Disparities in Remote Learning Faced by First-Generation and Underrepresented Minority Students during COVID-19: Insights and Opportunities from a Remote Research Experience.

The COVID-19 pandemic forced an unprecedented shift to remote instruction across higher education, reducing access to critically important undergraduate research experience and potentially magnifying inequities faced by first-generation and underrepresented minority (URM) students in higher education. Through a novel course-based undergraduate research experience (CURE) at UCLA, delivered completely online, results of a unique, student-generated survey showed that the transition to remote learning was challenging for all students, increasing student workload, decreasing ability to focus on school, and limiting their ability to succeed. However, results showed significant disparities in remote learning that disproportionately impacted URM and first-generation students. These students had significantly greater expectations to help siblings with remote learning,; URM and first-generation students also suffered greater economic and food insecurity related to COVID-19. At the same time, this study demonstrates how student voices in survey development provide novel and actionable insights. While access to CUREs is often limited by laboratory space, by focusing on the research process, rather than specific laboratory skills, this study provides a scalable pedagogical model for remote undergraduate research experiences. Importantly, this model fostered student engagement and increased interest in further undergraduate research, including topics not directly related to the subject of this study, suggesting that online CUREs can be effective and impactful.

Propranolol increases the complexity of heart rate fluctuations--a mode of antiarrhythmic action?

OBJECTIVE: To study the beta-blocking effect of propranolol on heart rate and arterial blood pressure fluctuations in healthy subjects using linear methods and a set of nonlinear models. METHODS: In a randomized, double-blind, placebo-controlled study, healthy young adults received a 40 mg oral dose of propranolol (n = 12) or placebo (n = 12). The effects of propranolol and placebo were assessed using time series of the RR interval (RRI) and systolic arterial blood pressure (SAP) obtained from continuous ECG and blood pressure signal recordings. Heart rate and systolic arterial blood pressure fluctuations were analyzed using nonlinear and linear methods of time series statistics. RESULTS: Propranolol significantly increased the complexity of heart rate fluctuations in terms of symbol dynamic (SymDyn) entropy and symbol dynamic percentage of forbidden words. Propranolol augmented cross entropy between RRI and SAP and increased fractal dimension of RRI. beta-blockade also affected linear measures of RRI fluctuations by increasing parasympathetic, respiration-related high-frequency (HF) variability and arterial baroreflex-related low-frequency (LF) variability. Propranolol administration, however, had no effect on the complexity of SAP fluctuations assessed using nonlinear time series statistics. CONCLUSIONS: beta-blockade by propranolol has a differential effect on RRI and SAP fluctuations in healthy subjects. Propranolol increases the complexity of RRI fluctuations. The effect is associated with the cardiac vagotonic drug action of propranolol. SAP fluctuations are almost unchanged. The increased complexity of RRI fluctuations may be a beneficial feature of beta-blockade, since many cardiovascular diseases decrease the complexity of RRI time series by dampening cardiovascular reflex actions.

Effects of atipamezole--a selective alpha-adrenoceptor antagonist--on cardiac parasympathetic regulation in human subjects.

1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects of alpha2-adrenoceptor antagonism on cardiac parasympathetic regulation. 2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml(-1) at 50-min intervals. 3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15-0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity. 4 At the end of the three steps of the infusion, the mean (+/-SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml(-1). 5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart. 6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation.

Cardiovascular effects of ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel.

The objective of this randomized, double-masked, cross-over study was to compare the cardiovascular effects of two glaucoma formulations, ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel. Twenty-four young healthy subjects received for 2 weeks either twice daily 0.5% timolol solution or once daily 0.1% timolol hydrogel. Heart rate (HR), blood pressure, atrio-ventricular conduction (PR interval), corrected QT time (QTc) and heart rate variability (HRV) were measured in supine position and during head-up tilted position. The mean peak concentrations of timolol in plasma were significantly higher after administration of 0.5% aqueous solution than after 0.1% hydrogel. A 0.5% timolol aqueous solution decreased HR on average by 3 bpm in supine position and by 7 bpm in head-up tilted position while no significant effects were observed with 0.1% timolol hydrogel. During tilt test HR was significantly lower after administration of timolol aqueous solution than after timolol hydrogel (mean +/- SD, 77 +/- 11 bpm versus 86 +/- 13 bpm, P < 0.05). Timolol aqueous solution slightly decreased QTc during tilt (5.9 +/- 5.6 ms, P < 0.01). During tilt tests, timolol aqueous solution slightly increased atrio-ventricular conduction (7.2 ms, P = 0.02). No significant differences were found in HRV. These results indicate that in healthy volunteers, ophthalmic 0.5% timolol aqueous solution produces more pronounced cardiac beta-blocking effects than 0.1% timolol hydrogel.

