Acute Increase Research Articles

Is Workload Associated With Oblique Injuries in Professional Baseball Players?

Oblique strains have become a common injury among professional baseball players. The influence of player workload on oblique strains remains unknown. To determine whether workload is a risk factor for oblique strains in professional baseball players. We hypothesized that fewer days of rest, more innings pitched/fielded per game, and more batters faced/plate appearances per game would significantly increase a player's risk of sustaining an oblique strain. Case-control study; Level of evidence, 3. All professional baseball players who sustained an oblique strain between 2011 and 2017 were identified using the Major League Baseball Health and Injury Tracking System. A separate dataset of player usage-days of rest per game, innings pitched or fielded per game, and batters faced or plate appearances per game-was used to determine the workload. We compared these usage variables between player games ≤2, ≤6, ≤12, and >12 weeks before a documented oblique strain with player games from a control group of players with no oblique strains. In a paired analysis, we compared acute (player games ≤2, ≤6, and ≤12 weeks preinjury) versus chronic (player games >12 weeks preinjury) workloads. There were 311 oblique strains in pitchers and 392 oblique strains in position players during the study period. In pitchers, more innings pitched and more batters faced were associated with a subsequent oblique strain (P < .001 for all). In position players, fewer days of rest, more innings fielded, and more plate appearances were associated with a subsequent oblique strain (P < .001 for all). Pitchers who pitched ≥7 innings per game had a 2.4-fold (95% CI, 1.4-4.9) increased risk of subsequent oblique strain compared with those who pitched 1 inning per game. The percentage of position players with a subsequent oblique strain increased by 2.1-fold (95% CI, 1.3-3.5) with >4 plate appearances compared with 1 plate appearance per game. Our analysis demonstrated that workload was associated with an increased risk of sustaining an oblique injury in professional baseball players. High workload over time was more predictive of oblique strains compared to acute increases over chronic baseline workload.

Out of the Closet, but Not Out of the Woods: The Longitudinal Associations Between Identity Disclosure, Discrimination, and Nonsuicidal Self-Injury Among Sexual Minoritized Young Adults.

Sexual minoritized individuals engage in non-suicidal self-injury (NSSI) at higher rates than their heterosexual peers. Disclosing one's sexual minoritized identity can put one at risk for experiencing discrimination, which is linked to greater engagement in NSSI. However, discrimination has yet to be tested as a mechanism linking sexual identity disclosure to NSSI. Understanding how sexual identity disclosure impacts NSSI has the potential to inform interventions to reduce sexual orientation disparities in NSSI. To address this gap, the current study examined sexual orientation-based discrimination as a mediator of the longitudinal association between sexual identity disclosure and NSSI among 792 sexual minoritized young adults. Higher levels of disclosure at baseline were associated with greater likelihood of NSSI at two-month follow-up via greater discrimination at one-month follow-up, even after controlling for baseline levels of depression and demographic characteristics. The indirect effect became non-significant after controlling for previous levels of discrimination and NSSI. Findings provide partial support for the hypothesis that identity disclosure may precede exposure to discrimination and, in turn, engagement in NSSI. However, identity disclosure does not appear to predict acute increases in discrimination. Future research is encouraged to examine these prospective associations with longer intervals between assessments, as the indirect effect of identity disclosure on NSSI via discrimination may continue to accumulate over time. Findings highlight the need to reduce discrimination following sexual identity disclosure through the implementation of equitable and affirmative practices in school, healthcare, and other settings to improve the well-being of sexual minoritized young adults.

Interplay of electrical and mechanical properties in transgenic rabbit models of long-QT and short-QT syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SNF Introduction Long-QT syndrome (LQTS) and short-QT syndrome (SQTS) are cardiac disorders primarily affecting electrical function but secondarily also impacting on mechanical features through electro-mechanical coupling (EMC). This study delves into in vivo and cellular electro-mechanical function and explores the impact of acute mechanical changes on the electrical phenotype, termed mechano-electrical coupling (MEC), in transgenic rabbit models. Aim This study aims to investigate the interrelationship between electrical and mechanical properties in LQTS and SQTS rabbit models, examining how acute mechanical alterations influence the electrical phenotype and exploring cellular electro-mechanical characteristics. Methods We examined 12-lead ECGs in LQT2, wildtype (WT), and SQT1 adult rabbits under various preload and afterload conditions. Additionally, patch-clamp and ionoptix experiments on isolated ventricular cardiomyocytes were conducted to investigate cellular electrical and mechanical characteristics. Results Baseline heart-rate corrected QTc intervals were prolonged in LQT2 (p&amp;lt;0.0001) and shortened in SQT1 (p=0.012) compared to WT. QT-dispersion was solely increased in LQT2 (p&amp;lt;0.05). Acute increase in preload and in afterload prolonged QTc intervals in all groups, while reduced preload shortened QTc intervals. MEC (mechano-induced ΔQTc) varied among genotypes; in LQT2, QTc changes were more significant than in WT (p&amp;lt;0.0001 with increased preload, p&amp;lt;0.001 with decreased preload, and p&amp;lt;0.05 with increased afterload). SQT1 showed a trend towards less pronounced changes compared to WT only after increased preload (p=0.11). At the cellular level, action potential duration was longer in LQT2 (p&amp;lt;0.001) and shorter in SQT1 (p&amp;lt;0.0001) compared to WT. While cardiomyocytes from WT and SQT1 showed similar Ca2+ transient durations at 1Hz, 0.5Hz, and 0.25Hz, in LQT2 cardiomyocytes Ca2+ transients were significantly prolonged at 0.5 (p&amp;lt;0.001) and 0.25Hz (p&amp;lt;0.05) in line with the pronounced APD prolongation. Additionally, LQT2 exhibited significantly more pro-arrhythmic Ca2+ oscillations, which may contribute to arrhythmia formation in LQT2s. Moreover, LQT2 exhibited a slower calcium transient upstroke velocity and a reduced cellular contraction velocity and peak sarcomere shortening at all frequencies, demonstrating a mechanical impairment compared to WT and SQTS cardiomyocytes. Conclusions Acute mechanical alterations induce electrical changes through MEC in LQT2, WT, SQT1 rabbits. The magnitude of these changes correlates with baseline QTc, exhibiting the most prominent effects in LQT2. Consistent findings between cellular electro-mechanical assessments and in vivo measurements underscore the significance of cardiomyocytes in unravelling the mechanisms behind EMC and MEC. This intricate interplay between electro-mechanical properties in cardiac disorders, highlighting the necessity of considering both aspects when investigating arrhythmia mechanisms.

