Abstract 1352: Gender Differences In Cardiac Repolarization In Transgenic Long QT Syndrome 2 (LQT2) Rabbits

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Katja E Odening ◽  
Mohammad Hajjiri ◽  
Michael Brunner ◽  
Peem Lorvidhaya ◽  
Lorraine Schofield ◽  
...  
Keyword(s):  
Gender Differences ◽  
Cardiac Repolarization ◽  
Adult Women ◽  
Male Adult ◽  
Clinical Events ◽  
Transgenic Rabbits ◽  
Surface Ecg ◽  
Electrophysiological Studies ◽  
Genotype Difference

Introduction: Adult women with LQT2 are at higher risk for clinical events and sudden cardiac death (SCD) than men. We have created transgenic rabbits over-expressing pore mutants of the human KvLQT1 (LQT1) and HERG (LQT2) selectively in the heart. We report the gender differences in cardiac repolarization, incidence of polymorphic VT and SCD in these cohorts. Methods: Adult female and male LQT1, LQT2, and littermate controls (ages 5 to 33 mo were similar in f/m, LQT2 were younger due to higher mortality) underwent telemetric ECG monitoring, surface ECG and in vivo electrophysiological studies under general anaesthesia with isoflurane (2–5%). Results: Monitoring data showed a steeper QT/RR slope in female (0.745 ± 0.05, n=4) than in male (0.513 ± 0.06, n=9; p<0.05) LQT2 rabbits. No significant gender differences were observed in QT/RR slopes in either LQT1 or WT rabbits. QT-, QTpeak-index and Tp-e were significantly longer in female than in male LQT2 rabbits (females, n=6: QT: 129.2% ± 3.9; QTp: 105.9% ± 2.1; Tp-e: 42.9ms ± 4.1 vs. males, n=8: QT: 117.5% ± 4.3; p<0.05; QTp: 93.5% ± 5.6, p<0.05; Tp-e: 29.5ms ± 2.9, p<0.02). EP studies revealed significantly longer atrial (AERP) and ventricular (VERP) refractory periods in LQT2 females compared to males (females, n=4: AERP: 143.3 ± 5.8 ms; VERP: 212.5 ± 22.2 ms vs. males, n=8: AERP: 102.5 ± 7.7 ms, p<0.01; VERP: 178.1 ± 7.8 ms, p<0.05). AERP and VERP were significantly longer in LQT2 females than in LQT1 females (LQT1 females, n=7: AERP: 101.4 ± 7.7 ms, p<0.01, VERP: 156.9 ± 6.2, p<0.001), whereas in male LQT rabbits this genotype difference was only found in VERP but not in AERP. Survival was significantly shorter in female LQT2 rabbits compared to LQT1 or WT controls, with 4 sudden deaths among 10 LQT2, 1 among 19 WT and no SCD in 13 LQT1 females (p<0.02). No gender difference was observed in mortality. All cases of SCD occurred after sexual maturation and two LQT2 females died during lactation. Monitoring revealed the cause of SCD was polymorphic VT. Conclusions: Monitoring of LQT rabbits reveal gender differences in LQT2 rabbits. QT/RR slope is steeper in female than in male adult LQT2 rabbits. AERP and VERP are longer in LQT2 females than in males. Finally, in LQT2 females, SCD was associated with lactation, but not pregnancy.

Abstract 1354: Estrogen predisposes prepubertal Long QT Syndrome 2 (LQT2) rabbits to cardiac arrhythmias

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Katja E Odening ◽  
Michael Brunner ◽  
Lorraine Schofield ◽  
Lenny Chaves ◽  
Xuwen Peng ◽  
...  
Keyword(s):  
Hormone Treatment ◽  
Cardiac Repolarization ◽  
Adult Women ◽  
Ecg Monitoring ◽  
Female Phenotype ◽  
Clinical Events ◽  
Surface Ecg ◽  
Male Phenotype ◽  
Electrophysiological Studies