Spontaneous baroreflex sensitivity as a dynamic measure of cardiac anticholinergic drug effect.

1. In this study, the analysis of spontaneous baroreflex sensitivity (BRS) was applied to the dynamic assessment of cardiac anticholinergic drug effect in healthy male volunteers. 2. The anticholinergic effects of single intravenous (i.v.) injections of atropine (10 microg kg(-1)), glycopyrrolate (5 microg kg(-1)) and scopolamine (5 microg kg(-1)), as well as a 2-h infusion of glycopyrrolate (5 microg kg(-1) h(-1)) were investigated. Baroreflex sensitivity, a validated measure of cardiac parasympathetic reflex regulation, was repeatedly measured from 5-min recordings of electrocardiogram (ECG) and continuous blood pressure by using the sequence technique, a method based on detection of spontaneous fluctuations in blood pressure and heart rate. 3. Single injections of atropine, glycopyrrolate and scopolamine decreased the mean BRS by 71 +/- 32, 68 +/- 23 and 27 +/- 45%, respectively, whereas the slow glycopyrrolate infusion gradually decreased BRS (up to 83 +/- 11% reduction) and increased both systolic (SAP) and diastolic arterial pressures (DAP) (on an average, by 9 mmHg). 4. During the withdrawal of the parasympathetic blockade (indicated by increasing BRS), the proportion of baroreflex sequences in the recordings increased transiently from 10 up to 20-25%, probably reflecting the restoration of the baroreflex integrity and the baroreflex-induced attempt to counteract the blood pressure increase. 5. The sequence method to study BRS seems to be feasible in the assessment of cardiac anticholinergic drug effects, and it also provides good time resolution for the dynamic measurements.

Effects of tocolytic treatment with ritodrine on cardiovascular autonomic regulation.

OBJECTIVE: To study the acute effects of tocolytic treatment with intravenous ritodrine on cardiovascular autonomic regulation. DESIGN: Validated methods to assess cardiovascular autonomic nervous function-heart rate and blood pressure variability and vagal cardiac baroreflex sensitivity-were measured before and during ritodrine infusion. SETTING: Turku University Central Hospital, Turku, Finland. SAMPLE: Twelve pregnant women admitted to hospital for threatened preterm labour. METHODS: Electrocardiogram and continuous noninvasive finger blood pressure signals were recorded in each woman, resting in a supine position. Autoregressive spectrum analysis was used to quantify short term heart rate and blood pressure variability. Vagal cardiac baroreflex sensitivity was measured as the bradycardia response to an intravenous bolus injection of phenylephrine. MAIN OUTCOME MEASURES: Vagal cardiac baroreflex sensitivity and spectrum analysis indices of short term heart rate and blood pressure variability. RESULTS: Ritodrine significantly decreased vagal cardiac baroreflex sensitivity as well as total (0.00-0.40 Hz), low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) power bands of the heart rate variability spectrum. Ritodrine significantly increased mean heart rate and the low frequency power band of the systolic blood pressure variability spectrum. CONCLUSIONS: In pregnant women with threatened preterm labour intravenous administration of ritodrine decreases vagal cardiac baroreflex sensitivity and vagal modulation of heart rate, and increases sympathetically mediated blood pressure variability. Decreased baroreflex sensitivity and heart rate variability are known to be associated with a poor prognosis in some patient groups, so the effects of ritodrine tocolysis may be unfavourable in women with impaired circulatory homeostasis.

Systemic bioavailability of ocularly applied 1% atropine eyedrops.