Acute increases in physical activity and temperature are associated with hot flash experience in midlife women.

This study determined the association between acute changes in physical activity, temperature, and humidity and 24-hour subjective and objective hot flash experience. Data collection occurred during the cooler months of the year in Western Massachusetts (October-April). Women aged 45-55 across three menopause stages (n = 270) were instrumented with ambulatory monitors to continuously measure hot flashes, physical activity, temperature, and humidity for 24 hours. Objective hot flashes were assessed via sternal skin conductance, and subjective hot flashes were recorded by pressing an event marker and data logging. Physical activity was measured with wrist-worn accelerometers and used to define sleep and wake periods. Logistic multilevel modeling was used to examine the differences in physical activity, humidity, and temperature in the 10 minutes preceding a hot flash versus control windows when no hot flashes occurred. The odds of hot flashes were considered separately for objective and subjective hot flashes as well as for wake and sleep periods. Data from 188 participants were included in the analyses. There was a significantly greater odds of a hot flash following acute increases in physical activity for objective waking hot flashes (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.17-1.47; P < 0.001) and subjective waking hot flashes (OR, 1.16; 95% CI, 1.0-1.33; P = 0.03). Acute increases in the actigraphy signal were associated with significantly higher odds of having an objective (OR, 1.17; 95% CI, 1.03-1.35; P < 0.01) or subjective (OR, 1.72; 95% CI, 1.52-2.01; P < 0.001) sleeping hot flash. Increases in temperature were significantly related to the odds of subjective sleeping hot flashes only (OR, 1.38; 95% CI, 1.15-1.62; P < 0.001). There was no evidence for a relationship between humidity and odds of experiencing any hot flashes. These results indicate that acute increases in physical activity increase the odds of hot flashes that are objectively measured and subjectively reported during waking and sleeping periods. Temperature increases were only related to subjectively reported nighttime hot flashes.

Acute hemodynamic effects of the Marshall-Plan ablation on left and right atrial pressure: does 'respecting atrial physiology' prevent stiff left atria? A retrospective single- center analysis

Abstract Introduction Stiff left atrium (STILA)-syndrome is a relevant concern after extensive ablation in the left atrium (LA) e.g. in persistent atrial fibrillation (AF). STILA often causes disabling heart failure symptoms worse than the initial arrhythmia symptoms. Therefore preventing adverse ablation-induced hemodynamic effects is of utmost concern. Methods This single-center study retrospectively analyzed data from 89 consecutive patients who underwent biatrial ablation for AF following the Marshall-Plan between February 2022 and November 2023. The procedures included ablation of the CTI and PVI where necessary followed by ablation of a LA roof line and ablation of the lateral mitral isthmus after previously performed ethanol ablation of the vein of Marshall. This lesion set is considered to maintain physiological activation of the LA. This study evaluates acute hemodynamic changes following the Marshall-Plan. Invasive hemodynamic measurements of mean left and right atrial pressure, as well as A- and V-waves were performed in all patients before and after the ablation. We assessed the acute changes of atrial hemodynamics in these procedures. Continuous data are given as mean ± standard deviation, categorical data are expressed as number and percentages. Differences between groups were determined by Student’s t-test, chisquare-test, and Fisher’s exact test using SPSS software. A p-value of &amp;lt;0.05 was deemed significant. Results The patients' mean age was 70.1 ± 7.5 years and 39.0% were female. Mean BMI was 28.9 ± 5.2 kg/m². Procedures were performed under general anesthesia (with a PEEP of 5.5cmH2O (2-10 cmH2O)) and took 181 minutes on average. Left atrial mean pressure averaged at 15.7mmHg before the procedure. The overall average change of left atrial mean pressure was +1,8mmHg. The average change in left atrial A- and V-Wave amounted to -1.9mmHg and -0.9mmHg respectively. The pre-procedural average right atrial mean pressure was 12.1mmHg. Right atrial mean pressure inclined by +1.6mmHg. The average change in right atrial A- and V-Wave was +0.6mmHg and +1.1mmHg respectively. The i.v. administered volume averaged 1900 ± 285ml. 3.3% of patients showed an increase of mean LA-pressure &amp;gt;9mmHg. Those patients tended to be older (74.3years), were all male (100%) and had a higher BMI (31.5 kg/m²) as well as higher amount of i.v. administered volume (2333ml) and a longer procedure (213min). Discussion Complex and extensive biatrial ablation following the Marshall-Plan does not lead to acute significant increases in left or right atrial pressures. The administered i.v. volume might explain the slight increases observed. In our observation, the rate of significant increases in LA-pressure is low. This suggests that disrupting the (left) atrial activation pattern might play a role in the development of diastolic dysfunction and thereby STILA-syndrome. Respecting atrial physiology may be beneficial for preventing adverse hemodyamic changes after ablation.

