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Neuropathic pain, a common symptom of several disorders, exerts a substantial socioeconomic burden worldwide. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel predominantly ex-pressed in nociceptive neurons, plays a pivotal role in nociception, by detecting various endogenous and exogenous stimuli, including heat, pro-inflammatory mediators, and physical stressors. Dysregulation of TRPV1 signaling further contributes to the pathophysiology of neuropathic pain. Therefore, targeting TRPV1 is a promising strategy for developing novel analgesics with improved efficacy and safety profiles. Several pharmacological approaches to modulate TRPV1 activity, including agonists, antagonists, and biological TRPV1 RNA interference (RNAi, small interfering RNA [siRNA]) have been explored. Despite preclinical success, the clinical translation of TRPV1-targeted therapies has encountered challenges, including hyperthermia, hypothermia, pungency, and desensitization. Nevertheless, ongoing research efforts aim to refine TRPV1-targeted interventions through structural modifications, development of selective modulators, and discovery of natural, peptide-based drug candidates. Herein, we provide guidance for researchers and clinicians involved in the development of new interventions specifically targeting TRPV1 by reviewing the existing literature and highlighting current research activities. This study further discusses potential future research endeavors for enhancing the efficacy, safety, and tolerability of TRPV1 candidates, and thereby facilitates the translation of these discoveries into effective clinical interventions to alleviate neuropathic pain disorders.
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Hormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on the transient receptor potential vanilloid 1 (TRPV1). Both endogenous and synthetic GLP-1 and an antagonist of GLP-1, exendin 9-39, reduced heat sensitivity in naïve mice. GLP-1-derived peptides (liraglutide, exendin-4, and exendin 9-39) effectively inhibited capsaicin (CAP)-induced currents and calcium responses in cultured sensory neurons and TRPV1-expressing cell lines. Notably, the exendin 9-39 alleviated CAP-induced acute pain, as well as chronic pain induced by complete Freund's adjuvant (CFA) and spared nerve injury (SNI) in mice, without causing hyperthermia associated with other TRPV1 inhibitors. Electrophysiological analyses revealed that exendin 9-39 binds to the extracellular side of TRPV1, functioning as a noncompetitive inhibitor of CAP. Exendin 9-39 did not affect proton-induced TRPV1 activation, suggesting its selective antagonism. Among exendin 9-39 fragments, exendin 20-29 specifically binds to TRPV1, alleviating pain in both acute and chronic pain models without interfering with GLP-1R function. Our study revealed a novel role for GLP-1 and its derivatives in pain relief, proposing exendin 20-29 as a promising therapeutic candidate.
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Obesity negatively affects hemodynamics and cerebral physiology. We investigated the effect of the utilization of an intermittent pneumatic compression (IPC) device on hemodynamics and cerebral physiology in patients undergoing laparoscopic bariatric surgery under general anesthesia with lung-protective ventilation. Sixty-four patients (body mass index > 30 kg/m2) were randomly assigned to groups that received an IPC device (IPC group, n = 32) and did not (control group, n = 32). The mean arterial pressure (MAP), heart rate (HR), need for vasopressors, cerebral oxygen saturation (rSO2), and cerebral desaturation events were recorded. The incidence of intraoperative hypotension was not significantly different between groups (p = 0.153). Changes in MAP and HR over time were similar between groups (p = 0.196 and p = 0.705, respectively). The incidence of intraoperative cerebral desaturation was not significantly different between groups (p = 0.488). Changes in rSO2 over time were similar between the two groups (p = 0.190) during pneumoperitoneum. Applying IPC to patients with obesity in the steep reverse Trendelenburg position may not improve hemodynamic parameters, vasopressor requirements, or rSO2 values during pneumoperitoneum under lung-protective ventilation. During laparoscopic bariatric surgery, IPC alone has limitations in improving hemodynamics and cerebral physiology.
