Is Prevention of Postoperative Vomiting Surgery Dependent? A Retrospective Cohort Study of Total Knee Arthroplasty.

The study of postoperative nausea and vomiting (PONV) has been ongoing since the early days of general anesthesia. The search for risk factors of PONV and the development of new agents to treat PONV are the two main strategies to combat the adverse side effects of general anesthesia. Female sex, non-smoking status, a history of PONV/motion sickness, and postoperative opioid use are the four independent risk factors for PONV derived after a series of prospective studies, evidence-based systematic reviews, and meta-analyses. The two frequently asked questions that arise ask whether risk factors apply to different clinical settings and whether prevention measures of PONV can be surgery dependent. We conducted a comprehensive review of 665 patients who underwent primary total knee arthroplasty (TKA) between January and December 2019. As nausea is subjective and its measurement is not standardized, postoperative vomiting (POV) was used as a study endpoint. The exclusion criteria were desflurane anesthesia, spinal anesthesia, anesthesia without bispectral index monitoring, and day surgery. Three well-recognized risk factors, consisting of body weight, sevoflurane consumption, and postoperative opioid consumption, were not considered as independent risk factors of POV, while female sex, preoperative adductor canal block (ACB), and dexamethasone were identified as being so in this study. The risk of POV in the female sex was 2.49 times that in the male sex; however, when dexamethasone was used, this risk was reduced by >40% compared with no antiemetic use, and by >50% when patients received preoperative ACB compared with those without the block. The clinical characteristics of our TKA patients-female dominance, old age, and their fairly constant body weights that were distinct from those of other surgical patients-suggested that age may play a crucial role in determining the relative contributions of the different risk factors of POV. We concluded that risk factors of POV are dependent on clinical settings. Based on these results, it is reasonable to speculate that a surgery-dependent plan for the prevention of POV is feasible for patients in similar clinical settings.

Postoperative Stroke after Spinal Anesthesia and Responses of Carotid or Cerebral Blood Flow and Baroreflex Functionality to Spinal Bupivacaine in Rats.

Spinal anesthesia is generally accepted as an effective and safe practice. Three rare incidents of postoperative cerebral infarction after surgery under spinal anesthesia prompted us to assess whether spinal bupivacaine may compromise carotid or cerebral blood flow. Postoperative examination after the stroke incident revealed that all three patients shared a common pathology of stenosis or atheromatosis in the carotid or middle cerebral artery. In a companion study using 69 Sprague-Dawley rats, subarachnoid application of bupivacaine elicited an initial (Phase I) reduction in the mean arterial pressure, carotid blood flow (CBF) and baroreflex-mediated sympathetic vasomotor tone, all of which subsequently returned to baseline (Phase II). Whereas heart rate (HR) exhibited sustained reduction, cardiac vagal baroreflex, baroreflex efficiency index (BEI) and tissue perfusion and oxygen in the cerebral cortex remained unaltered. However, in one-third of the rats studied, Phase II gave way to Phase III characterized by secondary hypotension and depressed baroreflex-mediated sympathetic vasomotor tone, along with declined HR, sustained cardiac vagal baroreflex, decreased BEI, reduced CBF and waning tissue perfusion or oxygen in the cerebral cortex. We concluded that carotid and cerebral blood flow can indeed be compromised after spinal anesthesia, and an impaired baroreflex-mediated sympathetic vasomotor tone, which leads to hypotension, plays a contributory role.

Chronic Obstructive Pulmonary Disease as a Phenotype of Bronchiectasis for Long-Term Clinical Presentation and Treatment.