Preventing vagal response during pulmonary vein isolation with pulsed field ablation: impact of the order of the targeted pulmonary veins

Abstract Background Vagal responses are frequently observed during pulmonary vein isolation (PVI). Radiofrequency ablation of the anterior right ganglionated plexus (ARGP) before PVI has been demonstrated to effectively prevent VR occurrence. Pulsed-field ablation (PFA) has emerged as an alternative energy source for PVI. Despite PFA being selective for the myocardium, intraprocedural VRs and reversible effects on ganglionated plexi (GP) have been documented during PVI. Purpose We aimed to investigate whether initiating PVI from the right superior pulmonary vein (RSPV) before any other pulmonary veins (PVs) could prevent VR occurrence via concomitant transient ARGP modulation. Methods 60 consecutive paroxysmal atrial fibrillation patients undergoing PVI with the pentaspline PFA ablation catheter were prospectively included. In the first 30 patients, PVI was started from the left superior pulmonary vein (LSPV-first group). In the last 30 patients, the RSPV was targeted first, followed by the left PVs, and finally the right inferior PV (RSPV-first group). VR was defined as sinus bradycardia (&amp;lt;40 beats/min), asystole, or atrioventricular block (AVB). Heart rate (HR) was evaluated at baseline, during PVI, and post-ablation to assess GP modulation. Results Baseline characteristics were similar between the two study groups. VR during PVI occurred in 22 (73%) patients in the LSPV-first group and 3 (10%) in the RSPV-first group (Figure1, p&amp;lt;0.001). A higher rate of VRs was observed in patients in the LSPV-first group compared to patients in the RSPV-first group during ablation of the LSPV and LIPV (73% vs. 7%, p&amp;lt;0.001 and 27% vs. 0%, p=0.005, respectively), while no differences were found during ablation of the right PVs. Temporary pacing was employed in 10 (33%) patients in the LSPV-first group and 3 (10%) in the RSPV-first group (p=0.028). RSPV isolation induced similar acute HR increase in the two groups (13±9 bpm vs 13±10 bpm, p=0.9). However, no significant HR variation was documented in both groups at the end of the procedure compared to baseline (all p&amp;gt;0.05). Conclusion PVI with PFA is frequently associated with intraprocedural VRs when ablation is initiated from the LSPV. However, an RSPV-first approach determined transient HR increase and reduced VR occurrence.Figure 1

Accelerated pacing reduces left heart filling pressures: a novel therapy for heart failure with preserved ejection fraction?

Abstract Background The recent MyPACE trial demonstrated significant improvement of quality-of-life, physical activity, and atrial fibrillation (AF) burden with accelerated pacing as compared to the standard 60bpm back-up rate setting in patients with heart failure with preserved ejection fraction (HFpEF) and indication for pacemaker therapy. We hypothesized that a potential working mechanism underlying these improved outcomes lies in the reduction of left heart filling pressures during accelerated pacing, reducing congestion and atrial stretch. Aim To assess the acute effects of accelerated atrial pacing on left heart filling pressures in consecutive AF patients undergoing catheter ablation. Methods Fifty AF patients undergoing catheter ablation were prospectively enrolled for accelerated atrial pacing. As illustrated in Figure 1, pacing was performed proximally in coronary sinus (CS). Pacing rate was increased incrementally from resting heart rate by 10-bpm increments up to Wenckebach rhythm, with 30-sec intervals of pacing on and off for hemodynamic stabilization. Left atrial pressure (LAP) was continuously monitored via a fluid-filled transseptal sheath (SL0 sheath, Abbott). Acute pacing-induced changes in mean LAP and PR-interval were evaluated at each pacing rate and compared between resting heart rate, the patient-specific optimal heart rate (i.e., the rate resulting in the lowest mean LAP), and the maximum pacing rate. Results Atrial pacing acutely decreased mean LAP from 14.8[9.8; 18.4] to 12.8[8.5; 15.8]mmHg (median[IQR], p&amp;lt;0.001) as heart rate increased from 51[47; 61] to 90[70; 100]bpm (p&amp;lt;0.001) (Figure 2, resting versus optimal category). Among the 50 patients included, only 4 did not exhibit a decrease in LAP. Further increasing pacing rate to a maximum of 130[100; 140]bpm resulted in an acute LAP increase to 16.2[12.7; 19.9]mmHg (p&amp;lt;0.001) to values above resting mean LAP. Accelerated pacing induced negative AV dromotropy, i.e., lengthening of the PR-interval from 169[150; 185] to 186[164; 209]ms (p=0.003) and 270[217; 310]ms (p&amp;lt;0.001). Conclusion Our study demonstrated that moderately accelerated atrial pacing reduced mean LAP in AF patients undergoing catheter ablation. While our primary focus was on acute response in AF patients, the reduction in mean LAP during moderate pacing rates may suggest a promising therapeutic approach for managing HFpEF patients. However, caution is warranted as pacing rates beyond the optimal range led to a marked increase in LAP. Additionally, increasing pacing rates were observed to induce varying degrees of AV-node dromotropy, which potentially modulates therapy response.Fig 1. Overview of clinical protocolFig 2. Response to accelerated pacing