PURPOSE: To investigate the pharmacological basis of systemic effects of atropine eyedrops, we estimated the bioavailability of ophthalmic 1% atropine solution in healthy volunteers. METHODS: In a randomized crossover study we administered 0.3 mg atropine either intravenously or ocularly to six healthy volunteers. The plasma concentrations of the biologically active atropine enantiomer, 1-hyoscyamine, were determined using a muscarinic cholinoceptor binding assay. RESULTS: The mean area under the curve from zero to infinitum (AUC0-infinity) for 1-hyoscyamine was 1.862+/-0.580 microg/L x hr after intravenous, and 1.092+/-0.381 microl/L x hr after ocular administration (mean+/-sd, n=6), respectively. The mean bioavailability was 63.5+/-28.6% (mean+/-SD, n=6; min 19%, max 95%). Large interindividual differences characterized the absorption and elimination phases of 1-hyoscyamine kinetics. The terminal half-life (t1/2beta) of 1-hyoscyamine in plasma was not affected by the route of drug administration. CONCLUSION: The systemic bioavailability of 1-hyoscyamine was considerable and may explain the systemic anticholinergic side effects reported in association with the clinical use of atropine eyedrops.

Spectral analysis of heart rate variability as a quantitative measure of parasympatholytic effect--integrated pharmacokinetics and pharmacodynamics of three anticholinergic drugs.

The time course and concentration-effect relationship of parasympatholytic effects of three anticholinergic drugs were investigated using spectral analysis of heart rate (HR) variability. Single intravenous (i.v.) doses of atropine (10 microg/kg), glycopyrrolate (5 microg/kg), scopolamine (5 microg/kg), and placebo were given to eight healthy volunteers in a double-blind, randomized cross-over study. Electrocardiogram (ECG) was recorded at baseline and 2.5, 5, 10, 20, and 30 minutes, and 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration, while the subjects breathed at a fixed 0.25 Hz frequency. The powers of two frequency bands (low frequency [LF] = 0.07-0.15 Hz and high frequency [HF] = 0.15-0.40 Hz) were calculated using stationary time series of R-R intervals (RRI) free from ectopic beats. To perform pharmacokinetic-pharmacodynamic (PK-PD) modeling, venous plasma drug concentrations were measured. Atropine and glycopyrrolate, and, to a lesser extent, scopolamine induced decreases in HF power and increases in LF/HF ratio of HR variability, indicating parasympatholytic activity and corresponding changes in sympathovagal balance. Maximal average decreases in HF power were 99%, 94%, and 82%, respectively, but in two scopolamine subjects, a parasympathomimetic effect was dominant. Interindividual variability was least for the Hayano index of HF power (square root (RRI HF-power)/RRI*100), and profound and consistent decreases were seen after atropine and glycopyrrolate. Pharmacokinetics were best fitted to a two-compartment open model, and effect compartment link modeling using the Hayano index was performed with the atropine and glycopyrrolate data. The best description of the PK-PD relationship for both drugs was achieved using the sigmoidal Emax model. Mean (+/-SD) EC50, sigmoidicity factor (gamma), and equilibration rate constant (k(e0)) estimates were 1.35 (+/-0.27) ng/mL, 6.07 (+/-1.98) and 11.0 (+/-5.28) l/h for atropine and 1.35 (+/-0.49) ng/mL, 4.34 (+/-1.55) and 2.26 (+/-0.81) l/h for glycopyrrolate. Spectral analysis of HR variability appears to be a powerful tool in monitoring parasympatholytic drug activity. A sigmoidal Emax model with an extremely steep concentration-response relationship was revealed for atropine and glycopyrrolate. The effects of scopolamine were more incongruous.

Aqueous humour concentration and the intraocular pressure-lowering effect of topical betaxolol before cataract surgery.

OBJECTIVE: The aim was to study the relationship between aqueous humour betaxolol concentration and intraocular pressure (IOP). METHODS: In this double-blind, randomized study, we administered betaxolol (a) or placebo (b) ocularly to 131 patients scheduled for cataract surgery. The patients were randomly divided into ten groups. In groups 1a and 1b, the drug was scheduled to be instilled 1-2 h, in groups 2a and 2b 12 h, in groups 3a and 3b 24 h, and in groups 4a and 4b 48 h before surgery. The pupil was dilated in all eyes prior to surgery. The IOP was measured with Perkins' applanation tonometer before the instillation of the drug and just before the peribulbar block. Twenty microlitres of 0.5% betaxolol or placebo solution was instilled into the eye. IOP was also measured before instillation of the drug and after 1 2 h in undilated eyes of 20 patients, whose contralateral eye was to be operated on, to rule out the effect of pupil dilation on IOP (groups 5a and 5b). Aqueous humour betaxolol concentrations were analysed using a radioreceptor assay. RESULTS: Betaxolol did not decrease IOP significantly in eyes with pupillary dilation. Both betaxolol and placebo decreased IOP significantly in patients without pupillary dilation, the effect of betaxolol being slightly more pronounced. The betaxolol concentration in aqueous humour was 731 ng m-1 in group la, 2.4 h after drug instillation. Measurable concentrations of betaxolol were also detected in aqueous humour in group 4a 47.7 h after drug administration. CONCLUSION: No correlation between aqueous humour concentration of betaxolol and the effect on IOP was found in eyes where the pupil was dilated before surgery. A single betaxolol dose did not decrease IOP significantly in patients undergoing cataract surgery, but the IOP decreasing effect was, however, clearly seen in patients who did not receive mydriatic drugs. The routine use of topical betaxolol prior to cataract surgery to decrease IOP is not recommended.

