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AACN Advanced Critical Care Dec 2023Measuring hemodynamic parameters has become safer and more precise than in the past. Accurately monitoring and evaluating the effectiveness of fluid, inotrope, and...
Measuring hemodynamic parameters has become safer and more precise than in the past. Accurately monitoring and evaluating the effectiveness of fluid, inotrope, and vasoactive medication administration can improve patient outcomes. Arbitrary fluid administration without stroke volume measurement can be detrimental to patient outcomes. Early detection and prompt treatment of shock states is essential to combat deleterious effects on critically ill patients. In addition to measuring traditional hemodynamic variables, the use of advanced variables such as hypotension prediction index, dynamic arterial elastance, and systolic slope can improve the precision of treat ment for critically ill patients. Using predictive analytics can help the bedside critical care nurse provide patient care that is proactive rather than reactive.
Topics: Humans; Hemodynamic Monitoring; Critical Illness; Hemodynamics; Shock; Critical Care; Monitoring, Physiologic
PubMed: 38033220
DOI: 10.4037/aacnacc2023903 -
Frontiers in Physiology 2023The corpus luteum is a transient ovarian endocrine gland that produces the progesterone necessary for the establishment and maintenance of pregnancy. The formation and... (Review)
Review
The corpus luteum is a transient ovarian endocrine gland that produces the progesterone necessary for the establishment and maintenance of pregnancy. The formation and function of this gland involves angiogenesis, establishing the tissue with a robust blood flow and vast microvasculature required to support production of progesterone. Every steroidogenic cell within the corpus luteum is in direct contact with a capillary, and disruption of angiogenesis impairs luteal development and function. At the end of a reproductive cycle, the corpus luteum ceases progesterone production and undergoes rapid structural regression into a nonfunctional corpus albicans in a process initiated and exacerbated by the luteolysin prostaglandin F2α (PGF2α). Structural regression is accompanied by complete regression of the luteal microvasculature in which endothelial cells die and are sloughed off into capillaries and lymphatic vessels. During luteal regression, changes in nitric oxide transiently increase blood flow, followed by a reduction in blood flow and progesterone secretion. Early luteal regression is marked by an increased production of cytokines and chemokines and influx of immune cells. Microvascular endothelial cells are sensitive to released factors during luteolysis, including thrombospondin, endothelin, and cytokines like tumor necrosis factor alpha (TNF) and transforming growth factor β 1 (TGFB1). Although PGF2α is known to be a vasoconstrictor, endothelial cells do not express receptors for PGF2α, therefore it is believed that the angioregression occurring during luteolysis is mediated by factors downstream of PGF2α signaling. Yet, the exact mechanisms responsible for angioregression in the corpus luteum remain unknown. This review describes the current knowledge on angioregression of the corpus luteum and the roles of vasoactive factors released during luteolysis on luteal vasculature and endothelial cells of the microvasculature.
PubMed: 37841308
DOI: 10.3389/fphys.2023.1254943 -
American Journal of Obstetrics and... Mar 2024Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to...
BACKGROUND
Preeclampsia is characterized by maternal endothelial activation and placental dysfunction. Imbalance in maternal angiogenic and vasoactive factors has been linked to the pathophysiology. The contribution of the placenta as a source of these factors remains unclear. Furthermore, little is known about fetal angiogenic and vasoactive proteins and the relation between maternal and fetal levels.
OBJECTIVE
We describe placental growth factor, soluble Fms-like tyrosine kinase 1, soluble endoglin, and endothelin 1-3 in 5 vessels in healthy pregnancies, early- and late-onset preeclampsia. Specifically, we aimed to (1) compare protein abundance in vessels at the maternal-fetal interface between early- and late-onset preeclampsia, and healthy pregnancies, (2) describe placental uptake and release of proteins, and (3) describe protein abundance in the maternal vs fetal circulations.
STUDY DESIGN
Samples were collected from the maternal radial artery, uterine vein and antecubital vein, and fetal umbilical vein and artery in 75 healthy and 37 preeclamptic mother-fetus pairs (including 19 early-onset preeclampsia and 18 late-onset preeclampsia), during scheduled cesarean delivery. This method allows estimation of placental release and uptake of proteins by calculation of venoarterial differences on each side of the placenta. The microarray-based SomaScan assay quantified the proteins.