Development of chronic thresholds in His bundle pacing: single-center experience over 7 years in 426 patients

Abstract Background Conduction system pacing (CSP), e. g. by His bundle pacing (HBP) has the potential to perform highly synchronized ventricular pacing in patients with AV block and narrow QRS complex or right bundle branch block. Therefore, CSP is recommended in these patients to prevent pacing-induced cardioomyopathy. However, there have been reports about an acute and chronic threshold increase in HBP that may cause asystole in pacemaker-dependent patients. Purpose We checked the development of chronic pacing thresholds, the incidence of dislodgements and of consecutive asystole in patients with HBP. Methods All consecutive patients with HBP attempted in our center between 6/2016 and 11/2023 were enrolled. Pacing and sensing parameters over 36 months together with the follwing events were collected and analyzed: His bundle lead dislodgement, loss of capture, threshold increase to ≥3.0V/1.0 ms, emergency admission due to syncope with loss of HBP and asystole. Results In 426 patients (78±11 years, 38% female, 90% AV block, left ventricular ejection fraction 54±10%), HBP was attempted and in 388 patients successful (47% non-selective, 53% selective HBP), 16 patients were converted to left bundle branch area pacing, 22 implantations attemps were unsuccessful. Pacing and sensing performance during follow-up are listed in the Fig. There were 3 lead dislodgements (2 patients with Twiddler syndrome), 1 loss of capture (patient with sinus node disease), and 13 increases of pacing thresholds to ≥3.0V/1.0 ms, summing up to 17 events over 3 years (4.3%). No patient had a clinical event due to threshold increase or loss of HBP capture. All His bundle threshold increases were clinically silent because patients were not pacemaker-dependent, had non-selective HBP with myocardial capture serving as a "back-up" or due to a previously implanted right ventricular back-up lead. Conclusions There is a modest pacing threshold increase in His bundle thresholds from 1.1 to 1.8V@1.0 ms over a period of 3 years. However, this did not cause clinically relevant events in our patient cohort.Chronic pacing and sensing parameters

Acute haemodynamic changes during left atrial appendage closure

Abstract Purpose Left atrial appendage closure (LAAC) presents an alternative treatment for stroke prevention in atrial fibrillation (AF) in patients with contraindication for long-term anticoagulation. However, even in patients in AF, left atrial appendage plays an important role in reservoir function of left atrium. The purpose of this study was to assess acute hemodynamic effects during LAAC. Methods Consecutive patients indicated for LAAC from January 2022 to October 2023 were enrolled. The invasive hemodynamic measurements were done at the beginning of the procedure after transseptal puncture, and at the end from the procedure after device deployment. Following parameters were measured: systolic, and diastolic blood pressure, and pressure in left atrium (LA), all measurements were done at rest and after 3 minute isometric exercise (handgrip). Results Thirty-two patients were included (age 76,2+7,1 yrs, 22 (69%) males, 23 (72%) permanent AF, left ventricular ejection fraction 52+11,8%). No patients experienced moderate/severe mitral insufficiency, the saline intake during procedure was 738 ml. Isometric exercise significantly increased the LA pressure: the LA pressures (rest/exercise) were 13.7+6.7 mmHg/16.7+8.8 mmHg (p=0.003) at the beginning of the procedure, and 17.0+7.3mmHg/20.0+7.3 mmHg (p=0.005) after device deployment. The LA pressure obtained after device deployment (both rest/exercise) were significantly higher compared to values obtained at the beginning of the procedure. (p=0.003). Conclusions LAAC is associated acute increase of both rest and exercise LA pressure. Whether its acute negative effect remains over time needs further investigation.

Time-dependent activation and repolarization changes following left bundle branch area pacing versus conventional biventricular pacing in patients with dyssynchronous heart failure

