scholarly journals Autonomous initiation of pacemaking by L-type Cav1.3 calcium channels in mouse sino-atrial myocytes

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
J Louradour ◽  
I Bidaud ◽  
JY Le Guennec ◽  
M Mangoni ◽  
P Mesirca

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Ecole doctorale Background Cardiac pacemaking relies on the spontaneous electrical activity in the right atrium of sino-atrial myocytes (SANCs). Automaticity in SANCs results from a robust interplay of membrane ion channels activity and intracellular calcium dynamics. However, only a fraction of isolated SANCs exhibit rhythmic firing, whereas most SANCs show irregular (dysrhythmic) firing or remain dormant. Purpose To study the capability of L-type Cav1.3 calcium channels to initiate automaticity in dormant SANCs under β-adrenergic stimulation, we used a knock-in mouse strain in which the sensitivity of Cav1.2 α1 subunits to dihydropyridines (DHP) was inactivated (Cav1.2DHP-/-). Methods We performed current and voltage-clamp recordings on isolated SANCs under isoprenaline (ISO, 100 nM) and in the absence or presence of the DHP blocker Nifedipine (Nife, 3 µM). Results Nife significantly reduced the spontaneous firing under ISO perfusion in all rhythmic SANCs (ISO: 447 ± 12, ISO + Nife: 233 ± 25 bpm) and 60% of dysrhythmic SANCs (ISO: 386 ± 12, ISO + Nife: 188 ± 47 bpm) whereas it completely stopped it in the remaining 40% (295 ± 29 bpm to 0). On 25 dormant SANCs, 50% started firing after ISO perfusion (0 to 320 ± 46 bpm). Strikingly, in 75% of them, Nife totally blocked this ISO-induced firing. Interestingly, these cells exhibited a significantly slower rate and a slower slope of the diastolic depolarization under ISO perfusion compared to the remaining 25% dormant SANCs in which Nife only reduced the ISO-induced firing. Moreover, dormant SANCs showed a statistically significant increase in action potential (AP) threshold under ISO compared to dysrhythmic and rhythmic SANCs (dormant: -30.1 ± 2.5, dysrhythmic: -43.3 ± 2.3, rhythmic: -41.2 ± 2.1 mV). No significant difference was observed in the other AP parameters between dormant, dysrhythmic and rhythmic SANCs under ISO. Conclusion  Our results seem to point at a difference of expression in ionic channels (Cav1.3, HCN4) within isolated SANCs. Preliminary results on If density support this hypothesis with a lesser density in dormant SANCs compared to dysrhythmic SANCs. These results also tend to indicate that Cav1.3 channels can generate pacemaker activity autonomously, at least in a particular subpopulation of SANCs.

Crisis ◽  
2001 ◽  
Vol 22 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Andrée Fortin ◽  
Sylvie Lapierre ◽  
Jacques Baillargeon ◽  
Réal Labelle ◽  
Micheline Dubé ◽  
...  

The right to self-determination is central to the current debate on rational suicide in old age. The goal of this exploratory study was to assess the presence of self-determination in suicidal institutionalized elderly persons. Eleven elderly persons with serious suicidal ideations were matched according to age, sex, and civil status with 11 nonsuicidal persons. The results indicated that suicidal persons did not differ from nonsuicidal persons in level of self-determination. There was, however, a significant difference between groups on the social subscale. Suicidal elderly persons did not seem to take others into account when making a decision or taking action. The results are discussed from a suicide-prevention perspective.


2019 ◽  
Vol 1 (4) ◽  
pp. 133-139
Author(s):  
Yasser Hamdy ◽  
Mohammed Mahmoud Mostafa ◽  
Ahmed Elminshawy