Background and Objectives: Bronchiectasis and chronic obstructive pulmonary disease (COPD) often coexist, although the causality is not currently clear. Currently, the clinical influence of COPD on patients with major bronchiectasis over time has not yet been investigated. Material and Methods: This retrospective study recruited consecutive patients with bronchiectasis from outpatient clinic between January 2006 and December 2007. Under the setting of quantification with HRCT, patients who should undergo multiple pulmonary function and exercise tests with regularclinic follow-up were included. The final analysis consisted of 66 eligible patients who were evaluated for clinical status, treatment, and sputum culture from up to 10-year electronic medical records. Results: Of these 66 patients, 45 (68%) had bronchiectasis without COPD and 21 (32%) had COPD. Patients with COPD group had a higher bronchiectasis extent score (32.21 ± 13.09 points vs. 21.89 ± 10.08 points, p = 0.001). Sputum production was reported more frequently by patients with COPD; however, no significant difference was observed after 3 years of follow-up (82.4% vs. 81.6%, p = 0.945). Bronchiectasis extent score correlated with positive sputum culture with Pseudomonas without a synergistic effect from COPD (odds ratio: 1.06, confidence interval: 1.00-1.12, p = 0.031). Regardless of COPD, after 10 years, the proportion of patients using inhaled corticosteroids and/or long-acting ß2-agonist between the two groups was not significantly different. Conclusion: COPD aggravated bronchiectasis extension, which was correlated with chronic Pseudomonas aeruginosa colonisation. Moreover, COPD would affect the medium-term (in 3-5 years) bronchiectasis treatment. Therefore, the COPD phenotype of bronchiectasis could be a clinical predictor of the course of treatment.

Is There an Optimal Timing of Adductor Canal Block for Total Knee Arthroplasty?-A Retrospective Cohort Study.

Adductor canal block (ACB) has gained popularity for postoperative pain control after total knee arthroplasty (TKA). However, its role in TKA has been questioned recently. Our study aimed to clarify the role of ACB in reducing postoperative pain after TKA and to elucidate an optimal timing to perform ACB for better outcomes. We conducted a comprehensive review of the perioperative records of 652 patients undergoing primary TKA from January 2019 to December 2019. Patients were divided into three groups: Group A received general anesthesia without ACB, Group B received ACB before inducing general anesthesia, and Group C received ACB at the post-anesthesia recovery unit (PACU). Patients in Groups B and C had lower pain visual analogue scale (VAS) scores than patients in Group A at the PACU. Opioid consumption was similar among the three groups; however, a slightly higher dose was required by Group A patients. Higher VAS scores were recorded in the ward in Group A than in Groups B and C with the leg at rest. In addition, higher VAS scores were recorded in Group A than in Groups B and C with the leg in continuous passive motion (CPM) training. More patients in Group A (34.9%) quit their first CPM training after a few cycles than those in Groups B (27.0%) and C (20.1%). Group A patients required a higher per kg dose of opioids in the ward than Groups B and C patients. Additionally, the hourly consumption of sevoflurane was similar among the three groups of patients, while Group A and C patients required a higher hourly per kg dose of intraoperative opioids than Group B patients. More patients in Group A (67.6%) and C (61.7%) developed intraoperative hypertension than patients in Group B (52.7%). There was no significant difference in PON (postoperative nausea), POV (postoperative vomiting), postoperative dizziness, or patient satisfaction among the three groups of patients. Group A patients had a longer length of hospital stay compared to Group B and C patients. In conclusion, preoperative ACB could be a better choice for patients undergoing TKA as it decreases intraoperative opioid consumption and facilitates a stable hemodynamic state during surgery.