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Chronic pain is an unpleasant experience associated with actual or potential tissue damage. Inflammatory pain alerts the body to inflammation and promotes healing; however, unresolved inflammation can lead to chronic pain. Conversely, neuropathic pain, due to somatosensory damage, can be a disease in itself. However, inflammation plays a considerable role in the progression of both types of pain. Resolvins, derived from omega-3 fatty acids, actively suppress pro-inflammatory mediators and aid in the resolution of inflammation. Resolvins alleviate various inflammatory and neuropathic pain models by reducing hypersensitivity and regulating inflammatory cytokines and glial activation in the spinal cord and dorsal root ganglia. Thus, resolvins are a promising alternative for pain management with the potential to reduce the side effects associated with conventional medications. Continued research is crucial to unlock the therapeutic potential of resolvins and integrate them into effective clinical pain management strategies. This review aimed to evaluate the literature surrounding the resolvins in inflammatory and neuropathic pain.
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BACKGROUND Remimazolam has the advantage of better hemodynamic stability compared with other anesthetics. We compared the effects of remimazolam and sevoflurane on cerebral oxygenation, intracranial pressure, and intraoperative hemodynamic parameters during mild hypercapnia in patients undergoing laparoscopy in the Trendelenburg position. MATERIAL AND METHODS Sixty-two patients (20-65 years old) scheduled for gynecological laparoscopy were randomly allocated to either the remimazolam (n=31) or sevoflurane (n=31) group. Respiratory and hemodynamic parameters and regional cerebral oxygen saturation (rSO2) were recorded. Intracranial pressure was measured using the optic nerve sheath diameter (ONSD). RESULTS The change over time in rSO2 did not differ between groups (P=0.056). The change in ONSD over time showed a significant intergroup difference (P=0.002). ONSD significantly changed over time (P=0.034) in the sevoflurane group but not in the remimazolam group (P=0.115). The changes in mean arterial pressure and heart rate over time showed significant intergroup differences (P=0.045 and 0.031, respectively). The length of stay and the use of rescue antiemetics and analgesics in the postanesthetic care unit were significantly lower in the remimazolam group than in the sevoflurane group (P=0.023, 0.038, and 0.018, respectively). CONCLUSIONS Remimazolam can provide a favorable hemodynamic profile and attenuate the increase in ONSD during gynecological laparoscopy compared with sevoflurane anesthesia during lung-protective ventilation with mild hypercapnia. Remimazolam can provide faster and better postoperative recovery than sevoflurane anesthesia.
Subject(s)
Anesthesia , Laparoscopy , Humans , Young Adult , Adult , Middle Aged , Aged , Sevoflurane/pharmacology , Intracranial Pressure , Hypercapnia , LungABSTRACT
We compared the effects of pressure-controlled volume-guaranteed ventilation (PCV) and volume-controlled ventilation (VCV) on respiratory mechanics and mechanical power (MP) in elderly patients undergoing laparoscopy. Fifty patients aged 65-80 years scheduled for laparoscopic cholecystectomy were randomly assigned to either the VCV group (n = 25) or the PCV group (n = 25). The ventilator had the same settings in both modes. The change in MP over time was insignificant between the groups (p = 0.911). MP significantly increased during pneumoperitoneum in both groups compared with anesthesia induction (IND). The increase in MP from IND to 30 min after pneumoperitoneum (PP30) was not different between the VCV and PCV groups. The change in driving pressure (DP) over time were significantly different between the groups during surgery, and the increase in DP from IND to PP30 was significantly higher in the VCV group than in the PCV group (both p = 0.001). Changes in MP during PCV and VCV were similar in elderly patients, and MP increased significantly during pneumoperitoneum in both groups. However, MP did not reach clinical significance (≥12 J/min). In contrast, the PCV group had a significantly lower increase in DP after pneumoperitoneum than the VCV group.