Background: Functional tricuspid valve regurgitation secondary to left-sided valve disease is common. DeVega repair is simple, but residual regurgitation with subsequent impairment of the right ventricular function is a concern. This study aims to compare tricuspid valve repair using DeVega vs. ring annuloplasty and their impact on the right ventricle in the early postoperative period and after six months. Methods: This is a prospective cohort study of 51 patients with rheumatic heart disease who underwent tricuspid valve repair for secondary severe tricuspid regurgitation. Patients were divided into two groups: group A; DeVega repair (n=34) and group B; ring annuloplasty repair (n=17). Patients were assessed clinically and by echocardiography before discharge and after six months for the degree of tricuspid regurgitation, right ventricular diameter and tricuspid annular plane systolic excursion (TAPSE). Results: Preoperative echocardiographic assessment showed no difference in left ventricular end-systolic diameter, end-diastolic diameter, ejection fraction and right ventricular diameter, however; group A had significantly better preoperative right ventricular function measured by TAPSE (1.96 ± 0.27 vs1.75 ± 0.31 cm; p=0.02). Group B had significantly longer cardiopulmonary bypass time (127.65 ± 13.56 vs. 111.74 ± 18.74 minutes; p= 0.003) and ischemic time (99.06 ± 11.80 vs. 87.15 ± 16.01 minutes; p= 0.009). Pre-discharge, there was no statistically significant difference in the degree of tricuspid regurgitation, but the right ventricular diameter was significantly lower in group B (2.66 ± 0.41 and 2.40 ± 0.48 cm; p=0.049). After six months of follow up, the degree of tricuspid regurgitation (p= 0.029) and the right ventricular diameter were significantly lower in the ring annuloplasty group (2.56 ± 0.39 and 2.29 ± 0.44 cm; p=0.029). Although there was a statistically significant difference in preoperative TAPSE, this difference disappeared after six months. Conclusion: Both DeVega and ring annuloplasty techniques were effective in the early postoperative period, ring annuloplasty was associated with lesser residual regurgitation and better right ventricular remodeling in severe functional tricuspid regurgitation than DeVega procedure after 6-months of follow up.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Velarie Ansu ◽  
Stephanie Dickinson ◽  
Alyce Fly

Abstract Objectives To determine which digit and hand have the highest and lowest skin carotenoid scores, to compare inter-and-intra-hand variability of digits, and to determine if results are consistent with another subject. Methods Two subjects’ first(F1), second(F2), third(F3) and fifth(F5) digits on both hands were measured for skin carotenoids with a Veggie Meter, for 3 times on each of 18 days over a 37-day period. Data were subjected to ANOVA in a factorial treatment design to determine main effects for hand (2 levels), digits (4), and days (18) along with interactions. Differences between digits were determined by Tukey's post hoc test. Results There were significant hand x digit, hand x day, digit x day, and hand x digit x day interactions and significant simple main effects for hand, digit, and day (all P < 0.001). Mean square errors were 143.67 and 195.62 for subject A and B, respectively, which were smaller than mean squares for all main effects and interactions. The mean scores ± SD for F1, F2, F3, and F5 digits for the right vs left hands for subject A were F1:357.13 ± 45.97 vs 363.74 ± 46.94, F2:403.17 ± 44.77 vs. 353.20 ± 44.13, F3:406.76 ± 43.10 vs. 357.11 ± 45.13, and F5:374.95 ± 53.00 vs. 377.90 ± 47.38. For subject B, the mean scores ± SD for digits for the right vs left hands were F1:294.72 ± 61.63 vs 280.71 ± 52.48, F2:285.85 ± 66.92 vs 252.67 ± 67.56, F3:268.56 ± 57.03 vs 283.22 ± 45.87, and F5:288.18 ± 34.46 vs 307.54 ± 40.04. The digits on the right hand of both subjects had higher carotenoid scores than those on the left hands, even though subjects had different dominant hands. Subject A had higher skin carotenoid scores on the F3 and F2 digits for the right hand and F5 on the left hand. Subject B had higher skin carotenoid scores on F5 (right) and F1 (left) digits. Conclusions The variability due to hand, digit, and day were all greater than that of the 3 replicates within the digit-day for both volunteers. This indicates that data were not completely random across the readings when remeasuring the same finger. Different fingers displayed higher carotenoid scores for each volunteer. There is a need to conduct a larger study with more subjects and a range of skin tones to determine whether the reliability of measurements among digits of both hands is similar across the population. Funding Sources Indiana University.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 526.1-526
Author(s):  
L. Nacef ◽  
H. Riahi ◽  
Y. Mabrouk ◽  
H. Ferjani ◽  
K. Maatallah ◽  
...  