Sevoflurane versus desflurane for early postoperative vomiting after general anesthesia in hospitalized adults: A systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: This systematic review and meta-analysis aimed at assessing the effects of two commonly used anesthetics in general anesthesia (GA), sevoflurane and desflurane, on early postoperative vomiting (POV) in hospitalized adults. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Early postoperative vomiting after GA. PATIENTS: A total of 266 adult patients receiving inpatient surgeries under GA maintained with sevoflurane or desflurane. INTERVENTIONS: We searched PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect, and Embase for eligible RCTs comparing postoperative outcomes following sevoflurane- or desflurane-maintained anesthesia. MEASUREMENTS: The primary outcome was early POV. Secondary outcomes included late POV, early and late postoperative nausea (PON), time to extubation, and emergence time. MAIN RESULTS: Eight trials were included. There was no significant difference in the risk of early POV (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.64-1.64, p = 0.91). No significant difference in early PON was observed (RR 1.09; 95% CI, 0.77-1.56; p = 0.62). Nevertheless, the incidence of late POV and late PON were significantly lower in the sevoflurane group than that in the desflurane group (RR 0.47, 95% CI 0.23-0.94, p = 0.03; RR 0.45, 95% CI 0.24-0.84, p = 0.01, respectively). The extubation time was longer in the sevoflurane group than in the desflurane group (standardized mean difference [SMD] 0.56, 95% CI 0.14-0.97, p = 0.009). The emergence time of patients in the sevoflurane group was longer than that in those receiving desflurane (SMD 0.76, 95% CI 0.1-1.42, p = 0.02). CONCLUSIONS: Desflurane had the same effects on early POV and early PON as sevoflurane. However, the association between late POV and late PON with desflurane was stronger than that with sevoflurane if the effects of opioids were not considered. The desflurane group had shorter time to extubation and emergence time than the sevoflurane group. PROSPERO registration number: CRD42020218988.

Risk Factors of Postoperative Vomiting in the Eye of "Real-World Evidence"-Modifiable and Clinical Setting-Dependent Risk Factors in Surgical Trauma Patients.

Numerous studies on postoperative nausea and vomiting (PONV) have been carried out since the early days of contemporary surgery. The incidence of PONV has been greatly reduced in recent years and new drugs for PONV keep evolving in the market; however, a substantial number of patients are still under the threat of PONV. Female gender, non-smokers, a history of PONV/motion sickness, and postoperative opioid use are four well-recognized risk factors of PONV. Many potential risk factors reported in previous studies were not consistently presented as predictors for PONV. Two questions then arise; are risk factors clinical setting dependent and are risk factors modifiable? We attempted to answer the questions through a comprehensive review of perioperative records of surgical patients from the Trauma Department of our hospital. As nausea is subjective and no standard is applicable for its measurement, postoperative vomiting (POV) was used as an endpoint in this study. To the best of our knowledge, this is the first study to address the POV issue in surgical trauma patients. A total of 855 patients were enrolled in this study after excluding age below 20 years old, total intravenous anesthesia, desflurane anesthesia, or records with missing data. Our results showed that female gender (OR 4.89) is the strongest predicting factor, followed by a less potent predicting factor-more intraoperative opioid consumption (OR 1.07)-which favor more POV. More intraoperative crystalloid supply (OR 0.71) and a higher body weight (OR 0.9) favor less POV. Other potential risk factors did not reach statistical significance in this study as independent risk factors. Our results also showed that when the intraoperative crystalloid infusion rate is greater than 4 mL/kg/h (OR 0.20), it favors a lower rate of POV; when intraoperative opioid consumption is greater than 12 mg morphine equivalents, MME (OR 1.87), it favors a higher rate of POV. We concluded that dominance of any independent risk factor over other risk factors depends on how individual factors interact with the clinical setting. Some risk factors could be modified, and a cut-off value could be derived to facilitate a better plan for POV prevention.

Postoperative Vomiting Following Laparoscopic Cholecystectomy Is Associated with Intraoperative Fluid Administration: A Retrospective Cohort Study.

