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Anesthesia and Pain Medicine Apr 2024Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following... (Review)
Review
Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following spinal anesthesia is generally defined as a blood pressure of 80-90% below the baseline value. Various strategies have been implemented to reduce the incidence of spinal anesthesia-induced hypotension. The administration of vasopressors is a crucial method for preventing and treating hypotension. In the past decade, phenylephrine, a primarily alpha-adrenergic agonist, has been the preferred vasopressor for cesarean sections. Recently, norepinephrine, a potent alpha-agonist with modest beta-agonist activity, has gained popularity owing to its advantages over phenylephrine. Vasopressors can be administered via a bolus or continuous infusion. Although administering boluses alone is simpler in a clinical setting, continuous prophylactic infusion initiated immediately after spinal anesthesia is more effective in reducing the incidence of hypotension. Tailoring the infusion dose based on the patient's body weight and adjusting the rate in response to blood pressure changes, in addition to using a prophylactic or rescue bolus, helps reduce blood pressure variability during cesarean sections under spinal anesthesia until neonatal delivery.
PubMed: 38725163
DOI: 10.17085/apm.24037 -
Science Advances May 2024Metabolic reprogramming is critical in the onset of pressure overload-induced cardiac remodeling. Our study reveals that proline dehydrogenase (PRODH), the key enzyme in...
Metabolic reprogramming is critical in the onset of pressure overload-induced cardiac remodeling. Our study reveals that proline dehydrogenase (PRODH), the key enzyme in proline metabolism, reprograms cardiomyocyte metabolism to protect against cardiac remodeling. We induced cardiac remodeling using transverse aortic constriction (TAC) in both cardiac-specific PRODH knockout and overexpression mice. Our results indicate that PRODH expression is suppressed after TAC. Cardiac-specific PRODH knockout mice exhibited worsened cardiac dysfunction, while mice with PRODH overexpression demonstrated a protective effect. In addition, we simulated cardiomyocyte hypertrophy in vitro using neonatal rat ventricular myocytes treated with phenylephrine. Through RNA sequencing, metabolomics, and metabolic flux analysis, we elucidated that PRODH overexpression in cardiomyocytes redirects proline catabolism to replenish tricarboxylic acid cycle intermediates, enhance energy production, and restore glutathione redox balance. Our findings suggest PRODH as a modulator of cardiac bioenergetics and redox homeostasis during cardiac remodeling induced by pressure overload. This highlights the potential of PRODH as a therapeutic target for cardiac remodeling.
Topics: Animals; Ventricular Remodeling; Proline; Myocytes, Cardiac; Mice; Mice, Knockout; Rats; Proline Oxidase; Energy Metabolism; Myocardium; Cardiomegaly; Disease Models, Animal; Oxidation-Reduction; Male; Metabolic Reprogramming
PubMed: 38718121
DOI: 10.1126/sciadv.adl3549 -
Journal of Biomedical Optics Jun 2024Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major...
SIGNIFICANCE
Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS).
AIM
This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery.
APPROACH
The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts.
RESULTS
In the first protocol ( years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients ( years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed.
CONCLUSIONS
The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.
Topics: Humans; Spectroscopy, Near-Infrared; Female; Male; Adult; Cerebrovascular Circulation; Hemodynamics; Oximetry; Oxygen; Brain; Equipment Design
PubMed: 38707651
DOI: 10.1117/1.JBO.29.S3.S33302 -
Drug Design, Development and Therapy 2024Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the... (Randomized Controlled Trial)
Randomized Controlled Trial
Dose-Response Study of Phenylephrine for Preventing Spinal-Induced Hypotension During Cesarean Delivery with Combined Spinal-Epidural Anesthesia Under the Effect of Prophylactic Intravenous Ondansetron.
BACKGROUND
Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the exact dose response of phenylephrine in combination with prophylactic ondansetron for preventing SIH is unknown. Therefore, this study aimed to determine the dose-response of phenylephrine to prevent SIH in cesarean delivery when 4 mg of ondansetron was used as a preventive method.
METHODS
A total of 80 parturients were enrolled and divided randomly into four groups (n = 20 in each group) who received either 0.2, 0.3, 0.4, or 0.5 μg/kg/min of prophylactic phenylephrine. Ten minutes before the initiation of spinal induction, 4 mg prophylactic ondansetron was administered. The effective dose of prophylactic phenylephrine was defined as the dose required to prevent hypotension after the period of intrathecal injection and up to neonatal delivery. The ED50 and ED90 of prophylactic phenylephrine and 95% confidence intervals (95% CI) were calculated using probit analysis.
RESULTS
The ED50 and ED90 for prophylactic phenylephrine to prevent SIH were 0.25 (95% CI, 0.15 to 0.30), and 0.45 (95% CI, 0.39 to 0.59) μg/kg/min, respectively. No significant differences were observed in the side effects and neonatal outcomes between the four groups.