Introduction: Adult women with LQT2 are at higher risk for clinical events and sudden cardiac death (SCD) than men. We have created transgenic LQT2 rabbits selectively over-expressing a pore mutant of the human HERG in the heart. All episodes of SCD in these LQT2 females occurred after sexual maturation. We hypothesize that sex hormones modulate cardiac repolarization and incidence of polymorphic VT in female LQT2 rabbits. Methods: In this ongoing study, prepubertally ovariectomized females were implanted with 90 day-release-pellets of estradiol (EST, 150mg), or dihydrotestosterone (DHT, 200mg), or placebo (OVX). A fourth group consisted of sham-operated females (SHAM). All groups underwent telemetric ECG monitoring, surface ECG after 30 days of hormone treatment, and in vivo electrophysiological studies (EPS) under isoflurane (2–5%) after 60 days. Results: EST steepened the QT/RR slope of prepubertal rabbits mimicking the adult LQT2 female phenotype (baseline: 0.608 ± 0.09, after 4 weeks: 0.69 ± 0.1, n=5, p<0.05; SHAM females: 0.699 ± 0.07, n=4). In contrast, DHT decreased the QT/RR slope (baseline: 0.739 ± 0.11, after 4 weeks: 0.521 ± 0.08, n=3, p=0.02). A smaller decrease was seen in OVX: 0.677 ± 0.01 vs. 0.599 ± 0.08, n=2. EST prolonged QT- and QTpeak-index compared to DHT rabbits. (EST, n=2: QT: 112.6% ± 1.5; QTp: 95.8% ± 1.6 vs. DHT, n=2: QT: 105.4% ± 4.1, p=0.07; QTp: 87.6% ± 0.9, p<0.05 vs. SHAM females, n=2: QT: 123.4% ± 9.5; QTp: 102.3% ± 2.5) EPS revealed a longer AERP and VERP in EST than in DHT rabbits - and a trend towards longer refractoriness than in OVX - reaching similarly prolonged refractoriness as in SHAM females (EST, n=2: AERP: 165.0 ± 35.4ms; VERP: 225.0 ± 25.0ms vs. DHT, n=3: AERP: 90.00 ± 5.8ms, p=0.03; VERP: 193.3 ± 8.8ms, p=0.07 vs. OVX, n=2: AERP: 125.0 ± 25.0ms, VERP: 205.0 ± 5.0ms, vs. SHAM females, n=2: AERP: 145.0 ± 5.0ms, VERP: 220.0 ± 20.0ms). One out of four EST-treated prepubertal rabbits died at the age of 96 days of spontaneous polymorphic VT. Conclusion: EST increases the QT/RR slope and prolongs QT and cardiac refractoriness mimicking the adult LQT2 female phenotype, whereas DHT decreases the QT/RR slope and shortens QT and refractoriness mimicking a male phenotype. EST predisposes prepubertal LQT2 rabbits to spontaneous polymorphic VT.

scholarly journals Inducibility, but not stability, of atrial fibrillation is increased by NOX2 overexpression in mice

2021 ◽  
Author(s):  
Alexandra S Mighiu ◽  
Alice Recalde ◽  
Klemen Ziberna ◽  
Ricardo Carnicer ◽  
Jakub Tomek ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Superoxide Production ◽  
Right Atrial ◽  
Burst Stimulation ◽  
Lv Mass ◽  
Surface Ecg ◽  
Tissue Homogenates ◽  
Genotype Difference ◽  
Left And Right

Abstract Aims Gp91-containing NADPH oxidases (NOX2) are a significant source of myocardial superoxide production. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling in animal models and predicts incident AF in humans; however, a direct causal role for NOX2 in AF has not been demonstrated. Accordingly, we investigated whether myocardial NOX2 overexpression in mice (NOX2-Tg) is sufficient to generate a favourable substrate for AF and further assessed the effects of atorvastatin, an inhibitor of NOX2, on atrial superoxide production and AF susceptibility. Methods and results NOX2-Tg mice showed a 2- to 2.5-fold higher atrial protein content of NOX2 compared with wild-type (WT) controls, which was associated with a significant (twofold) increase in NADPH-stimulated superoxide production (2-hydroxyethidium by HPLC) in left and right atrial tissue homogenates (P = 0.004 and P = 0.019, respectively). AF susceptibility assessed in vivo by transoesophageal atrial burst stimulation was modestly increased in NOX2-Tg compared with WT (probability of AF induction: 88% vs. 69%, respectively; P = 0.037), in the absence of significant alterations in AF duration, surface ECG parameters, and LV mass or function. Mechanistic studies did not support a role for NOX2 in promoting electrical or structural remodelling, as high-resolution optical mapping of atrial tissues showed no differences in action potential duration and conduction velocity between genotypes. In addition, we did not observe any genotype difference in markers of fibrosis and inflammation, including atrial collagen content and Col1a1, Il-1β, Il-6, and Mcp-1 mRNA. Similarly, NOX2 overexpression did not have consistent effects on RyR2 Ca2+ leak nor did it affect PKA or CaMKII-mediated RyR2 phosphorylation. Finally, treatment with atorvastatin significantly inhibited atrial superoxide production in NOX2-Tg but had no effect on AF induction in either genotype. Conclusion Together, these data indicate that while atrial NOX2 overexpression may contribute to atrial arrhythmogenesis, NOX2-derived superoxide production does not affect the electrical and structural properties of the atrial myocardium.

