Noscapine modulates hypoxia-induced angiogenesis and hemodynamics: Insights from a zebrafish model investigation.

We investigated the angiogenesis-modulating ability of noscapine in vitro using osteosarcoma cell line (MG-63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG-63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real-time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG-63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG-63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl2) induced hypoxic signaling molecules' gene expression in MG-63 cells and zebrafish embryos. Therefore, noscapine may prevent MG-63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

The impact of ultrasound-guided erector spinae plane block on hemodynamic stability and postoperative pain in patients undergoing modified radical mastectomy for breast cancer.

OBJECTIVE: Breast cancer, a prevalent global malignancy in women, necessitates a comprehensive treatment approach, with surgery playing a crucial role. Severe acute pain is common post-radical breast cancer surgery, emphasizing the significance of hemodynamic stability and postoperative pain control for optimal outcomes. This study evaluates the impact of ultrasound-guided erector spinae plane block (ESPB) on these parameters in ASA scores 1-2 patients undergoing modified radical breast cancer surgery with general anesthesia. PATIENTS AND METHODS: Forty-eight patients were divided into two groups: a general anesthesia group, with erector spinae plane block (GA+ESPB), and a control group receiving only general anesthesia (GA). Hemodynamic parameters were continuously monitored, and postoperative pain was assessed using the visual analog scale (VAS) at various time points. RESULTS: Ultrasound-guided ESPB effectively maintained hemodynamic stability and reduced postoperative pain in breast cancer surgery patients. Statistically significant differences were observed in heart rate, systolic and diastolic blood pressure, and mean arterial pressure between the GA and GA+ESPB groups at multiple time points (p < 0.05). VAS scores showed a significant interaction time*group (p < 0.001), with consistent differences between the groups at all time points (p ≤ 0.001). CONCLUSIONS: Ultrasound-guided ESPB application proved effective in preserving hemodynamic stability and managing postoperative pain in modified radical breast cancer surgery. The technique demonstrates promise in minimizing complications related to hemodynamic variations and postoperative pain, contributing to a comprehensive approach to breast cancer surgical treatment.

A dynamic brain network decomposition method discovers effective brain hemodynamic sub-networks for Parkinson's disease.

Objective.Dopaminergic treatment is effective for Parkinson's disease (PD). Nevertheless, the conventional treatment assessment mainly focuses on human-administered behavior examination while the underlying functional improvements have not been well explored. This paper aims to investigate brain functional variations of PD patients after dopaminergic therapy.Approach.This paper proposed a dynamic brain network decomposition method and discovered brain hemodynamic sub-networks that well characterized the efficacy of dopaminergic treatment in PD. Firstly, a clinical walking procedure with functional near-infrared spectroscopy was developed, and brain activations during the procedure from fifty PD patients under the OFF and ON states (without and with dopaminergic medication) were captured. Then, dynamic brain networks were constructed with sliding-window analysis of phase lag index and integrated time-varying functional networks across all patients. Afterwards, an aggregated network decomposition algorithm was formulated based on aggregated effectiveness optimization of functional networks in spanning network topology and cross-validation network variations, and utilized to unveil effective brain hemodynamic sub-networks for PD patients. Further, dynamic sub-network features were constructed to characterize the brain flexibility and dynamics according to the temporal switching and activation variations of discovered sub-networks, and their correlations with differential treatment-induced gait alterations were analyzed.Results.The results demonstrated that PD patients exhibited significantly enhanced flexibility after dopaminergic therapy within a sub-network related to the improvement of motor functions. Other sub-networks were significantly correlated with trunk-related axial symptoms and exhibited no significant treatment-induced dynamic interactions.Significance.The proposed method promises a quantified and objective approach for dopaminergic treatment evaluation. Moreover, the findings suggest that the gait of PD patients comprises distinct motor domains, and the corresponding neural controls are selectively responsive to dopaminergic treatment.

[Risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus]. / æœ‰è¡€æµåŠ¨åŠ›å­¦æ„ä¹‰çš„åŠ¨è„‰å¯¼ç®¡æœªé—­æ—©äº§å„¿å¸ƒæ´›èŠ¬æ²»ç–—å¤±è´¥çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Comparison of rocuronium priming vs. standard rapid sequence intubation technique in emergency department patients requiring intubation.