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Background: This study aimed to evaluate whether a low- or high-pressure alveolar recruitment maneuver (ARM) might reduce postoperative pain and improve the quality of recovery after laparoscopic bariatric surgery. Methods: 90 patients with a body mass index > 30 kg/m2 scheduled for laparoscopic sleeve gastrectomy were randomly assigned to control (n = 30), low ARM (n = 30), or high ARM groups (n = 30). For the low and high ARM groups, ARM was repeated five times to hold the peak airway pressure at 30 cmH2O and 60 cmH2O for 5 s, respectively, before removal of the trocar. Conventional methods to reduce post-laparoscopic pain, such as intraperitoneal saline irrigation, hemovac drainage, and gentle abdominal compression were performed in all patients, regardless of the assigned group. Results: Shoulder and surgical site pain scores 24 h postoperatively and rescue meperidine requirement were similar between the groups (p = 0.141, 0.101, and 0.82, respectively). The quality of recovery 40 (QoR40) score 24 h postoperatively was similar between the groups (p = 0.755). Postoperative pulmonary complications were similar between the groups (p = 0.124). Conclusion: Application of a low- or high-pressure ARM in addition to conventional methods to remove remnant peritoneal CO2 gas did not reduce postoperative shoulder or surgical site pain or improve the quality of recovery after laparoscopic sleeve gastrectomy.
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The transient receptor potential vanilloid 1 (TRPV1) ion channel plays an important role in the peripheral nociceptive pathway. TRPV1 is a polymodal receptor that can be activated by multiple types of ligands and painful stimuli, such as noxious heat and protons, and contributes to various acute and chronic pain conditions. Therefore, TRPV1 is emerging as a novel therapeutic target for the treatment of various pain conditions. Notably, various peptides isolated from venomous animals potently and selectively control the activation and inhibition of TRPV1 by binding to its outer pore region. This review will focus on the mechanisms by which venom-derived peptides interact with this portion of TRPV1 to control receptor functions and how these mechanisms can drive the development of new types of analgesics.
Subject(s)
Toxins, Biological , Venoms , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Drug Development , Pain/drug therapy , Peptides/metabolism , Peptides/pharmacology , Peptides/therapeutic use , TRPV Cation Channels/metabolism , Venoms/pharmacology , Venoms/therapeutic useABSTRACT
Cerebral hemodynamics may be altered by hypercapnia during a lung-protective ventilation (LPV), CO2 pneumoperitoneum, and Trendelenburg position during general anesthesia. The purpose of this study was to compare the effects of normocapnia and mild hypercapnia on the optic nerve sheath diameter (ONSD), regional cerebral oxygen saturation (rSO2), and intraoperative respiratory mechanics in patients undergoing gynecological laparoscopy under total intravenous anesthesia (TIVA). Sixty patients (aged between 19 and 65 years) scheduled for laparoscopic gynecological surgery in the Trendelenburg position. Patients under propofol/remifentanil total intravenous anesthesia were randomly assigned to either the normocapnia group (target PaCO2 = 35 mmHg, n = 30) or the hypercapnia group (target PaCO2 = 50 mmHg, n = 30). The ONSD, rSO2, and respiratory and hemodynamic parameters were measured at 5 min after anesthetic induction (Tind) in the supine position, and at 10 min and 40 min after pneumoperitoneum (Tpp10 and Tpp40, respectively) in the Trendelenburg position. There was no significant intergroup difference in change over time in the ONSD (p = 0.318). The ONSD increased significantly at Tpp40 when compared to Tind in both normocapnia and hypercapnia groups (p = 0.02 and 0.002, respectively). There was a significant intergroup difference in changes over time in the rSO2 (p < 0.001). The rSO2 decreased significantly in the normocapnia group (p = 0.01), whereas it increased significantly in the hypercapnia group at Tpp40 compared with Tind (p = 0.002). Alveolar dead space was significantly higher in the normocapnia group than in the hypercapnia group at Tpp40 (p = 0.001). In conclusion, mild hypercapnia during the LPV might not aggravate the increase in the ONSD during CO2 pneumoperitoneum in the Trendelenburg position and could improve rSO2 compared to normocapnia in patients undergoing gynecological laparoscopy with TIVA.
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Transient receptor potential (TRP) channels are transmembrane protein complexes that play important roles in the physiology and pathophysiology of both the central nervous system (CNS) and the peripheral nerve system (PNS). TRP channels function as non-selective cation channels that are activated by several chemical, mechanical, and thermal stimuli as well as by pH, osmolarity, and several endogenous or exogenous ligands, second messengers, and signaling molecules. On the pathophysiological side, these channels have been shown to play essential roles in the reproductive system, kidney, pancreas, lung, bone, intestine, as well as in neuropathic pain in both the CNS and PNS. In this context, TRP channels have been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and epilepsy. Herein, we focus on the latest involvement of TRP channels, with a special emphasis on the recently identified functional roles of TRP channels in neurological disorders related to the disruption in calcium ion homeostasis.