Potential risk factors for postoperative vomiting (POV) are important for daily anesthesia practice. To identify the risk factors associated with POV we retrospectively reviewed 553 adult patients who underwent scheduled simple laparoscopic cholecystectomy under sevoflurane-based general anesthesia between January and December 2018. Patients who experienced POV were predominantly women, had lower body weight, and higher ASA (American Society of Anesthesiologists) physical status. The POV group showed female sex predominance, lower body weight, and higher ASA physical status, with a significant difference when compared with the non-POV group. In univariate analysis, female sex and Apfel scores of 2, 3, and 4 were associated with a higher POV incidence. Age > 70 years, higher body weight, and ASA physical status III were associated with a lower POV incidence. In multivariate logistic regression, sex, age, Apfel score, and intraoperative crystalloid infusion rate were POV predictive factors. Receiver operating characteristic analysis showed a negative association between the intraoperative crystalloid infusion rate and POV occurrence with an area under the curve of 0.73 (p = 0.001). The cutoff intraoperative crystalloid infusion rate was 2 mL/kg/h with 82% sensitivity and 49% specificity (≥2 mL/kg/h was associated with a lower POV incidence vs. <2 mL/kg/h (OR, 95% CI; 0.52 [0.33-0.83])). To decrease POV in these patients, identifying high-risk factors and an intraoperative crystalloid administration of ≥2 mL/kg/h should be considered in patients undergoing LC under sevoflurane-based general anesthesia.

Earlier Is Better? Timing of Adductor Canal Block for Arthroscopic Knee Surgery under General Anesthesia: A Retrospective Cohort Study.

The adductor canal block (ACB) is effective for treating postoperative pain during arthroscopic knee surgery, but its impact on anesthesia course and the optimal administration timing are unknown. This retrospective study addressed these questions. The aim of this study was to compare the effects of preoperative ACB and postoperative ACB on anesthesia course and postoperative recovery. We allocated 215 adult patients who underwent arthroscopic knee surgery under sevoflurane anesthesia between January 2019 and December 2019 to three groups. Group A received general anesthesia without ACB, Group B received ACB before general anesthesia induction, and Group C received ACB in the post-anesthesia recovery unit (PACU). Group B consumed significantly less sevoflurane (0.19 mL/kg/h) and milligram morphine equivalents (0.08 MME) intraoperatively than Groups A (0.22 mL/kg/h; 0.10 MME, respectively) and C (0.22 mL/kg/h; 0.09 MME, respectively). Groups B and C had lower visual analogue scale (VAS) scores upon PACU discharge than Group A. Dynamic, but not at-rest VAS scores, were significantly higher in Group A. Opioid consumption was similar in the ward, but Group A requested more intravenous parecoxib for pain relief. Length of hospital stay was similar. Thus, preoperative ACB reduced the amount of volatile anesthetic required and maintained stable hemodynamics intraoperatively. Preoperative or postoperative ACB improved postoperative pain control. Consequently, preoperative ACB is optimal for intraoperative stress suppression and postoperative pain control.

The effect of cricoid pressure on tracheal intubation in adult patients: a systematic review and meta-analysis.

PURPOSE: This meta-analysis aimed to assess the impact of cricoid pressure (CP) application on intubation outcomes. SOURCE: Electronic databases (i.e., MEDLINE, PubMed, Embase, and Cochrane review) were searched from inception to 2 June 2020 for randomized-controlled trials that assessed the intubation outcomes in adult patients using laryngoscopic approaches with and without the application of CP (i.e., CP vs non-CP group). The primary outcome was the successful first-attempt intubation rate (SFAIR), and the secondary outcomes were intubation time, incidences of poor laryngoscopic views (i.e., Cormack and Lehane grade 3-4), airway complications, and pulmonary aspiration. PRINCIPAL FINDINGS: A total of five trials (published from 2005 to 2018) were included, and all tracheal intubations were performed by anesthesiologists or nurse anesthetists with a video (n = 3) or Macintosh laryngoscope (n = 2) in the operating room. We found no significant difference in SFAIR (risk ratio [RR], 0.98; P = 0.37), incidence of poor laryngoscopic views (RR, 1.49; P = 0.21), and risk of sore throat (RR, 1.17; P = 0.73) between the two groups. Nevertheless, the intubation time on the first successful attempt was slightly longer (weighted mean difference = 4.40 sec, P = 0.002) and risk of hoarseness was higher (RR, 1.70; P = 0.03) in the CP group compared with in the non-CP group. The secondary outcome "pulmonary aspiration" was not analyzed because only one trial was available. CONCLUSION: The application of CP did not have a negative impact on the SFAIR or laryngoscopic view. Nevertheless, this maneuver may slightly prolong intubation time and increase the risk of postoperative hoarseness.

