The potential anti-arrhythmic effect of SGLT2 inhibitors.

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) were initially recommended as oral anti-diabetic drugs to treat type 2 diabetes (T2D), by inhibiting SGLT2 in proximal tubule and reduce renal reabsorption of sodium and glucose. While many clinical trials demonstrated the tremendous potential of SGLT2i for cardiovascular diseases. 2022 AHA/ACC/HFSA guideline first emphasized that SGLT2i were the only drug class that can cover the entire management of heart failure (HF) from prevention to treatment. Subsequently, the antiarrhythmic properties of SGLT2i have also attracted attention. Although there are currently no prospective studies specifically on the anti-arrhythmic effects of SGLT2i. We provide clues from clinical and fundamental researches to identify its antiarrhythmic effects, reviewing the evidences and mechanism for the SGLT2i antiarrhythmic effects and establishing a novel paradigm involving intracellular sodium, metabolism and autophagy to investigate the potential mechanisms of SGLT2i in mitigating arrhythmias.

A phase I thorough QT/QTc study evaluating therapeutic and supratherapeutic doses of avacopan in healthy participants.

This phase I thorough QTc, double-blind, randomized, placebo- and positive-controlled, parallel group, multiple-dose study evaluated avacopan's effect on cardiac repolarization using concentration-QTc (C-QTc) as the primary analysis. Avacopan 30 mg b.i.d. (therapeutic dose) was administered orally on days 1 through 7 followed by avacopan 100 mg b.i.d. (supratherapeutic dose) on days 8 through 14 in 29 healthy participants. Moxifloxacin 400 mg and placebo were administered on days 1 and 15 in a nested crossover design for assay sensitivity in separate cohorts to 28 participants. Time-matched plasma concentrations and up to 10 replicate ECGs were obtained on prespecified days at baseline and postdose on days 1, 7, 14, and 15. The mean change from baseline on QTcF for avacopan (-5.5 to 3.5 ms) was similar to placebo (-6.9 to 1.4 ms) across days 1, 7, and 14. The mean effect on ΔΔQTcF (90% CI) was estimated as 1.5 ms (-0.17 to 3.09) and 0.8 ms (-2.41 to 4.05) for 30 and 100 mg avacopan b.i.d. treatments, respectively. Based on the C-QTc analysis, avacopan's effect on ΔΔQTcF >10 ms can be excluded within the observed plasma concentration range of up to ~1220 and ~335 ng/mL for avacopan and active major metabolite, M1, respectively. The estimated population slopes showed a shallow relationship, which was not statistically significant. There was no clinically meaningful effect of avacopan on heart rate or cardiac conduction (PR and QRS intervals). Avacopan appeared to be generally well tolerated in this study population.

Consumer wearable devices for evaluation of heart rate control using digoxin versus beta-blockers: the RATE-AF randomized trial.

Consumer-grade wearable technology has the potential to support clinical research and patient management. Here, we report results from the RATE-AF trial wearables study, which was designed to compare heart rate in older, multimorbid patients with permanent atrial fibrillation and heart failure who were randomized to treatment with either digoxin or beta-blockers. Heart rate (n = 143,379,796) and physical activity (n = 23,704,307) intervals were obtained from 53 participants (mean age 75.6 years (s.d. 8.4), 40% women) using a wrist-worn wearable linked to a smartphone for 20 weeks. Heart rates in participants treated with digoxin versus beta-blockers were not significantly different (regression coefficient 1.22 (95% confidence interval (CI) -2.82 to 5.27; P = 0.55); adjusted 0.66 (95% CI -3.45 to 4.77; P = 0.75)). No difference in heart rate was observed between the two groups of patients after accounting for physical activity (P = 0.74) or patients with high activity levels (≥30,000 steps per week; P = 0.97). Using a convolutional neural network designed to account for missing data, we found that wearable device data could predict New York Heart Association functional class 5 months after baseline assessment similarly to standard clinical measures of electrocardiographic heart rate and 6-minute walk test (F1 score 0.56 (95% CI 0.41 to 0.70) versus 0.55 (95% CI 0.41 to 0.68); P = 0.88 for comparison). The results of this study indicate that digoxin and beta-blockers have equivalent effects on heart rate in atrial fibrillation at rest and on exertion, and suggest that dynamic monitoring of individuals with arrhythmia using wearable technology could be an alternative to in-person assessment. ClinicalTrials.gov identifier: NCT02391337 .

