ABSTRACT
BACKGROUND: Recent clinical research suggests that repeated use of opioid pain medications can increase neuropathic pain in people living with human immunodeficiency virus (HIV; PLWH). Therefore, it is significant to elucidate the exact mechanisms of HIV-related chronic pain. HIV infection and chronic morphine induce proinflammatory factors, such as tumor necrosis factor (TNF)α acting through tumor necrosis factor receptor I (TNFRI). HIV coat proteins and/or chronic morphine increase mitochondrial superoxide in the spinal cord dorsal horn (SCDH). Recently, emerging cytoplasmic caspase-11 is defined as a noncanonical inflammasome and can be activated by reactive oxygen species (ROS). Here, we tested our hypothesis that HIV coat glycoprotein gp120 with chronic morphine activates a TNFRI-mtROS-caspase-11 pathway in rats, which increases neuroinflammation and neuropathic pain. METHODS: Neuropathic pain was induced by repeated administration of recombinant gp120 with morphine (gp120/M) in rats. Mechanical allodynia was assessed using von Frey filaments, and thermal latency using hotplate test. Protein expression of spinal TNFRI and cleaved caspase-11 was examined using western blots. The image of spinal mitochondrial superoxide was examined using MitoSox Red (mitochondrial superoxide indicator) image assay. Immunohistochemistry was used to examine the location of TNFRI and caspase-11 in the SCDH. Intrathecal administration of antisense oligodeoxynucleotide (AS-ODN) against TNFRI, caspase-11 siRNA, or a scavenger of mitochondrial superoxide was given for antinociceptive effects. Statistical tests were done using analysis of variance (1- or 2-way), or 2-tailed t test. RESULTS: Intrathecal gp120/M induced mechanical allodynia and thermal hyperalgesia lasting for 3 weeks ( P < .001). Gp120/M increased the expression of spinal TNFRI, mitochondrial superoxide, and cleaved caspase-11. Immunohistochemistry showed that TNFRI and caspase-11 were mainly expressed in the neurons of the SCDH. Intrathecal administration of antisense oligonucleotides against TNFRI, Mito-Tempol (a scavenger of mitochondrial superoxide), or caspase-11 siRNA reduced mechanical allodynia and thermal hyperalgesia in the gp120/M neuropathic pain model. Spinal knockdown of TNFRI reduced MitoSox profile cell number in the SCDH; intrathecal Mito-T decreased spinal caspase-11 expression in gp120/M rats. In the cultured B35 neurons treated with TNFα, pretreatment with Mito-Tempol reduced active caspase-11 in the neurons. CONCLUSIONS: These results suggest that spinal TNFRI-mtROS-caspase 11 signal pathway plays a critical role in the HIV-associated neuropathic pain state, providing a novel approach to treating chronic pain in PLWH with opioids.
Subject(s)
Chronic Pain , HIV Infections , Neuralgia , Rats , Humans , Animals , Reactive Oxygen Species/metabolism , Hyperalgesia/metabolism , Superoxides/metabolism , Morphine/adverse effects , Chronic Pain/metabolism , Rats, Sprague-Dawley , HIV Infections/metabolism , HIV Infections/pathology , Neuralgia/metabolism , Tumor Necrosis Factor-alpha/metabolism , RNA, Small Interfering/adverse effects , RNA, Small Interfering/metabolism , Spinal Cord/metabolismABSTRACT
OBJECTIVES: The aims of the present study were to evaluate and compare the safety and feasibility, including hospitalization, intensive care unit (ICU) stay, frequency of conversion to general anesthesia (GA), pH, PaCO2, and PaO2, of selected patients who underwent minimally invasive mitral valve surgery (MIMVS) via a right minithoracotomy under conscious sedation (CS) to avoid GA. The authors also aimed to evaluate the perioperative management of spontaneous breathing. DESIGN: A retrospective, observational study. SETTING: Single-center. PARTICIPANTS: This study enrolled 101 patients who underwent MIMVS under CS or GA. INTERVENTIONS: The patients who underwent MIMVS were managed under CS or GA according to indication criteria. MEASUREMENTS AND MAIN RESULTS: ICU stay (p = 0.010), postoperative time until first fluid intake (p < 0.0001), and duration of mechanical ventilation (p = 0.004) were shorter in the CS group than in the GA group. No patients converted to GA from CS. PaCO2 during cardiopulmonary bypass (CPB) in the CS group was significantly lower than that in the GA group. However, PaCO2 at the termination of CPB in the CS group was significantly higher than that in the GA group. CONCLUSIONS: In the CS group, advanced-age patients with comorbidities underwent mitral surgery without postoperative complications. The authors' findings suggested that MIMVS under CS could be a potentially less-invasive method, providing a quicker recovery than MIMVS under GA.