Abstract Background Cardiac Resynchronization Therapy (CRT) is the standard treatment for patients with dyssynchronous heart failure. Despite the effectiveness of conventional biventricular pacing (BiVP), 6-16% of patients develop ventricular tachyarrhythmias (VTAs) within a year of implantation. The relationship between BiVP and the development of VTAs is still under debate. During BiVP, the left-sided epicardium-to-endocardium activation creates a non-physiological activation and hence a non-physiological repolarization, which might trigger VTAs. A novel alternative treatment option to BiVP that on the contrary induces a left ventricular endocardium-to-epicardium activation, is left bundle branch area pacing (LBBAP). We hypothesized that LBBAP leads to a more homogenous repolarization than conventional BiVP. Purpose To compare time-dependent activation and repolarization changes in patients with dyssynchronous heart failure receiving LBBAP versus BiVP. Methods Patients eligible for CRT who underwent LBBAP (n=21) or BiVP (n=94) were retrospectively included. Standard 12-lead electrocardiograms obtained prior to implantation [baseline], shortly following implantation (0-2 days, [acute phase]), and after prolonged pacing during follow-up (31-180 days, [chronic phase]) were analyzed. QRS duration and QRS area were calculated through reconstruction of the vectorcardiogram and further analyzed together with corrected QT (QTc) and corrected Tpeak-Tend (Tp-e,c) intervals using a semi-automatic approach in MATLAB. Differences between LBBAP and BiVP patients were determined using the Mann-Whitney U-test. Time-dependent changes within groups were determined using the Wilcoxon signed-rank tests. Significance was defined as a p-value ≤0.05. Results (see figure): Compared to baseline, QRS duration and QRS area decreased significantly during the acute phase (both p &amp;lt; 0.01) and stabilized during chronic pacing for both BiVP and LBBAP patients. Differences in QRS duration or QRS area between LBBAP and BiVP were not significant at any of the time points. In the acute phase, BiVP resulted in a temporary and significant prolongation of both QTc and Tp-e,c compared to baseline (both p &amp;lt; 0.01). However, there was a subsequent shortening observed between the acute and chronic phases for both QTc and Tp-e,c (both p &amp;lt; 0.01). Compared to baseline, LBBAP acutely shortened Tp-e,c (p = 0.02) and tended to shorten QTc. During chronic pacing, LBBAP shortened QTc and Tp-e,c compared to baseline (p = 0.01 and p &amp;lt; 0.01). The decreases in QTc and Tp-e,c were larger in LBBAP than in BiVP patients in the acute and chronic pacing phase (all p &amp;lt;0.01). Conclusion CRT induces activation changes in both BiVP and LBBAP patients to a comparable extent. While BiVP leads to an acute increase in repolarization dispersions, LBBAP reduces markers of repolarization dispersion compared to baseline. The diminished dispersion of repolarization might contribute to an antiarrhythmic effect with LBBAP.

Uninterrupted in vivo cerebral microdialysis measures of the acute neurochemical response to a single or repeated concussion in a rat model combining force and rotation

Altered extracellular amino acid concentrations following concussion or mild traumatic brain injury can result in delayed neuronal damage through overactivation of NMDA glutamatergic receptors. However, the consequences of repeated concussions prior to complete recovery are not well understood. In this study, we utilized in vivo cerebral microdialysis and a weight-drop model to investigate the acute neurochemical response to single and repeated concussions in adult rats that were fully conscious. A microdialysis probe was inserted into the hippocampus and remained in place during impact. Primary outcomes included concentrations of glutamate, GABA, taurine, glycine, glutamine, and serine, while secondary outcomes were righting times and excitotoxic indices. Compared to sham injury, the first concussion resulted in significant increases in glutamate, GABA, taurine, and glycine levels, longer righting times, and higher excitotoxic indices. Following the second concussion, righting times were significantly longer, suggesting cumulative effects of repeated concussion while only partial increases were observed in glutamate and taurine levels. GABA and glycine levels, and excitotoxic indices were comparable to sham injury. These findings suggest that single and repeated concussions may induce acute increases in several amino acids, while repeated concussions could exacerbate neurological symptoms despite less pronounced neurochemical changes.

Evaluation of the Efficacy and Safety of Nicardipine Versus Clevidipine for Blood Pressure Control in Hypertensive Crisis

BackgroundHypertensive crisis is an acute increase in blood pressure >180/120 mm Hg. A titratable antihypertensive agent is preferred to lower blood pressure acutely in a controlled way and prevent an abrupt overcorrection. Nicardipine and clevidipine are both dihydropyridine calcium channel blockers that provide unique benefits for blood pressure control. ObjectiveThe purpose of this study was to compare the efficacy and safety of nicardipine or clevidipine for blood pressure control in the setting of hypertensive crisis. MethodsThis was a single-center, retrospective cohort study. Eligible patients received either nicardipine or clevidipine for the treatment of hypertensive crisis. The primary outcome was achievement of 25% reduction in mean arterial pressure at 1 h. The secondary outcome was achievement of a systolic blood pressure (SBP) of <160 mm Hg at 2–6 h from the start of the infusion. ResultsThis study included a total of 156 patients, 74 in the nicardipine group and 82 in the clevidipine group. The SBP on admission and at the start of the infusion were similar between groups. There was no difference between groups in achieving a 25% reduction in mean arterial pressure at 1 h. Nicardipine achieved an SBP goal of <160 mm Hg at 2–6 h significantly more often than the clevidipine group (89.2% vs. 73.2%; p = 0.011). ConclusionsThere is no difference between agents for initial blood pressure control in the treatment of hypertensive crisis. Nicardipine showed more sustained SBP control, with a lower risk of rebound hypertension and a significant cost savings compared with clevidipine.

Dose-dependent LSD effects on cortical/thalamic and cerebellar activity: brain oxygen level-dependent fMRI study in awake rats.