Release, Aggregation and Lysis of Human Platelets by Antilymphocyte Globulin and Antiplatelet Serum

1976 ◽  
Vol 36 (02) ◽  
pp. 411-423 ◽  
Author(s):  
Nicholas Lekas ◽  
J. C Rosenberg
Keyword(s):  
Platelet Aggregation ◽  
Gamma Globulin ◽  
Human Platelets ◽  
Plasma Medium ◽  
Release Reaction ◽  
Clinical Events ◽  
Thrombotic Complications ◽  
Platelet Release ◽  
Free Media

SummaryHuman platelets labeled with 51Cr were used to determine the contribution made by platelet lysis to the platelet release reaction and platelet aggregation induced by rabbit antihuman platelet serum (APS) and equine antihuman thymocyte globulin (ATG). Platelets were tested in both plasma (PRP) and non-plasma containing media. Antibodies directed against platelets, either as APS or ATG, induced significant amounts of platelet release and aggregation, as well as some degree of lysis, in the absence of complement. The presence of complement increased platelet lysis and aggregation, but not the release reaction. Non-immune horse gamma globulin produced different responses depending upon whether platelets were investigated in PRP or non-plasma containing media. Aggregation was seen in the latter but not the former. These differences can be explained by the presence of plasma components which prevent non-specific immune complexes from causing platelet aggregation. Since platelets in vivo are always in a plasma medium, one must be wary of utilizing data from platelet studies in synthetic plasma-free media as the basis of explaining clinical events. These observations demonstrate at least two, and possibly three, different mechanisms whereby ATG could activate platelets causing thrombotic complications and thrombocytopenia, i.e., via 1) specific and, 2) non-specific non-lytic pathways and 3) a lytic pathway.

Identity Status, Gender, and Social Comparison among Young Adults

2019 ◽  
Author(s):  
Fanny Gyberg ◽  
Ann Frisén
Keyword(s):  
Gender Differences ◽  
Young Adults ◽  
Social Comparison ◽  
Young Adulthood ◽  
Identity Status ◽  
Adult Women ◽  
Global Identity ◽  
Identity Statuses ◽  
Social Comparison Orientation ◽  
And Diffusion

The aim of this study was to investigate identity status globally and across identity domains among young Swedish adult women and men. Also, potential differences in social comparison between identity statuses were evaluated. The results showed that most of the 124 participants (50% women, Mage 33.29 years) were assigned to an achieved global identity and had made identity-defining commitments across domains. Gender differences in identity status were found in the occupational and parenthood domains. In addition, differences in social comparison orientation were found only in the parenthood domain, whereas those assigned to moratorium scored higher in social comparison than did those assigned to foreclosure and diffusion. These results bring important knowledge to our understanding of identity during young adulthood.

scholarly journals Gender Difference in Architectural and Mechanical Properties of Medial Gastrocnemius–Achilles Tendon Unit In Vivo

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 569
Author(s):  
Liqin Deng ◽  
Xini Zhang ◽  
Songlin Xiao ◽  
Baofeng Wang ◽  
Weijie Fu
Keyword(s):  
Mechanical Properties ◽  
Gender Differences ◽  
Gender Difference ◽  
Achilles Tendon ◽  
Medial Gastrocnemius ◽  
Regular Exercise ◽  
Training Experience ◽  
Exercise Habits ◽  
Vertical Stiffness

This study aims to explore whether gender differences exist in the architectural and mechanical properties of the medial gastrocnemius–Achilles tendon unit (gMTU) in vivo. Thirty-six healthy male and female adults without training experience and regular exercise habits were recruited. The architectural and mechanical properties of the gMTU were measured via an ultrasonography system and MyotonPRO, respectively. Independent t-tests were utilized to quantify the gender difference in the architectural and mechanical properties of the gMTU. In terms of architectural properties, the medial gastrocnemius (MG)’s pennation angle and thickness were greater in males than in females, whereas no substantial gender difference was observed in the MG’s fascicle length; the males possessed Achilles tendons (ATs) with a longer length and a greater cross-sectional area than females. In terms of mechanical properties, the MG’s vertical stiffness was lower and the MG’s logarithmic decrement was greater in females than in males. Both genders had no remarkable difference in the AT’s vertical stiffness and logarithmic decrement. Gender differences of individuals without training experience and regular exercise habits exist in the architectural and mechanical properties of the gMTU in vivo. The MG’s force-producing capacities, ankle torque, mechanical efficiency and peak power were higher in males than in females. The load-resisting capacities of AT were greater and the MG strain was lesser in males than in females. These findings suggest that males have better physical fitness, speed and performance in power-based sports events than females from the perspective of morphology and biomechanics.