Subject(s)
Anesthesia, Conduction , Mitral Valve , Anesthesia, General , Conscious Sedation , Humans , Minimally Invasive Surgical Procedures , Mitral Valve/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
Hypothermic circulatory arrest (HCA) is an essential procedure during aortic surgery to protect organs; however, hypothermia is believed to cause coagulopathy, which is a major fatal complication. This study aimed to clarify the impact of hypothermia on coagulation by eliminating clinical biases in vitro. In the hypothermic storage study, blood samples from five healthy volunteers were stored at 37 â (group N) for 3 h or at 20 â for 2 h, followed by 1 h of rewarming at 37 â (group H). Thromboelastography was performed before and after 3 h of storage. In the mock circulation loop (MCL) study, blood samples were placed in the MCL and (a) maintained at 37 â for 4 h (group N, n = 5), or (b) cooled to 20 â to simulate HCA with a 0.1 L/min flow rate for 3 h and then rewarmed to 37 â (group H, n = 5). The total MCL duration was 4 h, and the flow rate was maintained at 1 L/min, except during HCA. Blood samples collected 15 min after the beginning and end of MCL were subjected to standard laboratory tests and rotational thromboelastometry analyses. Hypothermia had no impact on coagulation in both the hypothermic storage and MCL studies. MCL significantly decreased the platelet counts and clot elasticity in the INTEM and EXTEM assays; however, there was no effect on fibrinogen contribution measured by FIBTEM. Hypothermia does not cause irreversible coagulopathy in vitro; however, MCL decreases coagulation due to the deterioration of platelets.
Subject(s)
Blood Coagulation Disorders , Heart Arrest , Hypothermia , Humans , Hypothermia/etiology , Blood Coagulation Disorders/etiology , Thrombelastography/methods , Blood Coagulation , FibrinogenABSTRACT
OBJECTIVE: This study aimed to compare measurements of right ventricular function using three-dimensional transesophageal echocardiography (3D TEE), and pulmonary artery catheters (PACs) in patients undergoing cardiac surgery. The authors examined the practicality of using the 3D TEE. DESIGN: Prospective observational. SETTING: Cardiac operating room at a single university hospital. PARTICIPANTS: All adult patients undergoing elective cardiac surgery at a single tertiary care university hospital over two years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), stroke volume (SV), and right ventricular ejection fraction (RVEF) were measured with both 3D TEE and PACs. Assessments were performed using correlation coefficients, paired t tests, and Bland-Altman plots. Thirty-one patients participated in this study. Each measurement showed good agreement. RVEDV and RVESV were slightly lower on 3D TEE than on PAC (205.9 mL v 220.2 mL, pâ¯=â¯0.0018; 143.0 mL v 155.5 mL, pâ¯=â¯0.0143, respectively), whereas no significant differences were observed for SV and RVEF (31.0% v 31.1%, pâ¯=â¯0.0569; 61.6 mL v 66.9 mL, pâ¯=â¯0.92, respectively). Linear regression analysis showed high correlation between 3D TEE and PAC for RVEDV (râ¯=â¯0.87) and RVESV (râ¯=â¯0.81), and moderate correlation for SV (râ¯=â¯0.67) and RVEF (râ¯=â¯0.67). In the Bland-Altman plot, most patients were within the 95% limits of the agreement throughout all measurements. CONCLUSION: A high correlation was found between measurements made with a PAC and with 3D TEE in the assessment of right ventricular function. Three-dimensional TEE would be a potential alternative to PAC for assessment of right ventricular function during intraoperative periods.