Lysergic acid diethylamide is a hallucinogen with complex neurobiological and behavioural effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of lysergic acid diethylamide in fully awake, drug-naive rats. We hypothesized that lysergic acid diethylamide would show a dose-dependent increase in activity in the prefrontal cortex and thalamus while decreasing hippocampal activity. Female and male rats were given intraperitoneal injections of vehicle or lysergic acid diethylamide in doses of 10 or 100 µg/kg while fully awake during the imaging session. Changes in blood oxygen level-dependent signal were recorded over a 30-min window. Approximately 45-min post-injection data for resting-state functional connectivity were collected. All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific increases and decreases in global brain activity and changes in functional connectivity. Treatment with lysergic acid diethylamide resulted in a significant dose-dependent increase in negative blood oxygen level-dependent signal. The areas most affected were the primary olfactory system, prefrontal cortex, thalamus and hippocampus. This was observed in both the number of voxels affected in these brains regions and the changes in blood oxygen level-dependent signal over time. However, there was a significant increase in functional connectivity between the thalamus and somatosensory cortex and the cerebellar nuclei and the surrounding brainstem areas. Contrary to our hypothesis, there was an acute dose-dependent increase in negative blood oxygen level-dependent signal that can be interpreted as a decrease in brain activity, a finding that agrees with much of the behavioural data from preclinical studies. The enhanced connectivity between thalamus and sensorimotor cortices is consistent with the human literature looking at lysergic acid diethylamide treatments in healthy human volunteers. The unexpected finding that lysergic acid diethylamide enhances connectivity to the cerebellar nuclei raises an interesting question concerning the role of this brain region in the psychotomimetic effects of hallucinogens.

Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans.

LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester-enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport. We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins. As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; P≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; P=0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins. Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.

MONITORING OF ACUTE TENSION (BLOOD PRESSURE) INCREASES DETECTED IN HOSPITAL EMERGENCIES

Objective: To assess whether, after an acute increase in blood pressure in the hospital emergency department, the control objectives are subsequently achieved in primary care. Design and method: Cross-sectional descriptive study assessing blood pressure figures in the Emergency Department, the days elapsed until the first visit to the Primary Care Center since the incident and until the visit in which minimal control has been obtained (defined as blood pressure &lt;140/90 mmHg). Results: 96 patients were preselected, of which only 85 met the inclusion criteria for the study, 49 women, mean age was 69 years, 72 had a previous diagnosis of Hypertension with a mean of 10 (standard deviation +/- 9) years of evolution, 66 with previous pharmacological treatment, 20 had been referred from Primary Care. The mean systolic blood pressure on arrival at the emergency room was 181 mmHg (standard deviation +/- 20) and at discharge 152 mmHg (standard deviation +/-18.5), the diastolic blood pressure on arrival at the emergency room was 91 mmHg (standard deviation +/- 16) and at discharge 82 mmHg (standard deviation +/-11.7). From the 85 patients included, 84 followed primary care controls (98%) and 60 achieved control of arterial hypertension (70.5%), with a median in days of 12 (interquartile range 3-35) and 90 respectively (interquartile range 26.5-147.5). Conclusions: This study allows us to know that a high percentage of patients consult the Primary Care after an acute increase in blood pressure but interventions could be proposed to further reduce the time of this coordination in some cases. The blood pressure goal was achieved in 70.5% of the patients, so the causes of suboptimal control in the remaining patients would have to be reviewed.

The Contribution of Na+ or Cl− to Central NaCl−induced Cardiovascular Responses in Rodents

A high salt diet elevates plasma and cerebrospinal fluid NaCl concentrations in salt-sensitive hypertensive humans and animals. Acute or chronic intracerebroventricular (ICV) infusion of hypertonic NaCl elevates sympathetic nerve activity and blood pressure. However, it is unclear which ion, Na+ or Cl−, contributes to this response. The purpose of the present study was to investigate the extent to which acute increases in cerebrospinal fluid Na+ and Cl− increase ABP and HR in rodents. Male Sprague Dawley rats (n=6; body weight: 270-350 g) were anesthetized with isoflurane (2-3% in 100% O2) and instrumented with a lateral ventricle cannula for ICV infusions. Additionally, arterial and venous catheters were implanted to record BP and administer drugs, respectively. At least 4 days after recovery, ABP and HR were measured in response to ICV infusion (10uL over 10 min) of the following solutions: artificial cerebrospinal fluid (aCSF); 0.3 M and 0.6 M NaCl; 0.15 M and 0.3 M Na2SO4, and 0.3 M and 0.6 M NH4Cl. Each animal received one ICV infusion of each solution every other day. Data are presented as mean ± SE. Baseline ABP and HR did not differ across each ICV infusion (ABP: from 98 ± 6 mmHg to 106 ± 6 mmHg; and HR: from 337 ± 17 bpm to 363 ± 12 bpm). As expected, ICV infusion of 0.3 M and 0.6 M NaCl produced concentration-dependent increases in ABP (Δpeak ABP 0.3 M NaCl: 17 ± 2 mmHg; 0.6 M NaCl: 26 ± 3 mmHg). While ICV infusions of Na2SO4 at both concentrations also increased ABP, the magnitudes were reduced compared to NaCl (Δpeak ABP 0.15 M Na2SO4: 11 ± 2 mmHg; 0.3 M Na2SO4: 17 ± 3 mmHg). On the other hand, infusion of NH4Cl produced a modest increase in ABP (Δpeak ABP 0.3 M NH4Cl: 8 ± 2 mmHg and 0.6 M NH4Cl: 9 ± 3 mmHg). However, it did not differ from aCSF (Δpeak ABP aCSF: 6 ± 2 mmHg). HR responses induced by NaCl varied greatly (Δpeak HR 0.3 M NaCl: 15 ± 22 bpm; 0.6 M NaCl: 19 ± 17 bpm). In contrast, both concentrations of Na2SO4 consistently increased HR (Δpeak HR 0.15 M Na2SO4: 64±10 bpm; 0.3 M Na2SO4: 60±10 bpm). Additionally, ICV infusions of NH4Cl also tended to enhance HR (Δpeak HR 0.3 M NH4Cl: 38 ± 13 bpm and 0.6 M NH4Cl: 41 ± 23 bpm). To end, ICV infusion of aCSF increased HR by 18 ± 3 bpm. These results suggest that the NaCl−induced pressor response is largely attributed to Na+. However, Na+ alone cannot fully account for the NaCl−induced pressor response. NIH R01 HL163906, HL152680, HL145875. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ischemic Conditioning Improves the Microvascular Hyperemic Response to Passive Limb Movement in Young Adults