Background:Hypertension, diabetes, and dyslipidemia are traditional risk factors of cardiac events. Carotid ultrasonography is an available way to detect subclinical atherosclerosis.Objectives:This study aimed to compare the intima-media thickness in RA patients based on their personal cardiovascular (CV) history of hypertension (hypertension), diabetes, and dyslipidemia.Methods:The present study is a prospective study conducted on Tunisian RA patients in the rheumatology department of Mohamed Kassab University Hospital (March and December 2020). The characteristics of the patients and those of the disease were collected.The high-resolution B-mode carotid US measured the IMT, according to American Society of Echocardiography guidelines. The carotid bulb below its bifurcation and the internal and external carotid arteries were evaluated bilaterally with grayscale, spectral, and color Doppler ultrasonography using proprietary software for carotid artery measurements. IMT was measured using the two inner layers of the common carotid artery, and an increased IMT was defined as ≥0.9 mm. A Framingham score was calculated to predict the cardiovascular risk at 10-year.Results:Forty-seven patients were collected, 78.7% of whom were women. The mean age was 52.5 ±11.06 [32-76]. The rheumatoid factor (RF) was positive in 57.8% of cases, and anti-citrullinated peptide antibodies (ACPA) were positive in 62.2% of cases. RA was erosive in 81.6% of cases. Hypertension (hypertension) was present in 14.9% of patients, diabetes in 12.8% of patients, and dyslipidemia in 12.8% of patients. Nine patients were active smokers. The mean IMT in the left common carotid (LCC) was 0.069 ±0.015, in the left internal carotid (LIC) was 0.069 ±0.015, in the left external carotid (LEC) was 0.060 ±0.023. The mean IMT was 0.068 ±0.01 in the right common carotid (RCC), 0.062 ±0.02 in the right internal carotid (RIC), and 0.060 ±0.016 in the right external carotid (REC). The IMT was significantly higher in the left common carotid (LCC) in patients with hypertension (p=0.025). There was no significant difference in the other ultrasound sites (LIC, LEC, RCC, RIC, and REC) according to the presence or absence of hypertension. The IMT was also significantly increased in patients with diabetes at LCC (p=0.017) and RIC (p=0.025). There was no significant difference in the IMT at different ultrasound sites between patients with and without dyslipidemia.Conclusion:Hypertension was significantly associated with the increase in IMT at the LCC level in RA patients. Diabetes had an impact on IMT in LCC and RIC. However, dyslipidemia did not affect the IMT at the different ultrasound sites.References:[1]S. Gunter and al. Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis. Clinical and Experimental Rheumatology 2018; 36: Clinical E.xperimental.[2]Aslan and al. Assessment of local carotid stiffness in seronegative and seropositive rheumatoid arthritis. SCANDINAVIAN CARDIOVASCULAR JOURNAL, 2017.[3]Martin I. Wah-Suarez and al, Carotid ultrasound findings in rheumatoid arthritis and control subjects: A case-control study. Int J Rheum Dis. 2018;1–7.[4]Gobbic C and al. Marcadores subclínicos de aterosclerosis y factores de riesgo cardiovascular en artritis temprana. Subclinical markers of atherosclerosis and cardiovascular risk factors in early arthritis marcadores subclínicos de aterosclerose e fatores de risco cardiovascular na artrite precoce.Disclosure of Interests:None declared


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
D Rocha Castellanos ◽  
A Lopez Mendez ◽  
M Fernando Perez Paz ◽  
S Pothuru ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background- Patients with small Abdominal Aortic Aneurysms are managed with surveillance as there is currently insufficient evidence to recommend surgical aneurysm repair. Hence, there is a dire need and interest in pharmacotherapy like tetracycline antibiotics to reduce the need for aneurysm repair. Purpose- To determine the efficacy and safety of doxycycline in the management of small abdominal aortic aneurysms. Methods- Electronic databases (PubMed, Scopus, Embase, Cochrane) were searched until 25th November 2020.The primary outcomes were the mean difference (MD) in aneurysm diameter and the odds ratio (OR) calculated to compare the number of individuals referred to Abdominal aortic aneurysm repair in each group. Results- A total of three studies with 572 participants (Doxycycline = 290; Placebo = 282 ) were included in our analysis. Average follow up was a period of 18 months. For AAA expansion, the combined results demonstrated a statistically significant mean difference in expansion rates favoring the placebo groups over the intervention (WMD-0.75, 95%CI 0.12-1.38; p = 0.02;I2 = 0%) There was no statistically significant difference in the efficacy and safety of doxycycline as opposed to placebo groups for referral to AAA surgery (OR 1.01, 95%CI 0.61-1.69; p = 0.96, I2 = 0%) and all-cause mortality(OR 0.51; 95%CI 0.18-1.43; p = 0.20, I2 =0%) Conclusion- Amongst patients with small abdominal aortic aneurysms, doxycycline did not significantly reduce aneurysm growth. Abstract Figure. A) AAA expansion B)Surgery C)Mortality