Subject(s)
Echocardiography, Three-Dimensional , Ventricular Function, Right , Adult , Catheters , Echocardiography, Transesophageal , Humans , Pulmonary Artery/diagnostic imaging , Stroke VolumeABSTRACT
BACKGROUND: Several neuraxial techniques have demonstrated effective post-cesarean section analgesia. According to previous reports, it is likely that patient-controlled epidural analgesia (PCEA) without opioids is inferior to intrathecal morphine (IM) alone for post-cesarean section analgesia. However, little is known whether adding PCEA to IM is effective or not. The aim of this study was to compare post-cesarean section analgesia between IM with PCEA and IM alone. METHODS: Fifty patients undergoing elective cesarean section were enrolled in this prospective randomized study. Patients were randomized to one of two groups: IM group and IM + PCEA group. All patients received spinal anesthesia with 12 mg of 0.5% hyperbaric bupivacaine, 10 µg of fentanyl, and 150 µg of morphine. Patients in IM + PCEA group received epidural catheterization through Th11-12 or Th12-L1 before spinal anesthesia and PCEA (basal 0.167% levobupivacaine infusion rate of 6 mL/h, bolus dose of 3 mL in lockout interval of 30 min) was commenced at the end of surgery. A numerical rating scale (NRS) at rest and on movement at 4,8,12,24,48 h after the intrathecal administration of morphine were recorded. In addition, we recorded the incidence of delayed ambulation and the number of patients who requested rescue analgesics. We examined NRS using Bonferroni's multiple comparison test following repeated measures analysis of variance; p < 0.05 was considered as statistically significant. RESULTS: Twenty-three patients in each group were finally analyzed. Mean NRS at rest was significantly higher in IM group than in IM + PCEA group at 4 (2.7 vs 0.6), 8 (2.2 vs 0.6), and 12 h (2.5 vs 0.7), and NRS during mobilization was significantly higher in IM group than in IM + PCEA group at 4 (4.9 vs 1.5), 8 (4.8 vs 1.9), 12 (4.9 vs 2), and 24 h (5.7 vs 3.5). The number of patients who required rescue analgesics during the first 24 h was significantly higher in IM group compared to IM + PCEA group. No significant difference was observed between the groups in incidence of delayed ambulation. CONCLUSIONS: The combined use of PCEA with IM provided better post-cesarean section analgesia compared to IM alone. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000032475). Registered 6 May 2018 - Retrospectively registered.
Subject(s)
Analgesia, Patient-Controlled/methods , Anesthesia, Spinal/methods , Cesarean Section , Morphine/administration & dosage , Pain, Postoperative/prevention & control , Adult , Female , Humans , Pregnancy , Prospective Studies , Young AdultABSTRACT
PURPOSE: We compared the reversal doses of sugammadex in surgical cases in which intraoperative neuromuscular monitor were used, to cases in which intraoperative neuromuscular monitoring was not used, retrospectively. METHODS: Data were collected by reviewing the electronic medical records of patients who received rocuronium and sugammadex during general anesthesia at Asahikawa Medical University Hospital between May 1, 2017 and April 30, 2018. The primary outcome was the reversal dose of sugammadex per patient actual body weight (mg/kg) between the group in which intraoperative neuromuscular monitoring was used (NM+ group) and the group in which intraoperative neuromuscular monitoring was not used (NM- group). RESULTS: A total of 3496 patients were evaluated, with 2544 patients (73%) included in NM+ group and 952 patients (27%) in NM- group. The reversal doses of sugammadex per actual body weight were significantly higher in NM- group compared to NM+ group. In the NM+ group, 521 patients (20%) received < 2 mg/kg sugammadex, 1377 patients (54%) received 2 ~ 2.5 mg/kg sugammadex, and 646 patients (25%) received > 2.5 mg/kg sugammadex. In contrast, 128 patients (13%) received < 2 mg/kg sugammadex, 362 patients (38%) received 2 ~ 2.5 mg/kg sugammadex and 462 patients (49%) received > 2.5 mg/kg sugammadex in NM- group. CONCLUSION: This single-center retrospective study demonstrated that the use of intraoperative neuromuscular monitor reduced the reversal dose of sugammadex.
Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , gamma-Cyclodextrins , Androstanols , Humans , Retrospective Studies , SugammadexABSTRACT
Chronic pain is increasingly recognized as an important comorbidity of HIV-infected patients, however, the exact molecular mechanisms of HIV-related pain are still elusive. CCAAT/enhancer binding proteins (C/EBPs) are expressed in various tissues, including the CNS. C/EBPß, one of the C/EBPs, is involved in the progression of HIV/AIDS, but the exact role of C/EBPß and its upstream factors are not clear in HIV pain state. Here, we used a neuropathic pain model of perineural HIV envelope glycoprotein gp120 application onto the rat sciatic nerve to test the role of phosphorylated C/EBPß (pC/EBPß) and its upstream pathway in the spinal cord dorsal horn (SCDH). HIV gp120 induced overexpression of pC/EBPß in the ipsilateral SCDH compared with contralateral SCDH. Inhibition of C/EBPß using siRNA against C/EBPß reduced mechanical allodynia. HIV gp120 also increased TNFα, TNFRI, mitochondrial superoxide (mtO2·-), and pCREB in the ipsilateral SCDH. ChIP-qPCR assay showed that pCREB enrichment on the C/EBPß gene promoter regions in rats with gp120 was higher than that in sham rats. Intrathecal TNF soluble receptor I (functionally blocking TNFα bioactivity) or knockdown of TNFRI using antisense oligodeoxynucleotide against TNFRI reduced mechanical allodynia, and decreased mtO2·-, pCREB and pC/EBPß. Intrathecal Mito-tempol (a mitochondria-targeted O2·-scavenger) reduced mechanical allodynia and decreased pCREB and pC/EBPß. Knockdown of CREB with antisense oligodeoxynucleotide against CREB reduced mechanical allodynia and lowered pC/EBPß. These results suggested that the pathway of TNFα/TNFRI-mtO2·--pCREB triggers pC/EBPß in the HIV gp120-induced neuropathic pain state. Furthermore, we confirmed the pathway using both cultured neurons treated with recombinant TNFα in vitro and repeated intrathecal injection of recombinant TNFα in naive rats. This finding provides new insights in the understanding of the HIV neuropathic pain mechanisms and treatment.SIGNIFICANCE STATEMENT Painful HIV-associated sensory neuropathy is a neurological complication of HIV infection. Phosphorylated C/EBPß (pC/EBPß) influences AIDS progression, but it is still not clear about the exact role of pC/EBPß and the detailed upstream factors of pC/EBPß in HIV-related pain. In a neuropathic pain model of perineural HIV gp120 application onto the sciatic nerve, we found that pC/EBPß was triggered by TNFα/TNFRI-mtO2·--pCREB signaling pathway. The pathway was confirmed by using cultured neurons treated with recombinant TNFα in vitro, and by repeated intrathecal injection of recombinant TNFα in naive rats. The present results revealed the functional significance of TNFα/TNFRI-mtO2·--pCREB-pC/EBPß signaling in HIV neuropathic pain, and should help in the development of more specific treatments for neuropathic pain.