RESULTS
The abundance of soluble Fms-like tyrosine kinase 1 and endothelin 1 was higher in the maternal vessels in preeclampsia than in healthy pregnancies, with the highest abundance in early-onset preeclampsia. Placental growth factor was lower in the maternal vessels in early-onset preeclampsia than in both healthy and late-onset preeclampsia. Maternal endothelin 2 was higher in preeclampsia, with late-onset preeclampsia having the highest abundance. Our model confirmed placental release of placental growth factor and soluble Fms-like tyrosine kinase 1 to the maternal circulation in all groups. The placenta released soluble Fms-like tyrosine kinase 1 into the fetal circulation in healthy and late-onset preeclampsia pregnancies. Fetal endothelin 1 and soluble Fms-like tyrosine kinase 1 were higher in early-onset preeclampsia, whereas soluble endoglin and endothelin 3 were lower in both preeclampsia groups than healthy controls. Across groups, abundances of placental growth factor, soluble Fms-like tyrosine kinase 1, and endothelin 3 were higher in the maternal artery than the fetal umbilical vein, whereas endothelin 2 was lower.
CONCLUSION
An increasing abundance of maternal soluble Fms-like tyrosine kinase 1 and endothelin 1 across the groups healthy, late-onset preeclampsia and early-onset combined with a positive correlation may suggest that these proteins are associated with the pathophysiology and severity of the disease. Elevated endothelin 1 in the fetal circulation in early-onset preeclampsia represents a novel finding. The long-term effects of altered protein abundance in preeclampsia on fetal development and health remain unknown. Further investigation of these proteins' involvement in the pathophysiology and as treatment targets is warranted.
PubMed: 38494070
DOI: 10.1016/j.ajog.2024.03.012 -
The Journal of Sexual Medicine Aug 2023Based on previous studies of vaginal lubrication as well as our own previously reported interview study of women who self-reported methamphetamine (meth)-induced vaginal...
BACKGROUND
Based on previous studies of vaginal lubrication as well as our own previously reported interview study of women who self-reported methamphetamine (meth)-induced vaginal lubrication, in the current study we sought to determine the potential dose-response relationship leading to meth-induced vaginal lubrication. We also developed an animal model to study the reported effects and examine potential mechanisms mediating this phenomenon.
AIM
We sought to characterize the effects of meth on vaginal lubrication in an animal model with the aim of providing a potential framework for new mechanisms that incorporate novel therapeutic agents for the treatment of vaginal dryness.
METHODS
Vaginal lubrication was measured via insertion of a preweighed, cotton-tipped swab into the vaginal canal of anesthetized rats following treatment with various doses of intravenous (IV) meth, up to 0.96 mg/kg, and after additional pharmacological manipulations, including administration of a nitric oxide synthase inhibitor and an estrogen receptor antagonist. Plasma signaling molecules, including estradiol, progesterone, testosterone, nitric oxide, and vasoactive intestinal polypeptide, were measured immediately before and at 9 time points after IV meth administration. Blood was collected via a previously implanted chronic indwelling jugular catheter and analyzed by use of commercially available kits per the manufacturer's instructions.
OUTCOMES
Outcomes for this study include the measurement of vaginal lubrication in anesthetized rats following various pharmacological manipulations and plasma levels of various signaling molecules.
RESULTS
Meth dose-dependently increased vaginal lubrication in anesthetized female rats. Meth significantly increased plasma levels compared to baseline of estradiol (2 and 15 minutes after meth infusion) as well as progesterone, testosterone, and nitric oxide (10 minutes after meth infusion). Also, vasoactive intestinal polypeptide decreased significantly compared to baseline for 45 minutes following meth infusion. Our data further suggest that nitric oxide, but not estradiol, is critical in the production of vaginal secretions in response to meth.
CLINICAL IMPLICATIONS
This study has far-reaching implications for women who are suffering from vaginal dryness and for whom estrogen therapy is unsuccessful, as the investigation has demonstrated that meth presents a novel mechanism for producing vaginal lubrication that can be targeted pharmacologically.