PERSONIFICATION OF ANTIHYPERTENSIVE THERAPY IN ISCHEMIC CEREBRAL STROKE.

The purpose of the study is to optimize monitoring and personalize antihypertensive therapy in patients with severe ischemic cerebral stroke (ICS). We examined 37 patients with ICS, average age 74,1±1,3 years, who received treatment in intensive care wards of the stroke department with general neurology beds of the Municipal Non-Profit Enterprise "City Hospital № 9" of the Zaporizhzhia City Council. There were 16 men (43,2%), average age 71,9±2,1 years; women - 21 (56,8%), average age 75,8±1.6 years. Personification of antihypertensive therapy for severe ICS was carried out based on the etiology of hypertensive hemodynamic disorders: hyperkinetic type of arterial hypertension (Cardiac index ≥ 3,80 L×min-1×m-2) or hypokinetic type of arterial hypertension (Cardiac index ≤ 2,98 L×min-1×m-2). In patients with severe ICS and hyperkinetic type of arterial hypertension, initial hemodynamic parameters were characterized by Mean arterial pressure (MAP) of 111,4 ± 1,4 mm Hg; Heart rate (HR) of 107,2±1,6 min; Cardiac index (CI) 6,74±0,27 L×min-1×m-2; the Total peripheral vascular resistance (TPVR) is 674±36 dyn×sec-1×cm-5. For the purpose of antihypertensive correction of the hyperkinetic type of arterial hypertension (CI ≥ 3,80 L×min-1×m-2), a solution of Magnesium Sulfate was used intravenously at a dose of 2500-5000 mg×day-1 in combination with Bisoprolol 5-10 mg×day-1 orally. This made it possible to stabilize hemodynamic parameters by the end of intensive therapy within the limits of eukinetic values: MAP 95,2±1,5 mm Hg (p<0,05); HR 81,9±1,5 min (p<0,05); CI 3,60±0,15 L×min-1×m-2 (p<0,05); TPVR is 1079±58 dyn×sec-1×cm-5 (p<0,05). In patients with severe ICS and hypokinetic type of arterial hypertension, initial hemodynamic parameters were characterized by MAP of 117,7±2,8 mm Hg; HR of 76,7±1,5 min; CI 2,74±0,18 L×min-1×m-2; TPVR is 1754±123 dyn×sec-1×cm-5. For the purpose of antihypertensive correction of the hypokinetic type of arterial hypertension (CI≤2,98 L×min-1×m-2), a solution of Ebrantil was used intravenously as a bolus of 1,25-2,5 mg with a further infusion of 5-40 mg×hour-1. This made it possible to stabilize hemodynamic parameters by the end of intensive therapy within the limits of eukinetic values: MAP 92,7 ± 1,7 mm Hg (p<0,05); HR 81,4 ± 0,9 min (p<0,05); CI 3,65±0,16 L×min-1×m-2 (p<0,05); TPVR is 1036±46 dyn×sec-1×cm-5 (p<0,05).

[Calcium Dibutyryl Adenosine Cyclophosphate Enhances the Effect of Metoprolol in Treating Older Adults With Heart Failure Combined With Arrhythmia]. / äºŒä¸é °çŽ¯ç£·è ºè‹·é’™å¯å¢žå¼ºç¾Žæ‰˜æ´›å°”å¯¹è€å¹´å¿ƒåŠ›è¡°ç«­åˆå¹¶å¿ƒå¾‹å¤±å¸¸æ‚£è€ çš„æ²»ç–—æ•ˆæžœ.