Subject(s)
CCAAT-Enhancer-Binding Protein-beta/metabolism , Chronic Pain/metabolism , HIV Envelope Protein gp120/pharmacology , Neuralgia/metabolism , Animals , Chronic Pain/virology , Cyclic AMP Response Element-Binding Protein/metabolism , HIV Infections/complications , Male , Neuralgia/virology , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/physiology , Spinal Cord Dorsal Horn/drug effects , Spinal Cord Dorsal Horn/metabolism , Superoxides/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
OBJECTIVE: To evaluate the morphologic changes of the mitral annulus using 3-dimensional transesophageal echocardiography during heart displacement to expose the anastomosis site in off-pump coronary artery bypass surgery (OPCAB). DESIGN: Prospective case series. SETTING: Single center, university hospital. PARTICIPANTS: The study comprised 34 consecutive patients who underwent OPCAB of the left circumflex artery (LCX) and the right coronary artery (RCA). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mitral annulus parameters were measured using the Mitral Valve Quantification program after sternotomy (physiologic position) and during displacement of the heart to expose the LCX (LCX position) and the RCA (RCA position). The height of the mitral annulus was significantly lower in the LCX (5.76 ± 0.90 mm) and RCA (5.92 ± 0.97 mm) positions than in the physiologic position (6.96 ± 0.99 mm; both p < 0.0001). The percent change in the height of the mitral annulus was significantly greater in the mitral regurgitation group than in the mitral regurgitation nondeterioration group when in the LCX (-16.3% ± 6.0% v -11.9% ± 3.3%, p = 0.0203) and RCA (-16.9% ± 6.3% v -12.1% ± 3.8%, p = 0.0207) positions. The anteroposterior and intercommissural diameters, annulus perimeter, and surface area of the mitral annulus did not differ significantly among all heart positions. CONCLUSIONS: The mitral annulus flattened and lost its saddle shape without expanding while in the LCX and RCA positions. The greater percent change in the height of the mitral annulus may aggravate mitral regurgitation.
Subject(s)
Coronary Artery Bypass, Off-Pump/methods , Echocardiography, Three-Dimensional/methods , Echocardiography, Transesophageal/methods , Mitral Valve/diagnostic imaging , Monitoring, Intraoperative/methods , Aged , Coronary Artery Bypass, Off-Pump/adverse effects , Female , Heart/diagnostic imaging , Humans , Male , Prospective StudiesABSTRACT
End-stage renal disease (ESRD) is associated with significant alterations in cardiovascular function; homeostasis of body fluid, electrolytes, and acid-base equilibrium; bone metabolism, erythropoiesis; and blood coagulation. The prevalence of ESRD is increasing rapidly worldwide, as is the number of patients requiring surgery under general anesthesia. Patients with ESRD have significantly higher risks of perioperative morbidity and mortality due to multiple comorbidities. The perioperative management of patients with ESRD under general anesthesia therefore requires special considerations and a careful multidisciplinary approach. In this review, the authors summarize the available literature to address common issues related to patients with ESRD and discuss the best perioperative approach for this patient subgroup.
Subject(s)
Cardiovascular Diseases/surgery , Disease Management , Kidney Failure, Chronic/surgery , Perioperative Care/methods , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Comorbidity , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/epidemiology , Renal Dialysis/adverse effects , Renal Dialysis/trendsABSTRACT
We report a rare case of papillary muscle rupture due to myocardial infarction during left ventricular assist device support. A 69-year-old woman with cardiogenic shock due to acute myocardial infarction requiring venoarterial extracorporeal membrane oxygenation support was transferred for further surgical intervention. Six days after the event, extracorporeal membrane oxygenation was decannulated, and an extracorporeal left ventricular assist device was implanted. On postoperative day 11, she suffered from sudden onset hypoxia due to pulmonary edema. Transesophageal echocardiography showed new onset severe mitral regurgitation. No further surgical intervention was performed according to the family's wishes, and she passed away on the 22nd postoperative day. Autopsy findings revealed papillary muscle rupture. Although the left ventricle is unloaded by the left ventricular assist device, papillary muscle rupture should be recognized as a possible complication after myocardial infarction.