2021 ◽  
pp. 1-8
Author(s):  
Sevde Aksu ◽  
Pelin Palas Karaca

<b><i>Aim:</i></b> The research was conducted as a randomized controlled pilot study to evaluate the effects of reflexology on lactation in mothers who delivered by cesarean section (CS). <b><i>Methods:</i></b> A single-blind randomized controlled experimental study was conducted with a total of 60 postpartum women in the reflexology application (<i>n</i> = 30) and control groups (<i>n</i> = 30). After the CS, the mothers in the control group were given approximately 3-h routine nursing care after recovering from the effects of anesthesia; the introductory information form was applied, and the Breastfeeding Charting System and Documentation Tool (LATCH) and visual analog scale (VAS) for the signs of the onset of lactation were implemented on the first and second days. Reflexology was applied to the women in the intervention group after an average of 3 h following the mother’s condition had become stable and she had recovered from the effects of anesthesia. Reflexology was applied a total of 20 min – 10 min for the right foot, 10 min for the left foot – twice a day with 8-h intervals on the first and second days after CS. After the last reflexology application, the LATCH and VAS for the signs of the onset of lactation were applied. <b><i>Results:</i></b> Of the women, 70% breastfed their babies within 60 min after delivery; 46.7% of the mothers received breastfeeding training and 81.7% needed support for breastfeeding after the CS. The LATCH breastfeeding scores of the women in the intervention group on both days were significantly higher compared to those of the women in the control group (<i>p</i> &#x3c; 0.001). On the first day after the CS, apart from breast pain, there was no significant difference between the two groups in terms of breast heat and breast tension (<i>p</i> &#x3e; 0.05). On the second day after the CS, apart from breast tension, there was no significant difference between the groups in terms of breast heat and breast pain (<i>p</i> &#x3c; 0.05). In the study, women in the intervention group were found to have higher scores in terms of all three symptoms compared to the control group (<i>p</i> &#x3c; 0.05). <b><i>Conclusions:</i></b> In the study, it was determined that LATCH scores and signs of the onset of breastfeeding increased in the mothers who received reflexology after CS.


1996 ◽  
Vol 24 (2) ◽  
pp. 151-158 ◽  
Author(s):  
F. Barbara Orlans

Attitudes toward the Three Rs concept of refinement, reduction and replacement in the United States in research and education are widely divergent. Positive responses have come from several sources, notably from four centres established to disseminate information about alternatives. Funding sources to support work in the Three Rs have proliferated. The activities of institutional oversight committees have resulted in the nationwide implementation of important refinements. In the field of education, student projects involving pain or death for sentient animals have declined, and the right of students to object to participation in animal experiments on ethical grounds has been widely established. However, there is still a long way to go. Resistance to alternatives is deep-seated within several of the scientific disciplines most closely associated with animal research. The response of the National Institutes of Health to potentially important Congressional directives on the Three Rs has been unsatisfactory. The prestigious National Association of Biology Teachers, which at first endorsed the use of alternatives in education, later rescinded this policy, because of opposition to it. An impediment to progress is the extreme polarisation of viewpoints between the biomedical community and the animal protectionists.


Author(s):  
Graziela Maria Martins-Moreira ◽  
Alessandra Spada Durante

Abstract Introduction Good hearing in pilots, including central auditory skills, is critical for flight safety and the prevention of aircraft accidents. Pure tone audiometry alone may not be enough to assess hearing in the members of this population who, in addition to high noise levels, routinely face speech recognition tasks in non-ideal conditions. Objective To characterize the frequency-following response (FFR) of a group of military pilots compared with a control group. Methods Twenty military pilots in the Study Group and 20 non-pilot military personnel, not exposed to noise in their work, in the Control Group, all with normal hearing, aged between 30 and 40 years old, completed a questionnaire to assess their hearing habits, and their FFRs were measured with a /da/ syllable (duration 40 milliseconds, speed 10.9/s), at 80 dB NA in the right ear. All procedures were approved by the ethical committee of the institution. Statistical analysis was performed using the t-Student or Mann-Whitney tests for quantitative variables, and the Fisher or chi-squared tests for qualitative variables, and a value of p < 0.05 was considered to be statistically significant. Results There was no significant difference between the groups regarding auditory habits. In the FFR, wave amplitudes A (p = 0.01) and C (p = 0.04) were significantly lower in the Study Group. Conclusion Working as a military pilot can be a crucial factor in determining an individual's typical FFR pattern, demonstrated in the present study by statistically significant reductions in the amplitudes of the A and C waves.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric Salmon ◽  
Mohamed Ali Bahri ◽  
Alain Plenevaux ◽  
Guillaume Becker ◽  
Alain Seret ◽  
...  

AbstractThe purpose of this exploratory research is to provide data on synaptopathy in the behavioral variant of frontotemporal dementia (bvFTD). Twelve patients with probable bvFTD were compared to 12 control participants and 12 patients with Alzheimer’s disease (AD). Loss of synaptic projections was assessed with [18F]UCBH-PET. Total distribution volume was obtained with Logan method using carotid artery derived input function. Neuroimages were analyzed with SPM12. Verbal fluency, episodic memory and awareness of cognitive impairment were equally impaired in patients groups. Compared to controls, [18F]UCBH uptake tended to decrease in the right anterior parahippocampal gyrus of bvFTD patients. Loss of synaptic projections was observed in the right hippocampus of AD participants, but there was no significant difference in [18F]UCBH brain uptake between patients groups. Anosognosia for clinical disorder was correlated with synaptic density in the caudate nucleus and the anteromedial prefrontal cortex. This study suggests that synaptopathy in bvFTD targets the temporal social brain and self-referential processes.


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