OBJECTIVE: In our study, we aimed to compare the effect of standard rapid sequence intubation protocol and the application of rocuronium priming technique on the procedure time and hemodynamic profile. METHODS: Patients who applied to the emergency department and needed rapid sequence intubation were included in our study, which we conducted with a randomized controlled design. Randomization in the study was made according to the order of arrival of the cases. Rapid sequence intubation was performed in the standard group. In the priming group, 10% of the rocuronium dose was administered approximately 3 min before the induction agent. Intubation time, amount of drug used, vital signs, and end-tidal CO2 level before and after intubation used to confirm intubation were recorded. RESULTS: A total of 52 patients were included in the study, of which 26 patients were included in the standard group and 26 patients in the priming group. While intubation time was 121.2±21.9 s in the standard group, it was calculated as 68.4±11.6 s in the priming group (p<0.001). While the mean arterial pressure was 58.3±26.6 mmHg in the standard group after intubation, it was 80.6±21.1 mmHg in the priming group (p=0.002). CONCLUSION: It was observed that priming with rocuronium shortened the intubation time and preserved the hemodynamic profile better. CLINICAL TRIAL REGISTRATION NUMBER: NCT05343702.

Association of Renin-Angiotensin-Aldosterone System Inhibitors With Clinical Outcomes, Hemodynamics, and Myocardial Remodeling Among Patients With Advanced Heart Failure on Left Ventricular Assist Device Support.

BACKGROUND: We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. METHODS AND RESULTS: A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P=0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P=0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively). CONCLUSIONS: RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

Association between baseline hemodynamic indices, cardiotoxicity risk, and survival in women with breast cancer.

BACKGROUND: The outcome of breast cancer (BrCa) women monitored by low-dose equilibrium radionuclide angiography (ERNA) remains challenging to predict. AIM: This study aims to determine whether heart rate (HR)/blood pressure (BP) ratio-based indexes, previously confirmed to predict outcomes of various diseases, also predict BrCa-therapy-related cardiotoxicity and survival. METHODS: Predictors of cardiotoxicity and survival were determined among pre-therapy variables, including shock index ([SI HR/systolic BP) and age-adjusted SI (ASI), in a female BrCa cohort with normal baseline ERNA-left ventricular ejection fraction (LVEF). RESULTS: We included 274 women with a median age of 54.8 (interquartile range: 45.5-65.4) years, 271 treated with anthracyclines and 96 with trastuzumab. During a median follow-up of 25.9 (18.6-33.5) months, 31 women developed cardiotoxicity (LVEF: <50% and ≥10% drop from baseline), and 25 died. Baseline ASI was a multivariate predictor (p < 0.001) of (i) cardiotoxicity, in association with trastuzumab treatment (p = 0.010), and LV end-diastolic volume (p = 0.001) and (ii) survival, in association with metastasis (p < 0.001) and estimated glomerular filtration rate (p = 0.008). Cardiotoxicity poorly impacted survival (p = 0.064). The 36-month cardiotoxicity and mortality rates were markedly higher for patients in the upper half of baseline ASI values (ASI: >30 years min-1.mmHg-1, 16.5% and 20.7%, respectively) than in the lower half (7.6% and 4.5%, respectively, both p < 0.05). CONCLUSIONS: In BrCa women with normal baseline ERNA-LVEF, HR/BP ratio-based indexes unmask hemodynamic profiles associated with increased cardiotoxicity risk and decreased survival, highlighting the need for a comprehensive assessment of cardiac- and vascular-related risks in BrCa women monitored by ERNA. CONDENSED ABSTRACT: In a cohort of 274 women BrCa women who were monitored by ERNA for potentially cardiotoxic drugs (anthracyclines or trastuzumab) and who had no history of cardiac disease and a normal left ventricular ejection fraction before treatment, baseline indexes based on HR/BP ratios unmask hemodynamic profiles strongly associated with an increased risk of cardiotoxicity and subsequently decreased survival. Although further validations in other cohorts are needed, these findings highlight the need for a more comprehensive assessment of the cardiac- and vascular-related risk in BrCa women monitored by ERNA.

Acute High-Output Heart Failure with Pulmonary Hypertension and Severe Liver Injury Caused by Amlodipine Poisoning: A Case Report.