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PURPOSE: Controversy remains over whether alveolar recruitment maneuvers (ARMs) can reduce postoperative pulmonary complications. We hypothesized that performing an ARM in addition to lung protective ventilation (LPV) could improve intraoperative arterial oxygenation and postoperative pulmonary complications (PPCs) in elderly patients undergoing laparoscopy in the Trendelenburg position. PATIENTS AND METHODS: Sixty-two patients (aged 65-85) scheduled for laparoscopic low anterior resection were randomized to receive LPV only (LPV group, n = 32) or LPV with an ARM (ARM group, n = 30). LPV was set to a tidal volume of 6 mL/kg with a positive end expiratory pressure (PEEP) of 5 cmH2O. The ARM was performed by serially increasing the PEEP to 10 cmH2O for 3 breaths, 15 cmH2O for 3 breaths, then 20 cmH2O for 10 breaths, both immediately before and after abdominal insufflation. The primary end-point was the frequency of PPCs such as desaturation (SpO2 <90%), atelectasis, and pneumonia. Secondary end-points were changes in intraoperative respiratory and gas exchange parameters and hemodynamic variables. RESULTS: One patient in the LPV group experienced desaturation on the first postoperative day. The frequency of chest X-ray abnormalities such as atelectasis or pleural effusion was comparable between groups (6 (19%) and 5 (17%) patients, respectively, P = 0.676). Changes in other respiratory, gas exchange and hemodynamic parameters over time were not significantly different between the groups. However, vasopressor requirements during surgery were higher in the ARM than the LPV group (9 (30%) and 2 (6%) patients, respectively, P = 0.014). CONCLUSION: This study suggests that performing an ARM during LPV may not improve postoperative respiratory outcomes and intraoperative oxygenation compared to LPV alone in geriatric patients undergoing laparoscopy in the Trendelenburg position. In addition, since the ARM could cause a significant deterioration in hemodynamic parameters, applying ARM to elderly patients should be carefully considered.
Subject(s)
Hypoxia/etiology , Laparoscopy/methods , Positive-Pressure Respiration/adverse effects , Postoperative Complications/etiology , Respiration, Artificial/adverse effects , Aged , Aged, 80 and over , Female , Hemodynamics , Humans , Hypoxia/prevention & control , Laparoscopy/adverse effects , Male , Postoperative Complications/prevention & control , Postoperative Period , Pulmonary Atelectasis/etiology , Surgical Procedures, Operative/adverse effects , Tidal VolumeABSTRACT
INTRODUCTION: This paper presents a novel technique for the synthesis of graphene oxide (GO) with various surface features using high-density atmospheric plasma deposition. Furthermore, to investigate the use of hydrophobic, super-hydrophobic, and hydrophilic graphene in biological applications, we synthesized hydrophobic, super-hydrophobic, and hydrophilic graphene oxides by additional heat treatment and argon plasma treatment, respectively. In contrast to conventional fabrication procedures, reduced graphene oxide (rGO) formed under low pressure and high-temperature environment using a new synthesis method-developed and described in this study-offers a convenient deposition method on any kind surface with controlled wettability. METHODS: High density at atmospheric plasma is used for the synthesis of rGO and GO and its biocompatibility based on various wetting properties was evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and the viability of cells in response to rGO and GO with various surface features was investigated. Structural integrity was characterized by Raman spectroscopy, FESEM and FE-TEM. Wettability was measured via contact angle method and confirmed with XPS analysis. RESULTS: We found that GO coating with a hydrophilic feature is more biocompatible than other surfaces as observed in case of fibroblast cells. We have shown that wettability-controlled by GO deposition-influences biocompatibilities and antibacterial effect of biomaterial surfaces. DISCUSSION: Measuring the contact angle, it is found that contact angle for hydrophobic is increased to 150.590 and reduced to 11.580 by heat and argon plasma treatment, respectively, from 75.880 that was initially in the case of hydrophobic surface. XPS analysis confirmed various oxygen-containing functional groups transforming as deposited hydrophobic surface into superhydrophobic and hydrophilic surface. Thus, we have proposed a new, direct, cost-effective, and highly productive method for the synthesis of rGO and GO-with various surface properties-for biological applications. Similarly, for the dental implant application, the Streptococcus mutans was used as an antibacterial effect and found that S. mutans grows slowly on hydrophilic surface. Thus, antibacterial effect was prominent on GO with hydrophilic surface.