Subject(s)
Extracorporeal Membrane Oxygenation/methods , Heart Rupture, Post-Infarction/diagnosis , Heart-Assist Devices/adverse effects , Aged , Echocardiography, Transesophageal , Female , Heart Rupture, Post-Infarction/surgery , Humans , Papillary MusclesABSTRACT
BACKGROUND: Mitochondria play an important role in many cellular and physiologic functions. Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis. The most common complaint of human immunodeficiency virus (HIV)-sensory neuropathy is pain on the soles in patients with HIV, but the exact molecular mechanisms of HIV neuropathic pain are not clear. In the present study, we investigated the role of mitochondrial dynamin-related protein 1 (Drp1, a GTPase that mediates mitochondrial fission) in the perineural HIV coat glycoprotein gp120-induced neuropathic pain state. METHODS: Neuropathic pain was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. Mechanical threshold was tested using von Frey filaments. The mechanical threshold response was assessed over time using the area under curves. Intrathecal administration of antisense oligodeoxynucleotide (ODN) against Drp1, mitochondrial division inhibitor-1 (mdivi-1), or phenyl-N-tert-butylnitrone (a reactive oxygen species scavenger) was given. The expression of spinal Drp1 was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. RESULTS: Intrathecal administration of either antisense ODN against Drp1 or mdivi-1 decreased mechanical allodynia (a sensation of pain evoked by nonpainful stimuli) in the gp120 model. Intrathecal ODN or mdivi-1 did not change basic mechanical threshold in sham surgery rats. Intrathecal Drp1 antisense ODN decreased the spinal expression of increased Drp1 protein induced by peripheral gp120 application. Intrathecal phenyl-N-tert-butylnitrone reduced mechanical allodynia. Furthermore, both intrathecal Drp1 antisense ODN and mdivi-1 reversed the upregulation of mitochondrial superoxide in the spinal dorsal horn in the gp120 neuropathic pain state. CONCLUSIONS: These data suggest that mitochondrial division plays a substantial role in the HIV gp120-related neuropathic pain state through mitochondrial reactive oxygen species and provides evidence for a novel approach to treating chronic pain in patients with HIV.
Subject(s)
Analgesics/pharmacology , Cyclic N-Oxides/pharmacology , Dynamins/metabolism , Free Radical Scavengers/pharmacology , HIV Envelope Protein gp120 , Hyperalgesia/prevention & control , Mitochondria/drug effects , Oligonucleotides, Antisense/metabolism , Posterior Horn Cells/drug effects , Quinazolinones/pharmacology , Sciatica/prevention & control , Superoxides/metabolism , Analgesics/administration & dosage , Animals , Cyclic N-Oxides/administration & dosage , Disease Models, Animal , Dynamins/genetics , Free Radical Scavengers/administration & dosage , HIV Infections/complications , HIV Infections/virology , Hyperalgesia/genetics , Hyperalgesia/metabolism , Hyperalgesia/physiopathology , Hyperalgesia/virology , Injections, Spinal , Male , Mitochondria/metabolism , Mitochondrial Dynamics/drug effects , Oligonucleotides, Antisense/administration & dosage , Oligonucleotides, Antisense/genetics , Pain Threshold/drug effects , Posterior Horn Cells/metabolism , Quinazolinones/administration & dosage , Rats, Sprague-Dawley , Recombinant Proteins , Sciatica/genetics , Sciatica/metabolism , Sciatica/physiopathology , Sciatica/virology , Time FactorsABSTRACT
BACKGROUND: The goal of this study was to evaluate in patients with peripheral arterial disease (PAD) whether ultrasound-guided radial artery catheterization decreased procedural time and number of attempts compared with the traditional palpation technique. METHODS: Ultrasonography was evaluated for arte- rial catheterization after the traditional palpation tech- nique was unsuccessful in 480 seconds in 10 patients with PAD. The vascular access was performed by a single anesthesiologist. The successful catheterization time and the number of attempts were recorded. We also measured the diameter of the radial artery, the skin-to-artery distance, and the distance between the linear probe and puncture site. RESULTS: The mean overall time per patient for catheter insertion was 220.0?112.6 sec in the ultra- sound group vs. 480 sec in the palpation group (P= 0.0029). The mean number of attempts was 1.30?0.48 in the ultrasound group vs. 4.50?0.53 in the palpation group (P = 0.0024). All catheterizations were success- ful, and no failure was encountered in the ultrasound group. CONCLUSIONS: Ultrasound-guided radial artery cath- eterization took less time to establish the arterial line, and it reduced the number of attempts when com- pared with the palpation technique.