Acute high-output heart failure (HOHF) with pulmonary hypertension and liver injury caused by amlodipine poisoning is very rare. We report a 52-year-old woman who suffered from severe shock after an overdose of amlodipine. Hemodynamic monitoring showed that while her left ventricular systolic function and cardiac output were elevated, her systemic vascular resistance decreased significantly. At the same time, the size of her right heart, her central venous pressure, and the oxygen saturation of her central venous circulation all increased abnormally. The patient's circulatory function and right ventricular dysfunction gradually improved after large doses of vasopressors and detoxification measures. However, her bilirubin and transaminase levels increased significantly on hospital day 6, with a CT scan showing patchy, low-density areas in her liver along with ascites. After liver protective treatment and plasma exchange, the patient's liver function gradually recovered. A CT scan 4 months later showed all her liver abnormalities, including ascites, had resolved. The common etiologies of HOHF were excluded in this case, and significantly reduced systemic vascular resistance caused by amlodipine overdose was thought to be the primary pathophysiological basis of HOHF. The significant increase in venous return and pulmonary blood flow is considered to be the main mechanism of right ventricular dysfunction and pulmonary hypertension. Hypoxic hepatitis caused by a combination of hepatic congestion and distributive shock may be the most important factors causing liver injury in this patient. Whether amlodipine has other mechanisms leading to HOHF and pulmonary hypertension needs to be further studied. Considering the significant increase of right heart preload, aggressive fluid resuscitation should be done very cautiously in patients with HOHF and shock secondary to amlodipine overdose.

Effects of furosemide, acetazolamide and amiloride on renal cortical and medullary tissue oxygenation in non-anaesthetised healthy sheep.

It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the impact of clinically used diuretic drugs on the renal cortical and medullary microcirculation is unclear. Therefore, we examined the effects of three commonly used diuretics, at clinically relevant doses, on renal cortical and medullary perfusion and oxygenation in non-anaesthetised healthy sheep. Merino ewes received acetazolamide (250 mg; n = 9), furosemide (20 mg; n = 10) or amiloride (10 mg; n = 7) intravenously. Systemic and renal haemodynamics, renal cortical and medullary tissue perfusion and P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ , and renal function were then monitored for up to 8 h post-treatment. The peak diuretic response occurred 2 h (99.4 ± 14.8 mL/h) after acetazolamide, at which stage cortical and medullary tissue perfusion and P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ were not significantly different from their baseline levels. The peak diuretic response to furosemide occurred at 1 h (196.5 ± 12.3 mL/h) post-treatment but there were no significant changes in cortical and medullary tissue oxygenation during this period. However, cortical tissue P O 2 ${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ fell from 40.1 ± 3.8 mmHg at baseline to 17.2 ± 4.4 mmHg at 3 h and to 20.5 ± 5.3 mmHg at 6 h after furosemide administration. Amiloride did not produce a diuretic response and was not associated with significant changes in cortical or medullary tissue oxygenation. In conclusion, clinically relevant doses of diuretic agents did not improve regional renal tissue oxygenation in healthy animals during the 8 h experimentation period. On the contrary, rebound renal cortical hypoxia may develop after dissipation of furosemide-induced diuresis.

Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity.

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.

Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. OBJECTIVES: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. METHODS: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. RESULTS: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. CONCLUSIONS: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Comparison of remimazolam-based and propofol-based total intravenous anesthesia on hemodynamics during anesthesia induction in patients undergoing transcatheter aortic valve replacement: a randomized controlled trial.

PURPOSE: This study aimed to compare the hemodynamic effects of remimazolam- and propofol-based total intravenous anesthesia in patients who underwent transcatheter aortic valve replacement. METHODS: This was a single-center, single-blind, randomized controlled trial set at Nara Medical University, Kashihara, Japan. We included 36 patients aged ≥ 20 years scheduled to undergo elective transfemoral transcatheter aortic valve replacement (TAVR) under general anesthesia. The participants were randomly assigned to the remimazolam and propofol groups (n = 18 each). Remimazolam- or propofol-based total intravenous anesthesia was initiated at 12 mg/kg/min or 2.5 mcg/mL via target-controlled infusion, respectively, along with remifentanil. After confirming the loss of consciousness, the administration rate was adjusted using electroencephalographic monitoring. The primary outcome was the rate of arterial hypotension, defined as a mean arterial pressure < 60 mmHg, from anesthesia induction until the beginning of the surgical incision. The total doses of ephedrine and phenylephrine were also assessed. RESULTS: During anesthesia induction, the arterial hypotension rates were 11.9% and 21.6% in the remimazolam and propofol groups, respectively (P = 0.01). The total dose of ephedrine was higher in the propofol group (14.4 mg) than in the remimazolam group (1.6 mg) (P < 0.001); however, the total dose of phenylephrine was not significantly different between the two groups (propofol 0.31 mg vs. remimazolam: 0.17 mg, P = 0.10). CONCLUSION: Remimazolam-based total intravenous anesthesia resulted in a lower hypotension rate than propofol-based total intravenous anesthesia during induction in patients undergoing TAVR. Remimazolam-based total intravenous anesthesia can be used safely during anesthetic induction in patients with severe aortic stenosis.