STRENGTHS AND LIMITATIONS
This study is, to our knowledge, the first performed to measure the physiological sexual effects of meth in an animal model. Animals were anesthetized when they were administered meth. In an ideal situation, animals would be self-administering the drug to recapitulate better the contingent nature of drug taking; however, this method was not feasible for the study reported here.
CONCLUSION
Methamphetamine increases vaginal lubrication in female rats through a nitric oxide-dependent mechanism.
Topics: Rats; Female; Animals; Methamphetamine; Nitric Oxide; Vasoactive Intestinal Peptide; Progesterone; Lubrication; Self Administration
PubMed: 37291060
DOI: 10.1093/jsxmed/qdad076 -
Pharmacotherapy Nov 2023There are several clinical practice guidelines concerning the use of fluid and vasoactive drug therapies in critically ill adult patients, but the recommendations in... (Review)
Review
There are several clinical practice guidelines concerning the use of fluid and vasoactive drug therapies in critically ill adult patients, but the recommendations in these guidelines are often based on low-quality evidence. Further, some were compiled prior to the publication of landmark clinical trials, particularly in the comparison of balanced crystalloid and normal saline. An important consideration in the treatment of critically ill patients is the application of precision medicine to provide the most effective care to groups of patients most likely to benefit from the therapy. Although not currently widely integrated into these practice guidelines, the utility of precision medicine in critical illness is a recognized research priority for fluid and vasoactive therapy management. The purpose of this narrative review was to illustrate the evaluation and challenges of providing precision fluid and vasoactive therapies to adult critically ill patients. The review includes a discussion of important investigations published after the release of currently available clinical practice guidelines to provide insight into how recommendations and research priorities may change future guidelines and bedside care for critically ill patients.
Topics: Adult; Humans; Fluid Therapy; Critical Illness; Crystalloid Solutions
PubMed: 36606689
DOI: 10.1002/phar.2763 -
Nature Communications Jul 2023Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of cortical responses to sound. The precise...
Peripheral sensory organ damage leads to compensatory cortical plasticity that is associated with a remarkable recovery of cortical responses to sound. The precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons remain unknown. After noise trauma and persistent peripheral deficits, we found recovered sound-evoked activity in mouse A1 excitatory principal neurons (PNs), parvalbumin- and vasoactive intestinal peptide-expressing neurons (PVs and VIPs), but reduced activity in somatostatin-expressing neurons (SOMs). This cell-type-specific recovery was also associated with cell-type-specific intrinsic plasticity. These findings, along with our computational modelling results, are consistent with the notion that PV plasticity contributes to PN stability, SOM plasticity allows for increased PN and PV activity, and VIP plasticity enables PN and PV recovery by inhibiting SOMs.
Topics: Mice; Animals; Auditory Cortex; Interneurons; Neurons; Vasoactive Intestinal Peptide; Sound; Parvalbumins
PubMed: 37443148
DOI: 10.1038/s41467-023-39732-7 -
Endocrinology Aug 2023In this review, we provide the status of research on vasoactive intestinal peptide (VIP) and oxytocin, typical C-terminal α-amidated peptide hormones, including their... (Review)
Review
In this review, we provide the status of research on vasoactive intestinal peptide (VIP) and oxytocin, typical C-terminal α-amidated peptide hormones, including their precursor protein structures, processing and C-terminal α-amidation, and the recently identified mechanisms of regulation of oxytocin secretion and its transportation through the blood brain barrier. More than half of neural and endocrine peptides, such as VIP and oxytocin, have the α-amide structure at their C-terminus, which is essential for biological activities. We have studied the synthesis and function of C-terminal α-amidated peptides, including VIP and oxytocin, since the 1980s. Human VIP mRNA encoded not only VIP but also another related C-terminal α-amidated peptide, PHM-27 (peptide having amino-terminal histidine, carboxy-terminal methionine amide, and 27 amino acid residues). The human VIP/PHM-27 gene is composed of 7 exons and regulated synergistically by cyclic AMP and protein kinase C pathways. VIP has an essential role in glycemic control using transgenic mouse technology. The peptide C-terminal α-amidation proceeded through a 2-step mechanism catalyzed by 2 different enzymes encoded in a single mRNA. In the oxytocin secretion from the hypothalamus/the posterior pituitary, the CD38-cyclic ADP-ribose signal system, which was first established in the insulin secretion from pancreatic β cells of the islets of Langerhans, was found to be essential. A possible mechanism involving RAGE (receptor for advanced glycation end-products) of the oxytocin transportation from the blood stream into the brain through the blood-brain barrier has also been suggested.