Objective: To explore the effect and safety of calcium dibutyryl adenosine cyclophosphate (dbcAMP-Ca) combined with metoprolol in the treatment of older adults with heart failure combined with arrhythmia. Methods: A total of 102 elderly patients with heart failure combined with arrhythmia were enrolled in our hospital between February 2021 and April 2023. The list of patients enrolled was entered into a random database by independent staffs not involved in the study and random assignment sequences were generated by the SAS9.4 software. Then, the 102 elderly patients were divided into a control group ( n=51) and an experimental group ( n=51). Patients in the control group were given metoprolol at an initial dose of 6.25 mg/d, which was gradually increased to the target dose of 25 mg/d. Patients in the experimental group were given 40 mg of dbcAMP-Ca once a day via intravenous drip in addition to the treatment given to the control group. Both groups were treated for 4 weeks. The rate of effective response to clinical treatment (the number of cases achieving significant effects and those achieving some effects divided by the total number of cases in the group) was defined as the main outcome index. Secondary indexes included cardiac function, heart rate variability, exercise ability, hemorheology, myocardial injury indexes, inflammatory indexes, and the occurrence of adverse reactions. Results: The rate of effective response to clinical treatment was higher in the experimental group than that in the control group (94.12% [48/51] vs. 78.43% [40/51], P<0.05). After treatment, the left ventricular end-diastolic and end-systolic dimensions (LVEDD and LVESD) and the interventricular septal thickness (IVS) were lower in the experimental group than those in the control group, while the left ventricular ejection fraction (LVEF) and the stroke volume (SV) were higher in the experimental group than those in the control group ( P<0.05). In terms of heart rate variability after treatment, the standard deviation of all the normal-to-normal intervals/the average of all the normal-to-normal intervals (SDNN/SDANN), the percentage of NN50 in the total number of normal-to-normal intervals (PNN50%), and the root mean square of the differences between adjacent normal-to-normal intervals/root mean square differences of successive R-R intervals (RMSSD) were higher in the experimental group than those in the control group ( P<0.05). In terms of exercise capacity after treatment, the subjects in the experimental group covered more distance in the 6-min walk test than those in the control group did ( P<0.05). In terms of the hemorheology indexes after treatment, the levels of platelet aggregation rate (PAgT), fibrinogen (FIB), erythrocyte sedimentation rate (ESR), and whole blood viscosity (ηb) were lower in the experimental group than those in the control group ( P<0.05). In terms of the myocardial injury indexes after treatment, the levels of serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) and cardiac troponin I (cTnI) were lower in the experimental group than those in the control group, while the levels of insulin-like growth factor 1 (IGF-1) and cardiotrophin 1 (CT-1) were higher in the experimental group than those in the control group ( P<0.05). In terms of the inflammatory indexes after treatment, the levels of interleukin-6 (IL-6), high-sensitive C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) were lower in the experimental group than those in the control group ( P<0.05). The incidence of adverse reactions in the experimental group (9.80%) and that in the control group (7.84%) were comparable ( P>0.05). Conclusion: The use of dbcAMP-Ca in addition to metoprolol can effectively improve cardiac function, heart rate variability, and exercise tolerance, while inhibiting inflammatory response in elderly patients with heart failure combined with arrhythmia, with high medication safety. The combination medication shows better safety and therapeutic effects than those of metoprolol used alone.

Zolpidem-triggered atrial fibrillation in a patient with cardiomyopathy: a case report.

BACKGROUND: Zolpidem is a non-benzodiazepine hypnotic widely used to manage insomnia. Zolpidem-triggered atrial fibrillation (AF) in patients with cardiomyopathy has never been reported before. CASE PRESENTATION: A 40-year-old man with Duchenne muscular dystrophy-related cardiomyopathy attempted suicide and developed new-onset AF after zolpidem overdose. One year before admission, the patient visited our clinic due to chest discomfort and fatigue after daily walks for 1 month; both electrocardiography (ECG) and 24-hour Holter ECG results did not detect AF. After administration of cardiac medication (digoxin 0.125 mg/day, spironolactone 40 mg/day, furosemide 20 mg/day, bisoprolol 5 mg/day, sacubitril/valsartan 12/13 mg/day), he felt better. AF had never been observed before this admission via continuous monitoring during follow-up. Sixteen days before admission, the patient saw a sleep specialist and started zolpidem tartrate tablets (10 mg/day) due to insomnia for 6 months; ECG results revealed no significant change. The night before admission, the patient attempted suicide by overdosing on 40 mg of zolpidem after an argument, which resulted in severe lethargy. Upon admission, his ECG revealed new-onset AF, necessitating immediate cessation of zolpidem. Nine hours into admission, AF spontaneously terminated into normal sinus rhythm. Results from the ECG on the following days and the 24-hour Holter ECG at 1-month follow-up showed that AF was not detected. CONCLUSIONS: This study provides valuable clinical evidence indicating that zolpidem overdose may induce AF in patients with cardiomyopathy. It serves as a critical warning for clinicians when prescribing zolpidem, particularly for patients with existing heart conditions. Further large-scale studies are needed to validate this finding and to explore the mechanisms between zolpidem and AF.

Impact of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality based active shooter training drill.