Haemodynamic effects of labetalol in isoflurane-anaesthetized dogs that received dexmedetomidine: A randomized clinical trial.

OBJECTIVE: To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 20 healthy client-owned dogs undergoing ovariohysterectomy. METHODS: Each dog received dexmedetomidine (5 µg kg-1) and methadone (0.2 mg kg-1) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO2) was also recorded. Prior to surgery, animals received either 0.1 mg kg-1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests. RESULTS: Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Labetalol at a dose of 0.1 mg kg-1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects.

Application Value of Sevoflurane Combined with Brachial Plexus Block in Children with Humeral Fracture Surgery and its Effect on Hemodynamics: A Clinical and Anatomical Study

SUMMARY: To observe the effect of sevoflurane combined with brachial plexus block (BPB) in children with humeral fracture surgery and its effect on hemodynamics. 84 children who received surgical treatment of humeral fracture in our hospital from September 2019 to September 2022 were selected. According to different anesthesia methods, the children were divided into control group and study group. The control group only received laryngeal mask sevoflurane; the study group received laryngeal mask sevoflurane combined with BPB. The operation situation, hemodynamic indexes, stress level, pain and adverse reactions of children was observed. The postoperative awakening time in the study group was lower than control group, the postoperative pain onset time in the study group was higher than control group (P0.05). Postoperative 2h, the levels of serum cortisol, b-endorpin, norepinephrine and epinephrine in the study group were lower than control group (P0.05). Sevoflurane combined with BPB is helpful to shorten the postoperative awakening time of children with humeral fracture, reduce the degree of postoperative pain, improve hemodynamics, and reduce stress response, and has good safety.

El objetivo fue observar el efecto del sevoflurano combinado con bloqueo del plexo braquial (BPB) en niños con cirugía de fractura de húmero y su efecto sobre la hemodinámica. Se seleccionaron 84 niños que recibieron tratamiento quirúrgico de fractura de húmero en nuestro hospital desde septiembre de 2019 hasta septiembre de 2022. Según diferentes métodos de anestesia, los niños se dividieron en grupo control y grupo de estudio. El grupo control solo recibió sevoflurano en mascarilla laríngea; el grupo de estudio recibió sevoflurano con mascarilla laríngea combinado con BPB. Se observó la situación operatoria, índices hemodinámicos, nivel de estrés, dolor y reacciones adversas de los niños. El tiempo hasta el despertar postoperatorio en el grupo de estudio fue menor que el del grupo control, el tiempo de aparición del dolor postoperatorio en el grupo de estudio fue mayor que el del grupo control (P0,05). A las 2 horas postoperatorias, los niveles séricos de cortisol, β-endorfina, norepinefrina y epinefrina en el grupo de estudio fueron más bajos que los del grupo control (P 0,05). El sevoflurano combinado con BPB es útil para acortar el tiempo de despertar del posoperatorio de los niños con fractura de húmero, reduce el grado de dolor postoperatorio, mejora la hemodinámica y reduce la respuesta al estrés, además de tener buena seguridad.

Cambios Hemodinámicos Asociados a Exodoncias de Terceros Molares Inferiores con el Uso de Articaína 4 % y/o Lidocaína 2 %: Una revisión sistemática / Hemodynamic Changes Associated with Lower Third Molar Extractions with the Use of Articaine 4 % and/or Lidocaine 2 %: A systematic Review