Topics: Mice; Humans; Animals; Vasoactive Intestinal Peptide; Oxytocin; Peptide PHI; Receptor for Advanced Glycation End Products; Amides; Mice, Transgenic
PubMed: 37548257
DOI: 10.1210/endocr/bqad121 -
Transplantation Apr 2024We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the "liver transplantation" and "vasoactive drug" domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions' mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.
Topics: Adult; Humans; Liver Transplantation; Blood Loss, Surgical; Network Meta-Analysis; Vasoconstrictor Agents; Vasodilator Agents; Acute Kidney Injury
PubMed: 37525360
DOI: 10.1097/TP.0000000000004744 -
Molecular Neurodegeneration Oct 2023Cerebral amyloid angiopathy (CAA) is a devastating condition common in patients with Alzheimer's disease but also observed in the general population. Vascular oxidative...
BACKGROUND
Cerebral amyloid angiopathy (CAA) is a devastating condition common in patients with Alzheimer's disease but also observed in the general population. Vascular oxidative stress and neurovascular dysfunction have been implicated in CAA but the cellular source of reactive oxygen species (ROS) and related signaling mechanisms remain unclear. We tested the hypothesis that brain border-associated macrophages (BAM), yolk sac-derived myeloid cells closely apposed to parenchymal and leptomeningeal blood vessels, are the source of radicals through the Aβ-binding innate immunity receptor CD36, leading to neurovascular dysfunction, CAA, and cognitive impairment.
METHODS
Tg2576 mice and WT littermates were transplanted with CD36 or CD36 bone marrow at 12-month of age and tested at 15 months. This approach enables the repopulation of perivascular and leptomeningeal compartments with CD36 BAM. Neurovascular function was tested in anesthetized mice equipped with a cranial window in which cerebral blood flow was monitored by laser-Doppler flowmetry. Amyloid pathology and cognitive function were also examined.
RESULTS
The increase in blood flow evoked by whisker stimulation (functional hyperemia) or by endothelial and smooth muscle vasoactivity was markedly attenuated in WT → Tg2576 chimeras but was fully restored in CD36 → Tg2576 chimeras, in which BAM ROS production was suppressed. CAA-associated Aβ, but not Aβ, was reduced in CD36 → Tg2576 chimeras. Similarly, CAA, but not parenchymal plaques, was reduced in CD36 → Tg2576 chimeras. These beneficial vascular effects were associated with cognitive improvement. Finally, CD36 mice were able to more efficiently clear exogenous Aβ injected into the neocortex or the striatum.
CONCLUSIONS
CD36 deletion in BAM suppresses ROS production and rescues the neurovascular dysfunction and damage induced by Aβ. CD36 deletion in BAM also reduced brain Aβ and ameliorated CAA without affecting parenchyma plaques. Lack of CD36 enhanced the vascular clearance of exogenous Aβ. Restoration of neurovascular function and attenuation of CAA resulted in a near complete rescue of cognitive function. Collectively, these data implicate brain BAM in the pathogenesis of CAA and raise the possibility that targeting BAM CD36 is beneficial in CAA and other conditions associated with vascular Aβ deposition and damage.
Topics: Humans; Mice; Animals; Reactive Oxygen Species; Mice, Transgenic; Cerebral Amyloid Angiopathy; Amyloid beta-Peptides; Alzheimer Disease; Brain; Macrophages; Oxidative Stress; Cognitive Dysfunction
PubMed: 37789345
DOI: 10.1186/s13024-023-00660-1