Very high dilutions of dexamethasone inhibit its pharmacological effects in vivo

2001 ◽  
Vol 90 (04) ◽  
pp. 198-203 ◽  
Author(s):  
LV Bonamin ◽  
KS Martinho ◽  
AL Nina ◽  
F Caviglia ◽  
RGW Do Rio
Keyword(s):  
Inflammatory Cells ◽  
Experimental Models ◽  
Tumour Cells ◽  
Pharmacological Effects ◽  
Trypan Blue Exclusion ◽  
Male Adult ◽  
Trypan Blue Exclusion Method ◽  
High Dilutions ◽  
Ascitic Tumour

AbstractWe evaluated the interaction of dexamethasone 10−17 and 10−33 M (equivalent to 7cH and 15cH) with dexamethasone in pharmacological concentrations, using as experimental models: acute inflammation induced by carrageenan, Ehrlich ascitic tumour, and migration of tumour infiltrating leukocytes (TIL). Male adult BALB/c mice (n=7 per group) were used in all experiments. Carrageenan (1%) was injected into the footpad for oedema evaluation and into the peritoneal cavity (i.p.), for differential counting of inflammatory cells. Ehrlich ascitic tumour cells (107 viable cells/ml) were injected i.p. and tumour cells were counted after 6 days, by the Trypan blue exclusion method. The differential TIL was counted using smears stained by hematoxylin–eosin. Treatments were made immediately after carrageenan inoculation or once a day, during Ehrlich tumour development, until the animals were killed. Animals were treated with the following preparations: (1) phosphate buffer saline (PBS) solution; (2) dexamethasone (0.5 mg/kg for inflammation model or 4 mg/kg for tumour model) mixed with dexamethasone 7cH or 15cH; (3) dexamethasone (same doses) mixed in PBS. Homeopathic dexamethasone partially blocked the anti-inflammatory effect of pharmacological dexamethasone with regard to paw oedema (two-way ANOVA, P≤0.0008) and polymorphonuclear cell migration (χ2, P=0.0001). No important differences were observed between experimental and control groups, in relation to Ehrlich tumour cells viability or count, or bodyweight, but potentised dexamethasone restored control levels of TIL viability, compared to mice treated with pharmacological doses of dexamethasone (χ2, P≤0.001). The results demonstrate that a potentised substance may change its own pharmacological effects and suggest that ultradilutions effects act mostly on host response.

scholarly journals B-973, a Novel α7 nAChR Ago-PAM: Racemic and Asymmetric Synthesis, Electrophysiological Studies, and in Vivo Evaluation

2018 ◽  
Vol 9 (11) ◽  
pp. 1144-1148 ◽  
Author(s):  
Sumanta Garai ◽  
Krishnamohan S. Raja ◽  
Roger L. Papke ◽  
Jeffrey R. Deschamps ◽  
M. Imad Damaj ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
In Vivo Evaluation ◽  
Α7 Nachr ◽  
Electrophysiological Studies

scholarly journals Electro-mechanical and mechano-electrical interactions in healthy and drug-induced LQTS rabbit hearts