Subject(s)
Radial Artery/diagnostic imaging , Adult , Aged , Catheterization, Peripheral , Female , Humans , Male , Middle Aged , Palpation , Punctures , UltrasonographyABSTRACT
BACKGROUND: Human immunodeficiency virus (HIV)-related painful sensory neuropathies primarily consist of the HIV infection-related distal sensory polyneuropathy and antiretroviral toxic neuropathies. Pharmacotherapy provides only partial relief of pain in patients with HIV/acquired immune deficiency syndrome because little is known about the exact neuropathological mechanisms for HIV-associated neuropathic pain (NP). Hypofunction of γ-aminobutyric acid (GABA) GABAergic inhibitory mechanisms has been reported after peripheral nerve injury. In this study, we tested the hypothesis that HIV gp120 combined with antiretroviral therapy reduces spinal GABAergic inhibitory tone and that restoration of GABAergic inhibitory tone will reduce HIV-related NP in a rat model. METHODS: The application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve plus systemic ddC (one antiretroviral drug) induced mechanical allodynia. The hind paws of rats were inoculated with replication-defective herpes simplex virus (HSV) vectors genetically encoding gad1 gene to express glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes the decarboxylation of glutamate to GABA. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The expression of GAD67 in both the lumbar spinal cord and the L4-5 dorsal root ganglia was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging. The immunoreactivity of spinal GABA, pCREB, and pC/EBPß was tested using immunohistochemistry. RESULTS: In the gp120 with ddC-induced neuropathic pain model, GAD67 expression mediated by the HSV vector caused an elevation of mechanical threshold that was apparent on day 3 after vector inoculation. The antiallodynic effect of the single HSV vector inoculation expressing GAD67 lasted >28 days. The area under the time-effect curves in the HSV vector expressing GAD67 was increased compared with that in the control vectors (P = 0.0005). Intrathecal GABA-A/B agonists elevated mechanical threshold in the pain model. The HSV vectors expressing GAD67 reversed the lowered GABA immunoreactivity in the spinal dorsal horn in the neuropathic rats. HSV vectors expressing GAD67 in the neuropathic rats reversed the increased signals of mitochondrial superoxide in the spinal dorsal horn. The vectors expressing GAD67 reversed the upregulated immunoreactivity expression of pCREB and pC/EBPß in the spinal dorsal horn in rats exhibiting NP. CONCLUSIONS: Based on our results, we suggest that GAD67 mediated by HSV vectors acting through the suppression of mitochondrial reactive oxygen species and transcriptional factors in the spinal cord decreases pain in the HIV-related neuropathic pain model, providing preclinical evidence for gene therapy applications in patients with HIV-related pain states.
Subject(s)
Gene Transfer Techniques , Genetic Therapy/methods , Genetic Vectors , Glutamate Decarboxylase/genetics , HIV Envelope Protein gp120/metabolism , HIV Infections/complications , Sciatic Nerve/enzymology , Sciatica/therapy , Simplexvirus/genetics , Zalcitabine , Animals , CCAAT-Enhancer-Binding Protein-beta/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Decarboxylation , Disease Models, Animal , Glutamate Decarboxylase/biosynthesis , Glutamic Acid/metabolism , HIV Envelope Protein gp120/genetics , HIV Infections/genetics , HIV Infections/metabolism , HIV Infections/virology , Humans , Male , Mitochondria/metabolism , Pain Threshold , Phosphorylation , Rats, Sprague-Dawley , Sciatic Nerve/physiopathology , Sciatic Nerve/virology , Sciatica/enzymology , Sciatica/genetics , Sciatica/physiopathology , Sciatica/virology , Simplexvirus/enzymology , Spinal Cord Dorsal Horn/metabolism , Superoxides/metabolism , Time Factors , gamma-Aminobutyric Acid/metabolismSubject(s)
Cardiac Surgical Procedures , Echocardiography, Transesophageal , Echocardiography , Humans , InternetSubject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/diagnostic imaging , Echocardiography, Transesophageal/adverse effects , Endoscopy, Gastrointestinal/methods , Stomach Rupture/etiology , Suture Techniques , Transcatheter Aortic Valve Replacement , Aged, 80 and over , Aortic Valve/surgery , Aortic Valve Stenosis/diagnosis , Humans , Iatrogenic Disease , Male , Stomach Rupture/diagnosis , Stomach Rupture/surgeryABSTRACT
We report three cases with systolic anterior motion (SAM) after mitral valve plasty. Preoperative mitral valve morphology is a risk factor for SAM. The morphological characteristics of SAM have been revealed in several studies. We found a small distance between coaptation and the interventricular septum in all cases, and cases 2, and 3 had a low AL/PL ratio, whereas case 3 had a large PML, which was revealed by transesophageal echocardiography. With the use of 3D transesophageal echocardiography, when mitral valve prolapse was investigated, in all three cases, it was easy to specify lesions. The issue for the future is 3D analysis when SAM is occurring.