Background: Passive limb movement (PLM) of the lower extremity is a simple and clinically relevant approach to measure peripheral microvascular health. PLM causes an acute increase in hyperemic leg blood flow (LBF) without an increase in skeletal muscle metabolism, and the hyperemic response is ~80% nitric oxide-mediated. A known therapeutic stimulus to increase large conduit artery vascular health is ischemic conditioning (IC). Whether a single session of IC can improve the hyperemic response to PLM remains unknown. Objective: To quantify the microvascular response to PLM after a single session of IC in young adults. Hypothesis: The hyperemic response to PLM, measured as a change in peak femoral artery blood flow, will be greater following IC vs. sham-IC. Methods: This was a prospective, cross-over, blinded clinical trial (NCT05935670). Young adults aged 18-30 years who were free of cardiovascular disease were recruited, and study participants completed two study visits. Participants were seated in a Biodex dynamometer and superficial femoral artery resting blood flow and diameter were measured in the dominant leg using ultrasonography. The dynamometer then passively moved the knee 90 degrees at a frequency of 1 Hz for a single PLM while blood flow was continuously measured. The ΔLBF was calculated as the absolute (ml/min) and relative (% change) difference in LBF from rest to peak. Participants were then randomized to receive either IC or sham-IC, and the vascular assessor was blinded to the condition. For IC, the cuff was placed around the proximal dominant thigh and repetitively inflated to 225 mmHg for 5 min then deflated for 5 min, for a total of 5 cycles. For sham-IC, the thigh cuff was inflated to only 25 mmHg. Fifteen minutes after IC or sham-IC the hyperemic response to PLM was re-assessed. The pre-/post- change in the PLM hyperemic response was calculated as the difference from pre- vs. post-IC or sham-IC. Statistical analysis included one-sided paired t-tests. Results: Seven individuals (3 female, age 26 ± 4 years old) completed the study. Compared to pre-IC, the relative peak hyperemic response to PLM was augmented post-IC (%ΔLBF = 89 ± 42% pre- vs. 136 ± 49% post-IC, p=0.001). Conversely, there was no change in the relative peak hyperemic response in the sham-IC condition (%ΔLBF = 108 ± 61% pre- vs. 108 ± 77% post-sham-IC, p=0.50). The pre-/post- change score of absolute peak hyperemic response to PLM was also higher after IC vs. sham-IC (change in ΔLBF = 50 ± 78 IC ml/min vs. -44 ± 127 ml/min sham-IC, p = 0.03). Conclusion: These results show an improvement in the peripheral microvascular response to PLM following IC. Future studies should examine the mechanistic pathways responsible for an improved PLM response as well as the potential benefits of IC on microvascular health in clinical populations with underlying peripheral microvascular dysfunction. AAW was supported by the National Heart, Lung and Blood Institute (T32HL13464) and Cardiovascular Center’s A.O. Smith Fellowship Scholars Program. Research was supported by the Eunice Kennedy Shriver National Institute of Child Health &amp; Human Development R01-HD099340 (ASH and MJD) and R01-HD112258 (MJD and ASH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

What Is the Role of the Carotid Baroreflex in Exaggerating the Exercise Pressor Reflex in Male UCD-Type 2 Diabetes Mellitus Rats?