RéSUMé: OBJECTIF : Cette méta-analyse a pour but d'évaluer l'impact de l'application d'une pression cricoïdienne (PC) sur les résultats de l'intubation. SOURCE : Les bases de données électroniques (c.-à-d., MEDLINE, PubMed, Embase, et Cochrane review) ont été examinées de leur création jusqu'au 2 juin 2020 pour en tirer les études randomisées contrôlées évaluant les résultats d'intubation chez les patients adultes utilisant des approches laryngoscopiques avec ou sans application de PC (soit groupe PC et non-PC). Le critère d'évaluation principal était le taux d'intubations réussies à la première tentative, et les critères secondaires incluaient le temps d'intubation, l'incidence de mauvaises vues laryngoscopies (grades 3-4 de Cormack et Lehane), les complications au niveau des voies aériennes et l'aspiration pulmonaire. CONSTATATIONS PRINCIPALES : Cinq études au total (publiées entre 2005 et 2018) ont été incluses, et toutes les intubations trachéales ont été réalisées par des anesthésiologistes ou infirmiers anesthésistes à l'aide d'un vidéolaryngoscope (n = 3) ou d'une lame de Macintosh (n = 2) en salle d'opération. Nous n'avons trouvé aucune différence significative dans le taux d'intubations réussies à la première tentative (risque relatif [RR], 0,98; P = 0,37), dans l'incidence de mauvaises vues laryngoscopiques (RR, 1,49; P = 0,21) ou dans le risque de maux de gorge (RR, 1,17; P = 0,73) entre les deux groupes. En revanche, le temps d'intubation lors de la première tentative réussie était légèrement plus long (différence moyenne pondérée = 4,40 sec, P = 0,002) et le risque d'enrouement était plus élevé (RR, 1,70; P = 0,03) dans le groupe PC que dans le groupe non-PC. Le critère d'évaluation secondaire « aspiration pulmonaire ¼ n'a pas été analysé parce qu'une seule étude le mesurait. CONCLUSION : L'application de PC n'a pas eu d'impact négatif sur le taux d'intubations réussies à la première tentative ou la vue laryngoscopique. Par contre, cette manœuvre pourrait légèrement prolonger le temps d'intubation et augmenter le risque d'enrouement postopératoire.

Disproportional cardiovascular depressive effects of isoflurane: Serendipitous findings from a comprehensive re-visit in mice.

Employment of anesthetics, including isoflurane, though mandatory in animal experiments, is often regarded as a major limitation because results obtained with anesthetics may be different from those obtained under a conscious state. This study re-visits two issues related to the use of isoflurane. First, does isoflurane exert depression equally on all aspects of cardiovascular functions and their regulations? Second, is the circulatory supply of oxygen to brain tissues sufficient under isoflurane anesthesia? We determined in male C57BL/6J mice the temporal effects of 1.5% (vol/vol) isoflurane on blood pressure (BP), heart rate (HR), cardiac performance, baroreflex-mediated sympathetic vasomotor tone, cardiac vagal baroreflex, functional connectivity within the baroreflex neural circuits, carotid or cerebral blood flow, cortical tissue oxygen level, respiratory rate and blood gas. Over 150 min after exposure to 1.5% isoflurane, BP and HR were sustained at 71% and 79% of their awake levels amid a trend of progressive increase. Cardiac performance was within physiological ranges. Baroreflex-mediated sympathetic vasomotor tone gradually reversed from an 85% reduction toward the conscious level, alongside a parallel decrease in inhibitory connectivity between nucleus tractus solitarii (NTS) and rostral ventrolateral medulla. A decline in excitatory connectivity between NTS and nucleus ambiguus accompanied the decrease in cardiac vagal baroreflex. There were progressive increases in carotid or cerebral blood flow and tissue oxygen tension in cerebral cortex, alongside gradual hypoventilation, mild respiratory acidosis and hypercapnia. We conclude that, by eliciting disproportional depressive actions on cardiovascular functions and their regulations, which sustain circulatory supply of oxygen to brain tissues, 1.5% isoflurane is sufficient to maintain optimal cardiovascular functions in mice.