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
R Lewetag ◽  
T Hornyik ◽  
S Jacobi ◽  
R Moss ◽  
N Pilia ◽  
...  
Keyword(s):  
Longitudinal Velocity ◽  
Electrical Coupling ◽  
Qt Dispersion ◽  
Cardiac Repolarization ◽  
Mechanical Function ◽  
Regional Heterogeneity ◽  
Drug Induced ◽  
Longitudinal Contraction ◽  
German Research Foundation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): German Research Foundation Background Electrical and mechanical heterogeneities and their interactions (electro-mechanical and mechano-electrical coupling; EMC / MEC) are essential for normal cardiac function. Alterations in these can result in increased arrhythmia formation. Purpose With this study, we aim to investigate EMC and MEC under physiological and pathological conditions to better understand their roles in arrhythmia development. Methods Multi-channel ECG and TPM-MRI were used to measure regional differences in EMC in healthy ("control") and IKr-blocker E-4031 induced acute LQTS ("E-4031") rabbit hearts in vivo. MEC was studied in both groups by acutely changing mechanical function (increased preload by 6 ml/kg BW bolus of NaCl). Results In acute LQTS hearts (E-4031 10µg/kg bolus + 1µg/(kg*min) iv), cardiac repolarization was markedly prolonged compared to healthy controls, (p &lt; 0.0001; n = 13), with increased QT-dispersion (Max-Min), a marker for regional heterogeneity of repolarization (p &lt; 0.01; n = 13). Changing electrical function by E-4031 resulted in changes of mechanical features (EMC): in acute LQTS hearts, diastolic longitudinal velocity (Vz) was reduced in all basal (p = 0.003; n = 19) and 4/6 mid segments (p = 0.006; n = 19). Longitudinal diastolic TTP was prolonged significantly in 5/6 basal and 4/6 mid segments by E-4031. These alterations led to an increased apicobasal heterogeneity of longitudinal contraction duration (basal-apical Vz_dia_TTP [ms] 2.9 ± 10.6 vs. 21.1 ± 21.3; p = 0.01; n = 9). Increased preload acutely prolonged QTc in both "control" and "E-4031" hearts (‘control’ 156.6 ± 11.6 to 198.3 ± 20.3; p &lt; 0.0001 vs. ‘E-4031’ 193.9 ± 19.6 to 256.0 ± 37.5; p &lt; 0.0001; n = 13) (MEC). This effect was more pronounced in "E-4031" acute LQTS hearts than in healthy hearts (Figure 1; delta QTc [ms] ‘control’ 41.6 ± 14.9 vs. ‘E4031’ 62.1 ± 32.1; p &lt; 0.006, n = 13). QT-dispersion (Max-Min) was increased significantly upon mechanical change only in "E-4031" (‘E-4031’ 25.8 ± 5.5 to 32.7 ± 12.3; p &lt; 0.03, n = 13). Conclusion E-4031-induced changes in electrical function resulted in marked alterations in mechanical features via EMC. Similarly, acute changes in mechanical function (increased preload) resulted in electrical changes via MEC. Importantly, QT-prolonging effects of acutely increased preload, as well as its effects on regional heterogeneity of repolarization, were more pronounced in E-4031-induced acute LQTS hearts, indicating that cardiac repolarization in LQTS may be more susceptible to acute MEC effects than in healthy hearts. Acute MEC effects may thus play an additional role in LQT-related arrhythmogenesis. Abstract Figure.

Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies

2006 ◽  
Vol 190 (3) ◽  
pp. 373-382 ◽  
Author(s):  
Arlene D. Stark ◽  
Shaun Jordan ◽  
Kelly A. Allers ◽  
Robert L. Bertekap ◽  
Ruoyan Chen ◽  
...  
Keyword(s):  
Receptor Binding ◽  
The Novel ◽  
Electrophysiological Studies ◽  
Novel Antipsychotic ◽  
Functional Receptor

High Resolution Magnetic Resonance Imaging of Resected Plaque

1997 ◽  
Vol 3 (S2) ◽  
pp. 309-310
Author(s):  
D. Saloner
Keyword(s):  
Atherosclerotic Plaque ◽  
Carotid Bifurcation ◽  
Surgical Removal ◽  
Strongly Correlated ◽  
Clinical Events ◽  
Significant Events ◽  
Diseased Vessel ◽  
Clinically Significant ◽  
Substantial Interest

Atherosclerotic plaque at the carotid bifurcation is strongly correlated with the incidence of clinically significant events, such as transient ischemie attacks or stroke. Large multi-center trials have demonstrated that surgical removal of the atheroma is more effective in reducing these clinical events than is medical treatment alone. Patients are selected for surgery from an assessment of the severity of disease at the carotid bifurcation. The measure of disease severity is conventionally taken to be the degree of narrowing of the diseased vessel compared to a normal segment of vessel. However, using this criterion alone, many patients receive endarterectomy surgery who would probably not have progressed to other neurological events, while others are excluded who do progress to neurological events. For this reason, there is substantial interest in methods that could evaluate the composition of the atherosclerotic plaque in vivo, with the hope that this information would improve the predictive power of pre-surgical imaging of the diseased vessel.

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