Pharmacokinetics and oral bioavailability of glycopyrrolate in children.

Based on plasma levels determined with a radioreceptor assay and following a single oral (50 micrograms/kg) and intravenous (5 micrograms/kg) administration of glycopyrrolate in six healthy children operated twice during a several weeks period, a negligible and variable oral bioavailability was found (3.3; 1.3-13.3%) (median;range). No significant changes in heart rate after oral or intravenous administration of the drug could be seen. Oral glycopyrrolate appears to have no place in paediatric premedication.

Altered cardiovascular autonomic regulation after salmeterol treatment in asthmatic children.

The effects of therapeutic 4 weeks' inhaled salmeterol treatment on the cardiovascular and respiratory autonomic nervous regulation was studied in 11 asthmatic children using inhaled corticosteroid medication. The study followed a randomized, double-blind, placebo-controlled cross-over design. The salmeterol dose was 50 micrograms twice daily. The 4-week salmeterol treatment increased baseline heart rate, low-frequency/high-frequency (LF/HF) variability ratio of R-R intervals, LF variability of systolic arterial pressure (SAP) and maximum tidal volume during the deep breathing test, as well as morning and evening peak expiratory flow (PEF) values. The 4-week salmeterol treatment decreased baseline HF variability of R-R intervals. As a response to the acute 600 micrograms of salbutamol, the changes in heart rate, HF variability of R-R intervals and diastolic blood pressure were significantly smaller after 4 weeks' salmeterol treatment. In conclusion, 4 weeks' therapeutic salmeterol treatment decreases basal cardiovagal reactivity, increases sympathetic dominance in the cardiovascular autonomic balance and improves pulmonary function. A tolerance develops in the cardiovascular response but not in the bronchodilatory response.

Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril.

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

Pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine. A comparison of two injection sites.

BACKGROUND: Intramuscular scopolamine plus morphine premedication is traditionally used when prominent sedative or antisialogogue effect is needed. Knowledge of the pharmacokinetics of scopolamine is limited due to low plasma concentrations found after therapeutic doses. This investigation compares the pharmacokinetics and the clinical responses of this drug combination injected into two commonly used injection sites. METHODS: Twelve ASA class 1 patients scheduled for minor surgery under spinal anaesthesia received scopolamine 6 micrograms/kg plus morphine 200 micrograms/kg injected in either deltoid (group D, n = 6) or gluteal (group G, n = 6) muscle. RESULTS: The peak plasma concentrations of scopolamine after deltoid or gluteal injection (2.2 vs 1.6 micrograms/l) and the time they were reached (17 vs 19 min) were comparable. The absorption of morphine was similar in both groups (Tmax 16 min), but the peak plasma concentrations were higher after deltoid injection (71 vs 49 micrograms/l). The individual variation in the elimination half-lives of both scopolamine and morphine was smaller after deltoid injection (T1/2 scopolamine 1.9 +/- 0.7 vs 2.1 +/- 1.1 h, morphine 1.3 +/- 0.7 vs 2.3 +/- 1.5 h). Moderate slowing (25%) of heart rate was found in both groups. A heavy sedation and antisialogogue effect (VAS) was found in both groups with faster occurrence of maximal effect in group D (60 vs 120-180 min). CONCLUSION: More predictable pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine premedication can be achieved after an injection into deltoid muscle.

Systemic and ocular absorption and antagonist activity of topically applied cyclopentolate in man.