Adverse respiratory events with sevoflurane compared with desflurane in ambulatory surgery: A systematic review and meta-analysis.

BACKGROUND: An increasing number of studies have concluded that the number of adverse events in the upper airway caused by desflurane does not differ significantly from the number of adverse events caused by sevoflurane. The advantages of desflurane in ambulatory surgery should be reassessed. OBJECTIVES: The aim of this study was to compare adverse respiratory events and recovery outcomes in patients undergoing desflurane or sevoflurane-based anaesthesia in ambulatory surgery. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: A systematic search for eligible RCTs in PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect and Embase published up to June 2019. ELIGIBILITY CRITERIA: RCTs investigating the occurrence of adverse respiratory events, including airway irritation, stridor, coughing, respiratory distress and laryngospasm, emergence agitation, postoperative nausea and vomiting (PONV), time to eye opening and time to discharge from the operation room after desflurane or sevoflurane-based anaesthesia. RESULTS: Thirteen trials were included and analysed. A total of 634 patients were included in the desflurane group, and 633 patients in the sevoflurane group. The occurrence of respiratory complications was significantly higher with desflurane-based anaesthesia than with sevoflurane-based anaesthesia (Total n = 673, 20.0 vs. 12.8%, relative risk (RR) 1.59 (95% CI 1.15 to 2.20)) with low heterogeneity (I = 20%). There was no difference in the occurrence of emergence agitation (Total n = 626, 29.1 vs. 27.2%, RR 1.05 (95% CI 0.84 to 1.30)) or the incidence of PONV between the desflurane and sevoflurane groups (Total n = 989, 19.0 vs. 21.0%, RR 0.95 (95% CI 0.71 to 1.26)). Time to eye opening was significantly faster with desflurane than that with sevoflurane (Total n = 1072, mean difference = -3.32 min (95% CI -4.02 to -2.61)) with a substantial heterogeneity (I = 72.6%). There was no significant difference in the time to discharge from the operation room between the two groups (Total n = 1056, mean difference = -0.45 min (95% CI -5.89 to 4.99)). CONCLUSION: Despite recent reports that there is no significant difference in adverse respiratory events between desflurane and sevoflurane, a pooled analysis revealed that desflurane resulted in a higher rate than sevoflurane. Therefore, the consequences of desflurane should not be neglected and its airway irritant properties should be taken into account. TRIAL REGISTRATION: PROSPERO (CRD42019147939).

"A real-world evidence" in reduction of volatile anesthetics by BIS-guided anesthesia.

Many well-controlled clinical studies have shown that BIS-guided anesthesia could prevent intraoperative awareness and improve postoperative morbidity and mortality, by optimizing the amount of volatile anesthetics administered to patients. However, we questioned if the previously reported advantages of BIS-guided anesthesia in controlled studies would still apply in real-world settings. This retrospective study based on real-world settings clarified the role of BIS-guided anesthesia in reducing anesthetic consumption. We obtained anesthesia records from an electronic database of a medical center in southern Taiwan. A total of 6,713 cases were enrolled, where 1,324 cases receiving sevoflurane underwent BIS-guided anesthesia and 378 received desflurane; further, 3,819 receiving sevoflurane underwent standard anesthesia practice and 1,192 cases received desflurane. The median (25-75% interquartile values) of the average hourly consumption of sevoflurane or desflurane decreased significantly under BIS-guided anesthesia [10.5 (8.7-13.0) mL/h and 17.4 (13.7-21.1) mL/h, respectively] compared to that under standard anesthesia practice [11.4 (9.0-14.5) mL/h, and 20.2 (15.8-25.0), mL/h, respectively]. Furthermore, the average hourly consumption of these two volatile anesthetics varied inversely with age and anesthesia time in both groups. A significant reduction was found in the hourly consumption of volatile anesthetics in patients under BIS-guided anesthesia compared to standard anesthesia practice in different age groups or different anesthesia time. We concluded that BIS-guided anesthesia could reduce consumption of volatile anesthetics in real-world settings as well.