Subject(s)
Atmosphere/chemistry , Graphite/chemical synthesis , Plasma Gases/pharmacology , Animals , Cell Death/drug effects , Cell Line , Graphite/chemistry , Mice , Microbial Viability/drug effects , Oxidation-Reduction , Streptococcus mutans/drug effects , Water , WettabilityABSTRACT
While both baseline regional cerebral oxygen saturation (rSO2) and intraoperative rSO2 decreases have prognostic importance in cardiac surgery, evidence is limited in patients who received interventions to correct rSO2 decreases. The primary aim was to examine the association between rSO2 values (both baseline rSO2 and intraoperative decrease in rSO2) with the composite of morbidity endpoints. We retrospectively analyzed 356 cardiac surgical patients having continuously recorded data of intraoperative rSO2 values. Per institutional guidelines, patients received interventions to restore the rSO2 value to ≥80% of the baseline value. Analyzed rSO2 variables included baseline value, and area under the threshold below an absolute value of 50% (AUT50). Their association with outcome was analyzed with multivariable logistic regression. AUT50 (odds ratio, 1.05; 95% confidence interval; 1.01-1.08; p = 0.015) was shown to be an independent risk factor (along with age, chronic kidney disease, and cardiopulmonary bypass time) of adverse outcomes. In cardiac surgical patients who received interventions to correct decreases in rSO2, increased severity of intraoperative decrease in rSO2 as reflected by AUT below an absolute value of 50% was associated with a composite of adverse outcomes, implicating the importance of cerebral oximetry to monitor the brain as an index organ.
Subject(s)
Antiemetics/therapeutic use , Breast Neoplasms/surgery , Dexamethasone/therapeutic use , Dexmedetomidine/therapeutic use , Mastectomy , Adult , Aged , Drug Therapy, Combination , Female , Hemodynamics , Humans , Incidence , Middle Aged , Postoperative Nausea and Vomiting/drug therapy , Postoperative Nausea and Vomiting/epidemiology , Young AdultABSTRACT
The pectoral nerve block type II (Pecs II block) can provide adequate perioperative analgesia in breast surgery. The surgical pleth index (SPI) is used to monitor the nociception balance using pulse oximetry. We investigated the remifentanil-sparing effect of Pecs II block under SPI guided analgesia during total intravenous anesthesia (TIVA). Thirty-nine patients undergoing breast surgery under remifentanil-propofol anesthesia were randomly assigned to the intervention (Pecs group, n = 20) or control group (n = 19). Remifentanil and propofol concentrations were adjusted to maintain an SPI of 20-50 and a bispectral index of 40-60, respectively. The Pecs group received an ultrasound-guided Pecs II block preoperatively using 30 mL of 0.5% ropivacaine. Total infused remifentanil during the surgery was significantly less in the Pecs group than in the control group (6.8 ± 2.2 µg/kg/h vs. 10.1 ± 3.7 µg/kg/h, p = 0.001). Pain scores on arrival at the postanesthetic care unit (PACU) (3 (2-5) vs. 5 (4-7)) and the rescue analgesic requirement in the PACU (9 vs. 2) was significantly lower in the Pecs group than in the control group. In conclusion, Pecs II block was able to reduce the intraoperative remifentanil consumption by approximately 30% and improve the postoperative pain in PACU in patients undergoing breast surgery under SPI-guided analgesia during TIVA.