Ocular and systemic absorption and antagonist activity of topical 1% cyclopentolate were studied in 11 elderly patients undergoing extracapsular cataract extraction, and in 8 healthy female volunteers. The patients received two 35 microl drops of cyclopentolate unilaterally and the healthy volunteers one 30 microl drop bilaterally to the lower conjunctival cul-de-sac of the eye. The drug concentrations were measured with radioreceptor assay and receptor occupancies with radiooccupancy assay using isolated rat brain muscarinic cholinoceptors. In the patient group, cyclopentolate concentrations in aqueous humour were approximately 3000 times higher than those in plasma. Muscarinic cholinoceptors were occupied totally (more than 99.9%) by aqueous humour and 3-18% by plasma taken at 55-125 min. after the drug application. In healthy volunteers peak plasma concentration of cyclopentolate, 2.06+/-0.86 (mean+/-S.D.) nM, occurred at 53 min., maximum receptor occupancy being 5.9+/-2.1%. The maximum pupillary dilatation occured at 30 min. after the drug application. At the same time the near point of vision was extended to more than 50 cm in all subjects. After topical application plasma receptor occupancy was not high enough to cause any significant changes in heart rate and in PQ time. None of the subjects experienced subjectively or objectively adverse effects to be attributed to cyclopentolate.

Low-dose transdermal scopolamine decreases blood pressure in mild essential hypertension.

BACKGROUND: Increasing cardiovascular parasympathetic nervous activity could have antihypertensive effects. Low-dose transdermal scopolamine increases vagal-cardiac modulation of sinus node and baroreflex sensitivity in healthy subjects and in cardiac patients. OBJECTIVE: To study the short-term effects of transdermal scopolamine on blood pressure and cardiovascular autonomic control in patients with mild essential hypertension. DESIGN: A randomized, double-blind, placebo-controlled crossover trial with 12 untreated middle-aged [aged 39+/-5 years (mean+/-SD)] patients with mild essential hypertension. METHODS: We recorded the electrocardiogram, auscultatory sphygmomanometric and continuous photoplethysmographic finger arterial pressure, and spirometry signals with patients supine and 70 degrees tilted during controlled (0.25 Hz) breathing. Cardiovascular autonomic regulation was analyzed with power spectrum analysis of R-R interval and arterial pressure variability and a spontaneous sequence method for baroreflex sensitivity. In addition, a deep-breathing test was performed to assess maximal breathing-related sinus arrhythmia. RESULTS: Transdermal scopolamine treatment significantly decreased blood pressure both when patients lay supine and when they were in the 70 degrees tilted position. Scopolamine also slowed heart rate and increased baroreflex sensitivity and R-R interval high-frequency variability for both body positionings. In addition, scopolamine accentuated respiratory sinus arrhythmia during deep breathing and blunted the tilt-induced increase in heart rate. Scopolamine did not affect blood pressure variability. CONCLUSIONS: Transdermal scopolamine decreases arterial pressure, increases baroreflex sensitivity and accentuates vagal-cardiac modulation of sinus node in patients with mild hypertension. Our study supports the hypothesis that increasing cardiovascular parasympathetic activity could have antihypertensive effects in essential hypertension.

Valsalva manoeuvre can be used to study baroreflex sensitivity in pregnancy.

OBJECTIVE: The aim of this study was to assess whether baroreflex sensitivity can be measured in a non-invasive manner with the Valsalva manoeuvre in pregnancy. STUDY DESIGN: Baroreflex sensitivity was measured from the reflex response to phenylephrine injection and phase four of the Valsalva manoeuvre in nine pregnant women at 27 (range 24-33) gestational weeks. RESULTS: Both the phenylephrine test and the Valsalva manoeuvre yielded similar estimates of baroreflex sensitivity (9.3 (4.1) ms/mmHg vs. 8.0 (5.2) ms/mmHg, Pearson's correlation coefficient r = 0.81, P < 0.008, linear regression BRSValsalva (ms/mmHg) = 1.03 x BRSPhenylephrine + 1.59). Comparable changes in heart rate and blood pressure were obtained with the phenylephrine test and the Valsalva manoeuvre. CONCLUSION: The physiological challenge caused by the Valsalva manoeuvre can be used to measure baroreflex sensitivity in pregnancy. A possibility to study baroreflex function non-invasively, without pharmacological intervention, benefits future research of blood pressure regulation in pregnancy.

The dose-response effects of terbutaline on the variability, approximate entropy and fractal dimension of heart rate and blood pressure.