Baroreflex functionality in the eye of diffusion tensor imaging.

By applying diffusion tensor imaging (DTI) as a physiological tool to evaluate changes in functional connectivity between key brainstem nuclei in the baroreflex neural circuits of mice and rats, recent work has revealed several hitherto unidentified phenomena regarding baroreflex functionality. (1) The presence of robust functional connectivity between nucleus tractus solitarii (NTS) and nucleus ambiguus (NA) or rostral ventrolateral medulla (RVLM) offers a holistic view on the moment-to-moment modus operandi of the cardiac vagal baroreflex or baroreflex-mediated sympathetic vasomotor tone. (2) Under pathophysiological conditions (e.g. neurogenic hypertension), the disruption of functional connectivity between key nuclei in the baroreflex circuits is reversible. However, fatality ensues on progression from pathophysiological to pathological conditions (e.g. hepatic encephalopathy) when the functional connectivity between NTS and NA or RVLM is irreversibly severed. (3) The absence of functional connectivity between the NTS and caudal ventrolateral medulla (CVLM) necessitates partial rewiring of the classical neural circuit that includes CVLM as an inhibitory intermediate between the NTS and RVLM. (4) Sustained functional connectivity between the NTS and NA is responsible for the vital period between brain death and the inevitable cardiac death. (5) Reduced functional connectivity between the NTS and RVLM or NA points to inherent anomalous baroreflex functionality in floxed and Cre-Lox mice. (6) Disrupted NTS-NA functional connectivity in Flk-1 (VEGFR2) deficient mice offers an explanation for the hypertensive side-effect of anti-vascular endothelial growth factor therapy (anti-VEGF) therapy. These newly identified baroreflex functionalities revealed by DTI bear clinical and therapeutic implications.

Activation of spinal nociceptin receptors induces cardiovascular depression and antinociception in an independent manner in mice.

PURPOSE: The nociceptin receptor (NOP) was discovered in 1994 and was designated opioid-like receptor; activation of NOP leads to reduced neuronal excitability. Although suggested by the anatomical localization of NOP in brain or spinal cord, the cardiovascular or nociceptive effects of its endogenous ligand, nociceptin, are equivocal. Taking advantage from intrathecal application of nociceptin to simultaneously activate NOP on sympathetic preganglionic neurons in the intermediolateral column (IML) and superficial laminae of dorsal horn, we investigated whether the nociceptin-induced cardiovascular effects engage the participation of baroreflex, and whether the concurrently elicited changes in blood pressure and pain responses are interrelated. METHODS: NOPs in the thoracic spinal cord of ICR or C57BL/6 mice were identified with immunofluorescence staining and were activated through intrathecal administration of nocicetpin. The elicited changes in cardiovascular parameters and tail-flick nociceptive responses were measured. RESULTS: Positive immunoreactivity against NOP colocalized with neurons in the IML and superficial dorsal horn layers of thoracic spinal cord. Intrathecal administration of nociceptin (1, 2, or 5 nmol) elicited a significant and dose-dependent decrease in blood pressure or heart rate that was paralleled by reduced baroreflex-mediated sympathetic vasomotor tone and mirrored by augmented cardiac vagal baroreflex, alongside prolonged tail-flick latency with an efficacy of hypotension <<< antinociception. Coadministration of the specific NOP antagonist, UFP101 (10 nmol), blunted all nociceptin-elicited responses. However, restoring blood pressure to baseline level failed to affect the antinociceptive actions of nociceptin. CONCLUSION: Activation of thoracic spinal NOP in ICR and C57BL/6 mice induces blood pressure and heart rate by decreasing the sympathetic outflow of both arms of the baroreflex arc to the blood vessels and the heart, and the antinociceptive responses to nociceptin are independent of and disproportional to its cardiovascular actions.