CONCLUSION
The administration of 4 mg of prophylactic ondansetron was associated with an ED50 of 0.25 (95% CI, 0.15~0.30) and ED90 of 0.45 (95% CI, 0.39~0.59) μg/kg/min for phenylephrine to prevent SIH.
Topics: Adult; Female; Humans; Pregnancy; Anesthesia, Epidural; Anesthesia, Spinal; Cesarean Section; Dose-Response Relationship, Drug; Hypotension; Ondansetron; Phenylephrine
PubMed: 38707613
DOI: 10.2147/DDDT.S452983 -
Arquivos Brasileiros de Cardiologia Apr 2024Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role...
BACKGROUND
Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling.
OBJECTIVE
Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms.
METHODS
Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%.
RESULTS
T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates.
CONCLUSION
T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.
Topics: Animals; Vasodilation; Male; Triiodothyronine; Rats, Wistar; Oxidation-Reduction; Reactive Oxygen Species; Oxidative Stress; Phenylephrine; Endothelium, Vascular; Rats; Reproducibility of Results; Vasoconstrictor Agents; Aorta, Thoracic; In Vitro Techniques; Vasoconstriction
PubMed: 38695407
DOI: 10.36660/abc.20230236 -
Heliyon May 2024Hypotension is one of the most common and dangerous complications following combined spinal epidural anesthesia during elective cesarean delivery. Many methods are used...
BACKGROUD
Hypotension is one of the most common and dangerous complications following combined spinal epidural anesthesia during elective cesarean delivery. Many methods are used to prevent or treat the hypotension with pharmacological or non-pharmacological measures. Our aim was to assess left-lateral position and phenylephrine prophylactic treatment for the prevention or treatment of maternal hypotension.
METHODS
A total of 127 pregnant women were enrolled to be analyzed. The primary outcome measure was the incidence of maternal hypotension and secondary outcome measures included maternal demographic characteristics, anesthesia-to-incision time interval, birthweight and Apgar scores.
RESULTS
The incidence of hypotension was 65.4 % in sequential reactive treatment and only 11.3 % achieved complete anesis after left-lateral position, significantly higher than 17.4 % in left-lateral position combined phenylephrine prophylactic treatment ( < 0.001). The increasing in gestational age may decrease the hypotension risk ( < 0.001). There were no significantly differences with maternal age, gravidity, parity, BMI before pregnancy, BMI before cesarean section, anesthesia-to-incision time interval, birthweight and Apgar scores ( > 0.05). The univariate logistic regression analysis revealed a significant association between treatment and hypotension (OR 0.11, 95 % CI 0.05-0.27). After adjusting for confounding variables, the risk of hypotension was decreased in subjects with treatment (OR 0.1, 95 % CI 0.04-0.25; OR 0.15, 95 % CI 0.05-0.43; OR 0.16, 95 % CI 0.05-0.46). The results of stratified and interaction analyses of the association between treatment revealed no interactive role from maternal age, gravidity and BMI before cesarean section ( > 0.05).
CONCLUSIONS
Single use of left-lateral position had limited effective and left-lateral position combined prophylactic phenylephrine used may be much better to prevent or treat hypetension, but larger studies with more robust data are needed to confirm these findings.
PubMed: 38694024
DOI: 10.1016/j.heliyon.2024.e30019 -
International Journal of Molecular... Apr 2024(L.) Cusson, a member of the family, is rich in coumarins, such as imperatorin and osthole. fruit (CM) has a broad range of therapeutic potential that can be used in...
(L.) Cusson, a member of the family, is rich in coumarins, such as imperatorin and osthole. fruit (CM) has a broad range of therapeutic potential that can be used in anti-bacterial, anti-cancer, and sexual dysfunction treatments. However, its efficacy in lowering blood pressure through vasodilation remains unknown. This study aimed to assess the potential therapeutic effect of CM 50% ethanol extract (CME) on hypertension and the mechanism of its vasorelaxant effect. CME (1-30 µg/mL) showed a concentration-dependent vasorelaxation on constricted aortic rings in Sprague Dawley rats induced by phenylephrine via an endothelium-independent mechanism. The vasorelaxant effect of CME was inhibited by blockers of voltage-dependent and Ca-activated K channels. Additionally, CME inhibited the vascular contraction induced by angiotensin II and CaCl. The main active compounds of CM, i.e., imperatorin (3-300 µM) and osthole (1-100 µM), showed a concentration-dependent vasorelaxation effect, with half-maximal effective concentration values of 9.14 ± 0.06 and 5.98 ± 0.06 µM, respectively. Orally administered CME significantly reduced the blood pressure of spontaneously hypertensive rats. Our research shows that CME is a promising treatment option for hypertension. However, further studies are required to fully elucidate its therapeutic potential.
Topics: Animals; Cnidium; Plant Extracts; Blood Pressure; Rats, Sprague-Dawley; Rats; Fruit; Vasodilator Agents; Male; Rats, Inbred SHR; Antihypertensive Agents; Ethanol; Furocoumarins; Hypertension; Vasodilation; Coumarins
PubMed: 38673809
DOI: 10.3390/ijms25084223 -
Journal of Clinical Medicine Apr 2024: Sulodexide (SDX) is a drug known for restoring the glycocalyx, thereby offering endothelial protection and regulating permeability. Additionally, it has antithrombotic...
