sd: 7.39 s). CVR delays were also associated with the duration since injury in individuals with SCI, in which a longer duration since injury was associated with a shortened delay in CVR in the right inferior parietal region (Pearson's r-correlation, r = -0.59, p = 0.04). This study shows that fNIRS can be used to quantify changes in CVR in individuals with SCI, and may be further used in rehabilitative settings to monitor the cerebrovascular health of individuals with SCI.
PubMed: 38883754
DOI: 10.1101/2024.06.03.24307819 -
MedComm Jul 2024Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor...
Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro]-NPY and [Leu, Pro]-NPY, mainly acting on YR, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through YR. However, the recognition mechanisms of YR and YR with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled YR and YR in complexes with NPY, as well as YR bound to a selective agonist [Leu, Pro]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of YR evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.
PubMed: 38882210
DOI: 10.1002/mco2.565