Anomalous baroreflex functionality inherent in floxed and Cre-Lox mice: an overlooked physiological phenotype.

The last two decades have seen the emergence of Cre-Lox recombination as one of the most powerful and versatile technologies for cell-specific genetic engineering of mammalian cells. Understandably, the primary concerns in the practice of Cre-Lox recombination are whether the predicted genome has been correctly modified and the targeted phenotypes expressed. Rarely are the physiological conditions of the animals routinely examined because the general assumption is that they are normal. Based on corroborative results from radiotelemetric recording, power spectral analysis, and magnetic resonance imaging/diffusion tensor imaging in brain-derived neurotrophic factor-floxed mice, the present study revealed that this assumption requires amendment. We found that despite comparable blood pressure and heart rate with C57BL/6 or Cre mice under the conscious state, floxed and Cre-Lox mice exhibited diminished baroreflex-mediated sympathetic vasomotor tone and cardiac vagal baroreflex. We further found that the capacity and plasticity of baroreflex of these two strains of mice under isoflurane anesthesia were retarded, as reflected by reduced connectivity between the nucleus tractus solitarii and rostral ventrolateral medulla or nucleus ambiguus. The identification of anomalous baroreflex functionality inherent in floxed and Cre-Lox mice points to the importance of incorporating physiological phenotypes into studies that engage gene manipulations such as Cre-Lox recombination.NEW & NOTEWORTHY We established that anomalous baroreflex functionality is inherent in floxed and Cre-Lox mice. These two mouse strains exhibited diminished baroreflex-mediated sympathetic vasomotor tone and cardiac vagal baroreflex under the conscious state, retarded capacity and plasticity of baroreflex under isoflurane anesthesia, and reduced connectivity between key nuclei in the baroreflex neural circuits.

Endogenous nitric oxide derived from NOS I or II in thoracic spinal cord exerts opposing tonic modulation on sympathetic vasomotor tone via disparate mechanisms in anesthetized rats.

The sympathetic preganglionic neurons (SPN) in the thoracic spinal cord regulate vasomotor tone via norepinephrine released from sympathetic terminals and adrenal medulla. We assessed the hypothesis that nitric oxide synthase I (NOS I)- and NOS II-derived nitric oxide (NO) in the thoracic spinal cord differentially modulate sympathetic outflow and that the adrenal medulla may be involved in those modulatory actions. In Sprague-Dawley rats, NOS I immunoreactivity was distributed primarily in the perikaryon, proximal dendrites, or axons of SPN, and small clusters of NOS II immunoreactivity impinged mainly on the circumference of SPN. Intrathecal administration of 7-nitroindazole (7-NI), a specific NOS I antagonist, into the thoracic spinal cord significantly reduced arterial pressure, heart rate, and basal or baroreflex-mediated sympathetic vasomotor tone. On the other hand, intrathecal application of S-methylisothiourea (SMT), a specific NOS II antagonist, elevated arterial pressure with a transient reduction of heart rate, induced a surge of plasma norepinephrine, and reduced baroreflex-mediated but not basal sympathetic vasomotor tone. Bilateral adrenalectomy significantly exacerbated the cardiovascular responses to 7-NI but antagonized those to SMT. We conclude that both NOS I and NOS II are present in the thoracic spinal cord and are tonically active under physiological conditions. Furthermore, the endogenous NO generated by NOS I-containing SPN exerts a tonic excitatory action on vasomotor tone mediated by norepinephrine released from the adrenal medulla and sympathetic nerve terminals. On the other hand, NO derived from NOS II exerts a tonic inhibitory action on sympathetic outflow from the SPN that targets primarily the blood vessels.