: Sulodexide (SDX) is a drug known for restoring the glycocalyx, thereby offering endothelial protection and regulating permeability. Additionally, it has antithrombotic and anti-inflammatory properties and has shown arterial vasodilatory effects. Endothelial cells play a crucial role in maintaining homeostasis, with their dysfunction being a key contributor to loss in vasodilatory response, especially in arterial pathologies. The aim of this study was to investigate the effects of SDX on stimulated vascular tonus in human arterial samples and to assess the function of the endothelial layer as a source of nitric oxide (NO). : A total of 16 internal mammary artery remnants from coronary artery bypass graft surgeries were dissected into endothelium-intact and endothelium-denuded groups (n = 8 each). The arterial rings were equilibrated under tension, with their basal tonus recorded before and after phenylephrine stimulation. SDX's impact on arterial contraction was assessed through cumulative dose-response curves. NO synthase inhibitor (Nω-nitro-L-arginine methyl ester) was used to assess SDX's vasodilatory effect over the NO pathway. : SDX application resulted in concentration-dependent vasorelaxation in both endothelium-intact and endothelium-denuded groups at certain doses. However, the inhibitory effect of SDX was more pronounced in endothelium-intact rings at higher doses compared to endothelium-denuded rings ( < 0.05). Similar inhibition of contraction curves was achieved for both endothelium-intact and endothelium-denuded rings after L-NAME pre-incubation, suggesting a necessity for NO-related endothelial pathways. : SDX exerts a concentration-dependent inhibition on arterial contraction, emphasizing the critical role of an intact endothelium and NO-mediated pathways in this process. This underscores SDX's potential in treating endothelial dysfunction-related pathologies.
PubMed: 38673605
DOI: 10.3390/jcm13082332 -
Biomolecules Apr 2024TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine...
TRPC5 is a non-selective cation channel that is expressed in cardiomyocytes, but there is a lack of knowledge of its (patho)physiological role in vivo. Here, we examine the role of TRPC5 on cardiac function under basal conditions and during cardiac hypertrophy. Cardiovascular parameters were assessed in wild-type (WT) and global TRPC5 knockout (KO) mice. Despite no difference in blood pressure or activity, heart rate was significantly reduced in TRPC5 KO mice. Echocardiography imaging revealed an increase in stroke volume, but cardiac contractility was unaffected. The reduced heart rate persisted in isolated TRPC5 KO hearts, suggesting changes in basal cardiac pacing. Heart rate was further investigated by evaluating the reflex change following drug-induced pressure changes. The reflex bradycardic response following phenylephrine was greater in TRPC5 KO mice but the tachycardic response to SNP was unchanged, indicating an enhancement in the parasympathetic control of the heart rate. Moreover, the reduction in heart rate to carbachol was greater in isolated TRPC5 KO hearts. To evaluate the role of TRPC5 in cardiac pathology, mice were subjected to abdominal aortic banding (AAB). An exaggerated cardiac hypertrophy response to AAB was observed in TRPC5 KO mice, with an increased expression of hypertrophy markers, fibrosis, reactive oxygen species, and angiogenesis. This study provides novel evidence for a direct effect of TRPC5 on cardiac function. We propose that (1) TRPC5 is required for maintaining heart rate by regulating basal cardiac pacing and in response to pressure lowering, and (2) TRPC5 protects against pathological cardiac hypertrophy.
Topics: Animals; TRPC Cation Channels; Cardiomegaly; Mice, Knockout; Mice; Heart Rate; Male; Myocytes, Cardiac; Mice, Inbred C57BL; Blood Pressure
PubMed: 38672459
DOI: 10.3390/biom14040442 -
RSC Advances Apr 2024Cucurbiturils (CB) are known to establish stable host-guest complexes with a variety of drug molecules. Herein, the supramolecular complexation between cucurbit[7]uril...
Cucurbiturils (CB) are known to establish stable host-guest complexes with a variety of drug molecules. Herein, the supramolecular complexation between cucurbit[7]uril (CB7) and phenylephrine hydrochloride is reported in aqueous solution. Phenylephrine forms inclusion complex with CB7 with high binding affinity ( = 4.0 × 10 M), which allows for the development of a fluorescence-based sensing assay applying the dye displacement strategy. The structure of the host-guest inclusion complex is investigated by H NMR spectroscopy, in which complexation-induced chemical shifts indicate the immersion of the aromatic ring inside the hydrophobic cavity of CB7. Density functional theory (DFT) calculations support the H NMR results, and reveal that the complex is stabilized through intermolecular interactions between the polar groups on the phenylephrine and the carbonyl rims of CB7, as well as the hydrophobic effect. Moreover, preferential binding of phenylephrine in its protonated over the neutral form results in a complexation-induced p shift.
PubMed: 38655473
DOI: 10.1039/d4ra01910e