AIMS: To study the dose-response effects of intravenous terbutaline on the cardiovascular and respiratory autonomic nervous regulation. METHODS: The study followed a randomized, placebo-controlled crossover design in six healthy adult volunteers. The terbutaline dose ranged from 10 to 30 microg min(-1) We continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions at baseline and during 3 h drug infusion. The periodic variability components of R-R intervals (time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. The regularity of the time series was assessed by approximate entropy (ApEn) and the convolutedness by fractal dimension (FD). RESULTS: Terbutaline dose-dependently decreased total variability of R-R intervals, low frequency (LF) variability of R-R intervals (10 s waves), high frequency (HF) variability of R-R intervals (respiratory variability), total variability of SAP, HF variability of SAP, baroreflex sensitivity, plasma potassium concentration, approximate entropy of R-R interval and of SAP as well as fractal dimension of R-R interval. Terbutaline dose-dependently increased heart rate, LF/HF ratios of R-R intervals and of SAP, LF variability of SAP, minute ventilation and plasma terbutaline concentration. CONCLUSIONS: Terbutaline infusion decreases parasympathetic cardiovascular reactivity, baroreflex sensitivity, dimensionality of heart rate and plasma potassium concentration; it increases sympathetic dominance in cardiovascular autonomic balance, minute ventilation, and the regularity of heart rate and blood pressure time series.

Altered cardiovascular autonomic regulation after 2-week inhaled salbutamol treatment in asthmatic children.

UNLABELLED: We studied the effects of therapeutic 2-week inhaled salbutamol treatment on the cardiovascular and respiratory autonomic nervous regulation in eight children with asthma. In this randomized, double-blind, placebo-controlled crossover study our test subjects inhaled 200 microg salbutamol or placebo thrice daily for 14 days. After the 14-day treatment we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline and the response to a single 600 microg salbutamol inhalation. The periodic variability components of R-R intervals (the time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis. Two-week salbutamol treatment increased baseline low frequency (LF) variability (P < 0.05) and low frequency/high frequency (LF/HF) variability ratio of R-R intervals (P < 0.05) when compared to the placebo treatment. As a response to the single salbutamol inhalation the increase in LF/HF ratio of R-R intervals was smaller after the 2-week salbutamol treatment (P < 0.01). No significant differences were found in the bronchodilatory response after the treatment period. CONCLUSION: Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. Because these effects were evident 18 h after cessation of the therapy they are likely to reflect the adaptation of organ responses to regular therapy or altered central autonomic regulation rather than direct drug effect. A slight tolerance developed in the sympathovagal cardiac response but not in the bronchodilatory response.

The acute effects of inhaled salbutamol on the beat-to-beat variability of heart rate and blood pressure assessed by spectral analysis.

AIMS: We wanted to study the effects of a 600 micrograms inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma. METHODS: In this randomized, double-blind, placebo-controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R-R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross-spectral analysis. RESULTS: Salbutamol significantly decreased the total and low frequency (LF) variability of R-R intervals as well as the high frequency (HF) variability of R-R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R-R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation. CONCLUSIONS: We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.

Effects of low-dose transdermal scopolamine on autonomic cardiovascular control in healthy young subjects.

We studied how posture influences the effects of transdermal scopolamine on autonomic cardiovascular regulation in a randomized, double-blind, placebo-controlled crossover study of 10 healthy young volunteers. We recorded the electrocardiogram and auscultatory sphygmomanometric and continuous non-invasive finger arterial pressure (Finapres device) to obtain signals for the beat-by-beat R-R interval and systolic, mean and diastolic pressures. R-R interval and arterial pressure variabilities were characterized by power spectral analysis. Scopolamine increased the mean R-R intervals and reduced arterial pressure in both the supine and the standing positions, but did not affect blood pressure variability. Scopolamine increased the total variability of R-R interval and its mid- (0.07-0.15 Hz) and high- (0.15-0.40 Hz) frequency band power in the standing position during controlled breathing at 0.25 Hz. In the supine position, scopolamine did not affect R-R interval variability. In the deep breathing test, scopolamine increased the maximal expiratory-inspiratory R-R interval ratio. This study showed that low-dose scopolamine increases vagal cardiac inhibition in both supine and standing positions in healthy volunteers. However, scopolamine increases heart rate variability only in the standing position during partial vagal withdrawal. The study also demonstrates that transdermal scopolamine decreases blood pressure in healthy young subjects.