Ingestion of L-theanine and L-tyrosine has been shown to reduce salivary stress biomarkers and improve aspects of cognitive performance in response to stress. However, there have been no studies to concurrently examine the impact of both L-theanine and L-tyrosine ingestion during a mental stress challenge (MSC) involving a brief cognitive challenge and a virtual reality based active shooter training drill. Thus, the purpose of this study was to determine the impact of ingestion of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality active shooter drill and cognitive challenge. The cognitive challenge involved a Stroop challenge and mental arithmetic. Eighty subjects (age = 21 ± 2.6 yrs; male = 46; female = 34) were randomly assigned L-tyrosine (n = 28; 2000 mg), L-theanine (n = 25; 200 mg), or placebo (n = 27) prior to MSC exposure. Saliva samples, state-anxiety inventory (SAI) scales, and heart rate (HR) were collected before and after exposure to the MSC. Saliva was analyzed for stress markers α-amylase (sAA) and secretory immunoglobulin A (SIgA). The MSC resulted in significant increases in sAA, SIgA, HR, and SAI. Ingestion of L-theanine and L-tyrosine did not impact markers of stress. However, the L-tyrosine treatment demonstrated significantly lower missed responses compared to the placebo treatment group during the Stroop challenge. These data demonstrate that ingestion of L-theanine or L-tyrosine does not impact markers of stress in response to a MSC but may impact cognitive performance. This study was pre-registered as a clinical trial ("Impact of supplements on stress markers": NCT05592561).

Does a broad-spectrum cannabidiol supplement improve performance in a 10-min cycle ergometer performance-test?

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid which has been proposed to possess anti-inflammatory and analgesic properties. Given the potential for perceptions of pain to limit exercise performance, the aim of the present study was to investigate if 3 weeks of daily CBD supplementation (150 mg day-1) improved performance in a 10-min performance-trial on a cycle ergometer. In a randomized, double-blind and placebo-controlled study, 22 healthy participants (n = 11 male and n = 11 female) completed two 10-min performance trials on a WattBike cycle ergometer interspersed with a 3-week supplementation period. Supplementation involved either 150 mg day-1 oral CBD or 150 mg day-1 of a visually identical placebo (PLA). During trials, ratings of perceived exertion (RPE [6-20]), heart rate (HR) and blood lactate (BLa) were collected every 2 min. Mean power (W) was also taken throughout the exercise at each time point. All data were analyzed using two-way ANOVAs. There were no significant differences (P > 0.05) between CBD or PLA groups for mean power (W) during the 10-min performance trial. There were also no significant differences (P > 0.05) in any of the physiological or perceptual parameters (HR, BLa and RPE) between conditions. Three weeks supplementation of a broad-spectrum CBD supplement did not improve performance via any change in RPE during a 10-min time trial on a cycle ergometer, and as such, this evidence does not support the claim that broad-spectrum CBD supplements could be performance-enhancing in this exercise modality.

Exploring the multiple effects of nifedipine and captopril administration in spontaneously hypertensive rats through pharmacokinetic-pharmacodynamic analyses.

This study assessed the pharmacokinetics (PKs) and pharmacodynamics (PDs) of two antihypertensive drugs, nifedipine and captopril, by exploring their main (blood pressure [BP]) and secondary effects (heart rate [HR] and QT interval [QT]) in spontaneously hypertensive rats. This study aimed to assess the relationship between PKs and PDs. Using these PD parameters, BP, HR, and QT during coadministration were estimated. The coadministration of nifedipine and captopril resulted in an increase in nifedipine's total body clearance (CLtot) and a reduction in its mean residence time (MRT) with an increase in the terminal elimination half-life (t1/2) and volume of distribution at steady state (Vdss) of captopril. However, no significant PK interactions were observed. During monotherapy, BP reduced rapidly following nifedipine infusion. Subsequently, despite the increase in nifedipine plasma concentration, BP recovered, likely because of homeostasis. Similar results were observed with coadministration. Subsequently, BP demonstrated a sustained reduction that was greater than or equal to the additive effect estimated from each PK. Captopril exhibited a minimal effect on HR, except for a transient increase observed immediately after starting infusion, consistent with observations during coadministration. Subsequently, the HR reduction was nearly equal to that calculated from the nifedipine PK. QT prolongation was more rapid with captopril than with nifedipine. Although QT prolongation during the initial 60 min of coadministration was approximately the sum of both effects, the recovery period to baseline QT was faster than that in the simulation.