Subject(s)
Adrenergic beta-Antagonists/blood , Anti-Arrhythmia Agents/blood , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/drug therapy , Mitral Valve/drug effects , Mitral Valve/diagnostic imaging , Morpholines/blood , Urea/analogs & derivatives , Adrenergic beta-Antagonists/therapeutic use , Aged , Anti-Arrhythmia Agents/therapeutic use , Echocardiography, Three-Dimensional , Echocardiography, Transesophageal , Female , Humans , Male , Middle Aged , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/surgery , Morpholines/therapeutic use , Preoperative Care , Prognosis , Urea/blood , Urea/therapeutic useABSTRACT
We report a case of 30-second cardiac arrest that occurred during carotid body tumor resection due to the carotid sinus reflex. The patient was a 20-year-old man diagnosed with a carotid body tumor and scheduled for tumor resection. General anesthesia was induced and maintained with target controlled infusion of propofol. Analgesia was achieved with continuous administration of remifentanil. When the surgery was initiated, 1% lidocaine 3 ml was locally injected into the carotid bifurcation. When surgery was initiated in the neck region, the patient developed sudden cardiac arrest. Chest compression was immediately initiated, and atropine 0.5 mg was administered; subsequently circulation was restored. Surgery was resumed after placing a temporary pacemaker through the left subclavian vein. The surgery was successfully performed without any other bradycardia complications, and the patient recovered from general anesthesia without sequelae. Thus, the findings indicate the importance of considering the pacemaker placement before carotid body tumor resection.
Subject(s)
Anesthesia, General , Carotid Body Tumor/surgery , Heart Arrest/therapy , Intraoperative Care , Intraoperative Complications/therapy , Adult , Atropine/administration & dosage , Carotid Sinus/physiopathology , Chest Wall Oscillation , Heart Arrest/etiology , Heart Arrest/prevention & control , Humans , Intraoperative Complications/etiology , Intraoperative Complications/prevention & control , Male , Pacemaker, Artificial , Propofol , Reflex/physiology , Young AdultABSTRACT
BACKGROUND: Nerve injury in epidural labor analgesia can occur with various potential causes. We report a rare case of left common peroneal nerve palsy after delivery caused by a prolonged period of sitting cross-legged during epidural labor. CASE REPORT: Epidural labor analgesia in a 28-year-old primipara started at 39 weeks of gestation. She sat cross-legged to prompt delivery for approximately 4 h with a break of a few minutes every hour. She had numbness in her left lower limb and difficulty in dorsiflexion of the ankle joint that did not improve until 3 h after delivery. We made a diagnosis of left common peroneal nerve palsy. Most of the symptoms had improved at 2 months postpartum. CONCLUSION: Epidural labor analgesia prevented recognition of prolonged peroneal head compression caused by sitting cross-legged. When this position is used to facilitate delivery, it should be released frequently owing to the possibility of a neurologic deficit.