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BACKGROUND: Postoperative desaturation in older individuals is rarely addressed in the literature. The objective of this retrospective study was to investigate whether a preoperative spirometric test and arterial blood gas analysis (ABGA) might predict postoperative desaturation after spinal anesthesia in extreme older patients. METHODS: The medical records of 399 patients (age ≥ 80 yrs) who were administered spinal anesthesia for a femur neck fracture surgery were retrospectively reviewed. Early postoperative desaturation was defined as a reduction of oxygen saturation (SpO2) below 90% within 3 days of surgery, despite O2 supply via a nasal prong. Binary logistic regression analysis was used to identify predictors of early postoperative desaturation. RESULTS: The incidence of postoperative desaturation was 12.5%. Major morbidity rate was significantly higher in the desaturation group (n = 50) than that in the non-desaturation group (n = 349) (14% vs. 3.2%, P = 0.001) with more frequent postoperative stays in the intensive care unit (22% vs. 12%, P = 0.004). In a binary logistic regression analysis, preoperative ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2 ratio) (OR, 0.972; 95% CI 0.952-0.993; P = 0.010) and history of cardiovascular disease (OR, 2.127; 95% CI 1.004-4.507; P = 0.049) predicted postoperative desaturation. CONCLUSIONS: Preoperative PaO2/FiO2 ratio, but not preoperative spirometry, was predictive of the postoperative desaturation in older patients after being administered spinal anesthesia for femur fracture surgery. Based on our results, preoperative ABGA may be helpful in predicting early postoperative desaturation in these patients.
Subject(s)
Anesthesia, Spinal/adverse effects , Femoral Neck Fractures/surgery , Hypoxia/etiology , Postoperative Complications/etiology , Aged, 80 and over , Carbon Dioxide/blood , Female , Forced Expiratory Volume/physiology , Frail Elderly , Humans , Hypoxia/blood , Intensive Care Units , Male , Oxygen/blood , Partial Pressure , Patient Admission/statistics & numerical data , Postoperative Complications/blood , Predictive Value of Tests , Preoperative Care/methods , Retrospective Studies , Spirometry , Vital Capacity/physiologyABSTRACT
With the rapid development of diagnostic and therapeutic procedures performed outside the operating room (OR), the need for appropriate sedation care has emerged in importance to ensure the safety and comfort of patients and clinicians. The preparation and administration of sedatives and sedation care outside the OR require careful attention, proper monitoring systems, and clinically useful sedation guidelines. This literature review addresses proper monitoring and selection of sedatives for diagnostic and interventional procedures outside the OR. As the depth of sedation increases, respiratory depression and cardiovascular suppression become serious, necessitating careful surveillance using appropriate monitoring equipment.
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Conscious Sedation/methods , Operating Rooms , Analgesics/pharmacology , Humans , Hypnotics and Sedatives/pharmacology , Monitoring, PhysiologicABSTRACT
BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) is an alternative option to medical treatment for secondary prevention for cryptogenic stroke (CS). Despite technical success of procedure, residual shunt (RS) which is a presumable cause for recurrent stroke is observed in some patients. We evaluated the RS with serial follow-up bubble contrast transesophageal echocardiography (BCTEE) after PFO closure. METHODS: Among consecutive 47 CS patients who underwent PFO closure, a serial follow-up BCTEE at 3 and 9 months after the index procedure was completed in 38 patients (81%, 46 ± 10 years, 19 men). To evaluate the efficacy of PFO closure, the incidence of any and significant RS (≥ moderate) was assessed. RESULTS: All PFO closure procedures were successful. The Amplatzer PFO Occluder (nâ¯=â¯19) or the Gore Septal Occluder (nâ¯=â¯19) were used. Any RS was observed in 13 (34%) and 10 patients (26%) at 3 and 9 months after the procedure. Significant RS was observed in 6 (16%) and 4 (11%) patients at 3- and 9-month follow-up BCTEE. Patients who were treated with the Gore Septal Occluder have a less incidence of any RS in 3 months, and any/significant RS in 3- and 9-month follow-up BCTEE without statistical significance. CONCLUSIONS: RS grade keeps decreasing after PFO closure, but it remains even after 9 months in some patients. Incomplete sealing of PFO should be taken into consideration in management of CS patients even after technically successful PFO closure.