Acute, dose-response effects of guayusa leaf extract on mood, cognitive and motor-cognitive performance, and blood pressure, heart rate, and ventricular repolarization.

PURPOSE: We conducted a randomized, double-blind, placebo-controlled crossover trial in young adults to examine the dose-dependent (600 mg versus 1200 mg), acute effects of consumption of an Ilex guayusa tea extract (GLE) on mood, cognitive and motor-cognitive performance, as well as its acute cardiovascular effects. METHODS: Twenty-five adults (mean ± SD, age = 28 ± 7 y; 9 M/16 F) completed familiarization and then three randomly ordered experimental visits where they consumed either 600 mg (GLE600) or 1200 mg (GLE1200) GLE or placebo (PLA). Following supplement consumption, participants completed a mood state survey, assessments of perceived jitteriness, energy, and focus, and neurocognitive and motor-cognitive testing. Blood pressure (BP), heart rate, and QT interval length were determined before and after supplementation. RESULTS: GLE600 significantly improved total mood disturbance (mean ± SE difference = -6.9 ± 2.6 au, p = 0.034), fatigue-inertia (-2.84 ± 0.89 au, p = 0.008), perceived energy (+13.00 ± 4.49 au; p = 0.02), motor speed (+4.52 ± 1.42 au, p = 0.008), and psychomotor speed (+7.20 ± 2.16 au, p = 0.005) relative to PLA. GLE1200 also improved psychomotor speed (+5.08 ± 2.16 ms, p = 0.045) and uniquely increased motor-cognitive performance as reflected by a decrease in reaction time (-0.106 ± 0.04 ms, p = 0.026) during a neurocognitive hop test. The effect of GLE on jitteriness was both dose- and sex-dependent. Jitteriness increased with increasing GLE dose in women only (p < 0.001). Both GLE600 and GLE1200 similarly increased systolic and diastolic BP by 4-5 mmHg (p ≤ 0.022). Neither GLE600 nor GLE1200 acutely influenced QTc length (p = 0.31). CONCLUSIONS: The goal of GLE supplementation should be considered when selecting a dosing strategy. Lower dosages of GLE (e.g. 600 mg) appear to optimize cognitive and mood-related outcomes while limiting side-effects such as jitteriness in women, and higher dosages may be necessary (e.g. 1200 mg) to promote improvements in motor-cognitive performance.

Antiarrhythmic drug therapy and catheter ablation in patients with paroxysmal or persistent atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Catheter ablation and antiarrhythmic drug therapy are utilized for rhythm control in atrial fibrillation (AF), but their comparative effectiveness, especially with contemporary treatment modalities, remains undefined. We conducted a systematic review and meta-analysis contrasting current ablation techniques against antiarrhythmic medications for AF. METHODS: We searched PubMed, SCOPUS, Cochrane CENTRAL, and Web of Science until November 2023 for randomized trials comparing AF catheter ablation with antiarrhythmics, against antiarrhythmic drug therapy alone, reporting outcomes for > 6 months. Four investigators extracted data and appraised risk of bias (ROB) with ROB 2 tool. Meta-analyses estimated pooled efficacy and safety outcomes using R software. RESULTS: Twelve trials (n = 3977) met the inclusion criteria. Catheter ablation was associated with lower AF recurrence (relative risk (RR) = 0.44, 95%CI (0.33, 0.59), P ˂ 0.0001) and hospitalizations (RR = 0.44, 95%CI (0.23, 0.82), P = 0.009) than antiarrhythmic medications. Catheter ablation also improved the physical quality of life component score (assessed by a 36-item Short Form survey) by 7.61 points (95%CI -0.70-15.92, P = 0.07); but, due to high heterogeneity, it was not statistically significant. Ablation was significantly associated with higher procedural-related complications [RR = 15.70, 95%CI (4.53, 54.38), P < 0.0001] and cardiac tamponade [RR = 9.22, 95%CI (2.16, 39.40), P = 0.0027]. All-cause mortality was similar between the two groups. CONCLUSIONS: For symptomatic AF, upfront catheter ablation reduces arrhythmia and hospitalizations better than continued medical therapy alone, albeit with moderately more adverse events. Careful patient selection and risk-benefit assessment are warranted regarding the timing of ablation.

Retrospective Evaluation of the Effects of Local Anesthesia Before Tooth Extraction Procedures under General Anesthesia on Physiologic Parameters and Postoperative Bleeding in Children.