La exodoncia de los terceros molares inferiores es uno de los procedimientos clínicos más comunes en el cual el control del dolor mediante el bloqueo anestésico del nervio alveolar inferior, bucal y lingual resulta ser fundament al y la manera más común de hacerlo es mediante la infiltración de soluciones de anestesia local. Entre ellos la lidocaína y articaína son algunos de los más comunes y pueden estar asociado a vasoconstrictores como la epinefrina que puede provocar aumento de la presión arterial y frecuencia cardíaca razón por la cual se hace necesario la monitorización de cambios hemodinámicos durante la cirugía. Describir los cambios hemodinámicos asociados al uso de lidocaína al 2 % y/ o articaína al 4 % en la presión sistólica y diastólica, frecuencia cardiaca y saturación parcial de oxígeno en relación a distintos tiempos operatorios. Se realizó una revisión sistemática en las bases de datos de PubMed, SCOPUS, Web of Science y Sciencedirect. Se analizaron 7 ensayos clínicos controlados en los que utilizaron articaína al 4 % y/o lidocaína al 2 % con epinefrina al 1:100,000 y/o 1:200,000 en volúmenes de 1,8 a 5,4 mL, en los cuales evaluaron la presión sistólica y diastólica, frecuencia cardiaca y saturación parcial de oxígeno en distintos tiempos de la cirugía. Si bien hubo cambios en PAS, PAD, FC y SPO2, todas se mantuvieron dentro de rangos normales bajo el uso de articaína al 4 % y lidocaína al 2 % con epinefrina 1:100,000 y/o 1:200,000 a volúmenes de 1,8 a 5,4mL medidas a distintos tiempos operatorios.

The extraction of lower third molars is one of the most common clinical procedures in which pain control through anesthetic blockade of the lower alveolar, buccal and lingual nerves turns out to be essential and the most common way to do it is through the infiltration of solutions of local anesthesia. Among them, lidocaine and articaine are some of the most common and may be associated with vasoconstrictors such as epinephrine, which can cause an increase in blood pressure and heart rate, which is why it is necessary to monitor hemodynamic changes during surgery. To describe the hemodynamic changes associated with the use of 2 % lidocaine and/or 4 % articaine in systolic and diastolic pressure, heart rate and partial oxygen saturation in relation to different operative times. A systematic review was carried out in the PubMed, SCOPUS, Web of Science and Sciencedirect databases. Seven controlled clinical trials were analyzed in which 4 % articaine and/or 2 % lidocaine were used with epinephrine at 1:100,000 and/or 1:200,000 in volumes of 1,8 to 5,4 mL, in which systolic pressure was evaluated. and diastolic, heart rate and partial oxygen saturation at different times of surgery. Although there were changes in SBP, DBP, HR and SPO2, all remained within normal ranges under the use of 4 % articaine and 2 % lidocaine with epinephrine 1:100,000 and/or 1:200,000 at volumes of 1,8 to 5 .4mL measured at different operative times.

Local Anaesthetics Combined with Vasoconstrictors in Controlled Hypertensive Patients Undergoing Dental Procedures: Systematic Review and Meta-Analysis / Uso de Anestésicos Locales con Vasoconstrictor en Pacientes con Hipertensión Controlada Durante la Atención Odontológica: Una Revisión Sistemática y Metaanálisis

The aim of this systematic review is to assess the safety of local anaesthetics (LA) combined with vasoconstrictors (VC) for patients with controlled hypertension undergoing dental procedures. A comprehensive search strategy were used to identify all relevant randomized controlled trials (RCTs) that evaluated the effect of LA combined with VC. All searches covered the period from 1990 to February 2021. We performed a meta-analysis using random-effect models and assessed overall certainty in evidence using GRADE approach. Our search strategy yielded 1262 references. Finally, seven randomised trials were included, but only three were included in the meta-analysis. The use of LA with VC may result in little to no difference in the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), but the certainty of the evidence was assessed as low. Death, stroke, acute myocardial infarction, need for hospitalization, pain and bleeding were not reported by the included studies. The hemodynamic changes using VC do not imply an increased risk of occurrence of adverse cardiovascular events. The use of VC could even be recommendable considering their multiple advantages.

El objetivo de esta revisión sistemática es evaluar la seguridad del uso de anestésicos locales (AL) combinados con vasoconstrictor (VC) en pacientes con hipertensión controlada durante procedimientos dentales. Se realizó una estrategia de búsqueda para identificar todos los estudios clínicos aleatorizados (ECA) relevantes que evaluaban el efecto del AL combinado con VC. Todos los estudios fueron del periodo entre 1990 a febrero del 2021. Se realizó un meta-análisis usando modelos de efecto aleatorizado y una revisión de la certeza de la evidencia usando el método GRADE. Nuestra estrategia de búsqueda arrojó 1262 referencias. Finalmente, siete estudios clínicos aleatorizados fueron incluidos, de los cuales tres fueron incluidos en el meta-análisis. El uso de AL con VC produce una pequeña a ninguna diferencia en el pulso cardiaco, presión sistólica y diastólica, pero la certeza de la evidencia fue baja. Muerte, infarto agudo al miocardio, accidente cerebrovascular, necesidad de hospitalización, dolor y hemorragia no fueron reportados en los estudios incluidos. Los cambios hemodinámicos en el uso de VC no implican un aumento de riesgo de ocurrencia de efectos adversos cardiovasculares. El uso de VC puede ser recomendable considerando sus múltiples ventajas.

Preoperative sedation in children with congenital heart disease: 50% and 95% effective doses, hemodynamic effects, and safety of intranasal dexmedetomidine.

STUDY OBJECTIVE: To determine the 50% and 95% effective doses (ED50 and ED95, respectively), hemodynamic effects, and safety of intranasal dexmedetomidine for preoperative sedation in pediatric patients with congenital heart disease (CHD) with a left-to-right shunt. DESIGN: Double-blind sequential allocation trial. SETTING: Pediatric preoperative waiting area. PATIENTS: 86 pediatric patients ASA physical status II-III scheduled for cardiac surgery, aged1-month to 6-years-old with left-to-right type CHD. INTERVENTIONS: Children were divided into three groups according to age: infants (1 month-1 year), toddlers (1-3 years), and preschoolers (3-6 years). The first patient in all groups received intranasal dexmedetomidine (2 µg/kg), using the up-and-down Dixon method, and the and the next patient's dose was dependent on the previous patient's response. MEASUREMENTS: Assessment using the Modified Observer's Assessment of Alertness/Sedation Scale and the Mask Acceptance Scale was performed before and every 5 min after treatment. Pulse oxygen saturation and heart rate were recorded at baseline, at 10-min intervals, and after admission to the operating room. Systolic pulmonary artery pressure was measured before anesthesia induction. MAIN RESULTS: The respective ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for preoperative sedation using intranasally administered dexmedetomidine were 3.1 (2.8-3.3) and 3.5 (3.3-4.0) µg/kg for infants; 3.4 (3.2-3.6) and 3.9 (3.7-4.4) µg/kg for toddlers; and 2.4 (2.2-2.6) and 2.9 (2.6-3.3) µg/kg for preschoolers. ED50 was lower for preschoolers than for toddlers (p < 0.001) and infants (p = 0.044). No obvious difference in ED50 was found between infants and toddlers. There was no significant difference in sedation onset time among the groups, and no adverse events were observed during sedation in all patients. CONCLUSIONS: Intranasal dexmedetomidine can be safety used for preoperative sedation in children with CHD and is effective for sedation when dosed appropriately. Trial registrationclinicaltrials.gov (ChiCTR2100047472); registered 20 June 2021.

Effect of Clemastine Fumarate on Perioperative Hemodynamic Instability Mediated by Anaphylaxis During Cardiopulmonary Bypass Surgery.

BACKGROUND Perioperative hemodynamic instability mediated by anaphylaxis is a life-threatening complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to evaluate the effect of clemastine fumarate in this specific patient population. MATERIAL AND METHODS We enrolled 100 participants who met the inclusion criteria and randomly allocated them to the treatment group and the placebo group. Participants in the treatment group and the placebo group were treated separately with an injection of clemastine fumarate and saline, respectively. Plasma histamine concentration and blood pressure were quantified at 5 timepoints during the perioperative period, and differences between the 2 groups were assessed by repeated-measures ANOVA. The postoperative complications and in-hospital mortality also were evaluated. All participants were followed up for 7 days after cardiac surgery. RESULTS Plasma histamine concentrations increased in both groups but were statistically significantly lower in the treatment group during the perioperative period (P=0.007). Diastolic blood pressure (P=0.014) and mean arterial pressure (P=0.024) in the treatment group were significantly higher than in the placebo group during the perioperative period. The coefficients of variation for systolic (13.9±4.2% vs 17.2±4.4%, P<0.01) and diastolic (12.9±4.9% vs 15.3±5.2%, P=0.02) blood pressure were significantly lower in the treatment group compared with the placebo group. CONCLUSIONS Pretreatment with clemastine fumarate restrains the increase in histamine concentration and provides safer hemodynamics in patients undergoing cardiac surgery with CPB.