Previous studies have shown that exercise evokes an excessive increase in blood pressure in individuals with type 2 diabetes mellitus (T2DM), which is mediated, in part, by an altered exercise pressor reflex. Importantly, in healthy individuals the arterial baroreflex modulates the pressor response to exercise; however, the effects of T2DM on this modulatory effect of the baroreflex remain unclear. Therefore, the purpose of this study was to characterize the arterial baroreflex function in T2DM rats and to determine whether the carotid baroreflex plays a role in exaggerating the exercise pressor reflex. We hypothesized that T2DM rats would present a baroreflex dysfunction that likely contributes to the exaggerated pressor response during muscle contraction. Experiments were performed on adult (8 ± 2 months old), male University of California Davis (UCD)-T2DM ( n=7; body weight: 640 ± 43 g) and healthy Sprague-Dawley rats ( n=3; body weight: 485 ± 29 g). Female rats were not included in this study because they become diabetic when they are much older (&gt;10 months old). Cardiac baroreflex function was characterized in anesthetized T2DM and healthy rats using the modified Oxford technique, which involved sequential bolus infusions of sodium nitroprusside (10 μg/kg) and phenylephrine (10 μg/kg) to induce blood pressure decreases and increases, respectively. Overall cardiac baroreflex gain (i.e., slope of the relationship between systolic blood pressure and R-R interval) was calculated using logistic regression, while gains to blood pressure falling and rising were calculated separately using piecewise and linear regression. The role of the carotid baroreflex in exaggerating the exercise pressor reflex was tested by statically contracting the hindlimb muscles for 30 s after surgical sinoaortic denervation (SAD) in decerebrated T2DM ( n=1; body weight: 555 g) and healthy ( n=1; body weight: 519 g) rats. Carotid barointact T2DM ( n=8; body weight: 521 ± 38 g) and healthy rats ( n=8; body weight: 482 ± 56 g) were included as controls. The pressor responses were calculated as a change (Δ) in peak mean arterial pressure during 30 s contraction relative to baseline. Data are presented as mean ± SD. T2DM rats presented with lower overall baroreflex sensitivity (T2DM: 0.07 ± 0.02 ms/mmHg, healthy: 0.61 ± 0.81 ms/mmHg, p=0.044), as well as sensitivity to increases in blood pressure (T2DM: 0.14 ± 0.10 ms/mmHg , healthy: 0.28 ± 0.15 ms/mmHg, p=0.049) compared to healthy controls. In contrast, cardiac baroreflex gain during decreases in blood pressure were not different between groups (T2DM: 0.16 ± 0.07 ms/mmHg, healthy: 0.10 ± 0.06 ms/mmHg, p=0.109). Notably, SAD did not alter blood pressure response to muscle contraction in the T2DM rat (SAD: Δ32 mmHg vs barointact: Δ32 ± 12 mmHg), but evoked an exaggerated blood pressure response in healthy rat (SAD: Δ34 mmHg vs barointact: Δ12 ± 3 mmHg). Our preliminary findings suggest that despite an attenuated cardiac baroreflex function in T2DM rats, specifically during acute increases in blood pressure, carotid baroreflex dysfunction may not contribute significantly to the exaggerated exercise pressor reflex in diabetes. This project was supported by NIH R01 HL144723. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The midterm psychological effect of cast removal procedures in children.

This study aimed to compare the course of anxiety change in children who used headphones during cast removal with controls in midterm follow-up. Sixty-six patients who underwent forearm fracture treatment with closed reduction and long arm casting between June 2021 and March 2023 were retrospectively reviewed. Patients were divided into two groups based on the use of headphones (n=27; 21 males, 6 females; mean age: 8.0±1.8 years; range, 6 to 12 years) or not (n=39; 27 males, 12 females; mean age: 8.9±1.8 years; range, 6 to 12 years) during cast removal with an oscillating saw. Primary outcome measures included preprocedure, postprocedure, and six-month anxiety assessments with the State-Trait Anxiety Inventory. There was an acute increase in the mean state anxiety scores after the procedure, which returned to below baseline at the six-month follow-up in the headphone (31.4±8.3, 33.3±8.7, and 25.1±4.1, respectively) and control groups (34.9±11.1, 37.4±9.5, and 27.3±5.3, respectively). The mean trait anxiety scores before the procedure, after the procedure, and at six months remained similar in the headphone (33.6±3.0, 34.6±3.2, and 32.4±2.8; p>0.05) and control groups (34.1±2.7, 33.7±3.0, and 33.7±3.0, p>0.05). This study suggests that the acute anxiety during cast removal did not create anxiety sequelae in the sixth month regardless of headphone use.

Multiple cholinergic receptor subtypes coordinate dual modulation of acetylcholine on anterior and posterior paraventricular thalamic neurons.

Paraventricular thalamus (PVT) plays important roles in the regulation of emotion and motivation through connecting many brain structures including the midbrain and the limbic system. Although acetylcholine (ACh) neurons of the midbrain were reported to send projections to PVT, little is known about how cholinergic signaling regulates PVT neurons. Here, we used both RNAscope and slice patch-clamp recordings to characterize cholinergic receptor expression and ACh modulation of PVT neurons in mice. We found ACh excited a majority of anterior PVT (aPVT) neurons but predominantly inhibited posterior PVT (pPVT) neurons. Compared to pPVT with more inhibitory M2 receptors, aPVT expressed higher levels of all excitatory receptor subtypes including nicotinic α4, α7, and muscarinic M1 and M3. The ACh-induced excitation was mimicked by nicotine and antagonized by selective blockers for α4β2 and α7 nicotinic ACh receptor (nAChR) subtypes as well as selective antagonists for M1 and M3 muscarinic ACh receptors (mAChR). The ACh-induced inhibition was attenuated by selective M2 and M4 mAChR receptor antagonists. Furthermore, we found ACh increased the frequency of excitatory postsynaptic currents (EPSCs) on a majority of aPVT neurons but decreased EPSC frequency on a larger number of pPVT neurons. In addition, ACh caused an acute increase followed by a lasting reduction in inhibitory postsynaptic currents (IPSCs) on PVT neurons of both subregions. Together, these data suggest that multiple AChR subtypes coordinate a differential modulation of ACh on aPVT and pPVT neurons.