BACKGROUND: Studies have been conducted to evaluate changes in hemodynamics, postoperative bleeding, and pain in pediatric dental patients receiving general anesthesia (GA). However, a limited number of studies have evaluated the effects of local anesthetics (LA) on tooth extraction procedures during GA. There is no consensus in the literature regarding LA application in the perioperative period for dental treatments performed within the scope of GA. AIM: This study aimed to determine the retrospective physiologic effects of fluctuations in vital signs and postoperative bleeding in children who did or did not receive LA for tooth extraction under GA. METHODS: A retrospective evaluation of 77 patients aged 5.16 ± 1.85 years who had the extraction of primary posterior teeth with or without LA under GA were reviewed in the post-anaesthesia care unit (PACU) for postoperative bleeding and the effects of intraoperative LA on fluctuations in postoperative parameters such as mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (SpO2), respiratory rate (RR), and the end-tidal carbon dioxide (EtCO2). These were compiled from the patient records of the procedures. RESULTS: Significant differences between the baseline and peak MAP (P < 0.001), HR (P = 0.011), and EtCO2 (P = 0.002) were noted in children without LA compared to those who had LA. In addition, substantial variations were observed between the baseline and peak values for MAP (P < 0.001) and HR (P = 0.037) in children who had tooth extraction in the mandibular region. Statistically significant differences were noted between the baseline and peak values for patients who did not receive LA before the extraction of the first primary molar in terms of MAP (P < 0.02) and EtCO2 (P = 0.032). Similarly, significant differences in MAP (P < 0.02) and EtCO2 (P = 0.034) were noted in the extraction of the second primary molar. In addition, there was a significant difference in bleeding based on the number of tooth extractions in those who did not receive LA (P = 0.020). CONCLUSION: This study showed that in children who underwent tooth extraction under GA, additional LA application minimized changes in HR, MAP, and EtCO2, whereas a lack of LA application produced significant fluctuations from baseline to peak values of HR, MAP, and EtCO2. In addition, LA application reduced postoperative bleeding.

The heart rate response to the 6-min walk test in atrial fibrillation patients with or without beta-blockers: Referring to patients with sinus rhythm.

BACKGROUND: The aim was to evaluate the effect of beta-blockers (BB) on the response of heart rate (HR) to 6-min walk test (6MWT) in atrial fibrillation (AF) and whether the AF patients treated with BB have a similar HR response to 6MWT as the AF and sinus rhythm (SR) patients without BB treatment at the same resting HR level. METHODS: The before-after study involving 74 AF patients was to evaluate the effect of BB treatment (pre-BB and with BB). The comparison study included 74 BB-treated AF patients (with BB), 74 matched AF patients without BB (no BB), and 74 SR patients. The percentage increase amplitude of HR (HR-PIA) in 6MWT was calculated: [(the exercise HR - the resting HR)/(the resting HR)] × 100%. RESULTS: The before-after study showed that BB treatment decreased the resting and mean exercise HR (98.6 ± 15.2 vs. 85.5 ± 11.2 bpm and 121.3 ± 17.3 vs. 109.0 ± 16.7 bpm) during 6MWT. The comparison study demonstrated that against the SR, the AF with BB and no BB groups have higher mean exercise HR-PIA (28.2 ± 17.1% and 22.0 ± 9.6%, vs. 6.9 ± 3.7%) when their resting HR is similar. Moreover, the mean exercise HR-PIA was also significantly higher in the with BB group than in the no BB group. CONCLUSION: In AF patients with relatively higher resting HR, BB treatment could decrease the resting and exercise HR during 6MWT. However, BB treatment could not effectively attenuate the exercise HR rise as compared with AF without BB treatment, even with similar resting HR levels.

Total intravenous anesthesia with Ketofol in rabbits: a comparison of the effects of constant rate infusion of midazolam, fentanyl or dexmedetomidine.

BACKGROUND: When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg- 1 minute- 1 [0.3 mg kg- 1 minute- 1 of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min. RESULTS: Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg- 1 and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression. CONCLUSIONS: At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used.

The EC50 of propofol with different doses of dexmedetomidine during gastrointestinal endoscopy: A double-blind, placebo-controlled trial.