Subject(s)
Cardiac Catheterization/instrumentation , Contrast Media/administration & dosage , Echocardiography, Transesophageal , Foramen Ovale, Patent/therapy , Microbubbles , Secondary Prevention/instrumentation , Septal Occluder Device , Stroke/prevention & control , Adult , Cardiac Catheterization/adverse effects , Female , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/diagnostic imaging , Foramen Ovale, Patent/physiopathology , Humans , Male , Middle Aged , Predictive Value of Tests , Prosthesis Design , Secondary Prevention/methods , Stroke/diagnostic imaging , Stroke/etiology , Stroke/physiopathology , Time Factors , Treatment OutcomeABSTRACT
Dexmedetomidine, an α2-adrenoceptor agonist, is widely used as a sedative and analgesic agent in a number of clinical applications. However, little is known about the mechanism by which it exerts its analgesic effects on the trigeminal system. Two types of voltage-gated sodium channels, Nav1.7 and Nav1.8, as well as α2-adrenoceptors are expressed in primary sensory neurons of the trigeminal ganglion (TG). Using whole-cell patch-clamp recordings, we investigated the effects of dexmedetomidine on voltage-gated sodium channel currents (INa) via α2-adrenoceptors in dissociated, small-sized TG neurons. Dexmedetomidine caused a concentration-dependent inhibition of INa in small-sized TG neurons. INa inhibition by dexmedetomidine was blocked by yohimbine, a competitive α2-adrenoceptor antagonist. Dexmedetomidine-induced inhibition of INa was mediated by G protein-coupled receptors (GPCRs) as this effect was blocked by intracellular perfusion with the G protein inhibitor GDPß-S. Our results suggest that the INa inhibition in small-sized TG neurons, mediated by the activation of Gi/o protein-coupled α2-adrenoceptors, might contribute to the analgesic effects of dexmedetomidine in the trigeminal system. Therefore, these new findings highlight a potential novel target for analgesic drugs in the orofacial region.
Subject(s)
Dexmedetomidine/pharmacology , Receptors, Adrenergic, alpha-2/metabolism , Trigeminal Ganglion/metabolism , Voltage-Gated Sodium Channels/metabolism , Action Potentials/drug effects , Action Potentials/genetics , Animals , Cells, Cultured , Male , Mice , Mice, Inbred C57BL , Trigeminal Ganglion/drug effects , Voltage-Gated Sodium Channels/drug effectsABSTRACT
BACKGROUND: To compare the effects of intraoperative infusions of balanced electrolyte solution (BES)-based hydroxyethyl starch (HES) and saline-based albumin on metabolic acidosis and acid/base changes during major abdominal surgery conducted using Stewart's approach. METHODS: Forty patients, aged 20-65 years, undergoing major abdominal surgery, were randomly assigned to the HES group (n = 20; received 500 ml of BES-based 6% HES 130/0.4) or the albumin group (n = 20; received 500 ml of normal saline-based 5% albumin). Acid-base parameters were measured and calculated using results obtained from arterial blood samples taken after anesthesia induction (T1), 2 hours after surgery commencement (T2), immediately after surgery (T3), and 1 hour after arriving at a postanesthetic care unit (T4). RESULTS: Arterial pH in the HES group was significantly higher than that in the albumin group at T3 (7.40 ± 0.04 vs. 7.38 ± 0.04, P = 0.043), and pH values exhibited significant intergroup difference over time (P = 0.002). Arterial pH was significantly lower at T3 and T4 in the HES group and at T2, T3, and T4 in the albumin group than at T1. Apparent strong ion difference (SIDa) was significantly lower at T2, T3, and T4 than at T1 in both groups. Total plasma weak nonvolatile acid (ATOT) was significantly lower in the HES group than in the albumin group at T2, T3 and T4 and exhibited a significant intergroup difference over time (P < 0.001). CONCLUSIONS: BES-based 6% HES infusion was associated with lower arterial pH values at the end of surgery than saline-based 5% albumin infusion, but neither colloid caused clinically significant metabolic acidosis (defined as an arterial pH < 7.35).