PURPOSE: The goal of this study was to evaluate the dose-response relationship between dexmedetomidine and propofol in sedating patients and to determine the optimal dosage of dexmedetomidine during gastrointestinal endoscopy. METHODS: One hundred fifty patients were divided into 5 groups, each receiving a loading dose of dexmedetomidine (0.4, 0.6, 0.8, 1.0 µg/kg) or saline, with propofol for sedation. The median effective concentration (EC50) of propofol was calculated using the modified Dixon up-and-down approach. Adverse effects, vital signs, procedure, and recovery times were recorded. RESULTS: The EC50 of propofol in groups NS, D0.4, D0.6, D0.8, and D1.0 were 3.02, 2.44, 1.97, 1.85, and 1.83 µg/mL, respectively. Heart rate in the dexmedetomidine groups decreased more than the NS group (P < .001). The mean arterial pressure (MAP) in the NS group experienced a decline compared to groups D0.8 and D1.0 when the plasma concentration and effect-site concentration reached equilibrium. Additionally, the respiratory rate was found to be lower in groups NS, D0.4, D0.6, and D0.8 (P < .05). Recovery time in groups D0.8 and D1.0 was longer than the NS group (P < .05). Bruggemann comfort scales score was higher in group D1.0 (P < .05). No significant difference was found in the incidences of hypotension and bradycardia, and the dose of ephedrine and atropine. Respiratory depression was significantly reduced in groups D0.8 and D1.0 compared to the NS group. CONCLUSION: A single dose of 0.6 to 0.8 µg/kg of dexmedetomidine should be recommended in combination with propofol for gastrointestinal endoscopy. And the EC50 of propofol is 1.97 to 1.85 µg/mL.

Dexmedetomidine as a Short-Use Analgesia for the Immature Nervous System.

Pain management in neonates continues to be a challenge. Diverse therapies are available that cause loss of pain sensitivity. However, because of side effects, the search for better options remains open. Dexmedetomidine is a promising drug; it has shown high efficacy with a good safety profile in sedation and analgesia in the immature nervous system. Though dexmedetomidine is already in use for pain control in neonates (including premature neonates) and infants as an adjunct to other anesthetics, the question remains whether it affects the neuronal activity patterning that is critical for development of the immature nervous system. In this study, using the neonatal rat as a model, the pharmacodynamic effects of dexmedetomidine on the nervous and cardiorespiratory systems were studied. Our results showed that dexmedetomidine has pronounced analgesic effects in the neonatal rat pups, and also weakly modified both the immature network patterns of cortical and hippocampal activity and the physiology of sleep cycles. Though the respiration and heart rates were slightly reduced after dexmedetomidine administration, it might be considered as the preferential independent short-term therapy for pain management in the immature and developing brain.

Effects of Acute Guarana (Paullinia cupana) Ingestion on Mental Performance and Vagal Modulation Compared to a Low Dose of Caffeine.

Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared to a low dose of caffeine (CAF) on cognitive and mood parameters, twenty participants completed a double-blind, crossover experiment where they ingested capsules containing the following: (1) 100 mg CAF, (2) 500 mg GUA containing 130 mg caffeine, or (3) placebo (PLA). Cognitive tests (Simon and 2N-Back Task) were performed at the baseline (pre-ingestion) and 60 min after ingestion. The response time for the cognitive tests and heart rate variability were unaffected (p > 0.05) by treatment, although 2N-Back was overall faster (p = 0.001) across time. The accuracy in the 2N-Back Task showed a significant interaction effect (p = 0.029) due to higher post-ingestion versus pre-ingestion levels (p = 0.033), but only with the PLA. The supplements also had no effect on cognitive measures following physical fatigue (n = 11). There was an interaction effect on perceived mental energy, where the pre-ingestion of GUA had lower mental pep ratings compared to post-ingestion (p = 0.006) and post-exercise (p = 0.018) levels. Neither the acute ingestion of GUA nor low dose of CAF influenced cognitive performance or provided consistent benefit on mood or mental workload through vagal modulation. Additional investigations are beneficial to determining the lowest effective dose for CAF or GUA to influence mood and/or cognitive performance.

Cardiorespiratory effects of intramuscular alfaxalone combined with low-dose medetomidine and butorphanol in dogs anesthetized with sevoflurane.

Background: The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied. Aim: To assess the cardiorespiratory function following the IM co-administration of 5 µg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane. Methods: Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A p < 0.05 was considered statistically significant. Results: The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m2 : p < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm5/m2 : p = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide. Conclusion: The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended.