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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Peptídeo natriurético atrial em um modelo de obesidade e hipertensão induzidas por dieta em ratas ovariectomizadas

Andrade, Everaldo Nery de 05 February 2011 (has links)
Submitted by Flávia Sousa (flaviabs@ufba.br) on 2013-04-15T12:48:18Z No. of bitstreams: 1 2010 - Mestrado PMPGCF - ENA.pdf: 9239730 bytes, checksum: 84722fdac879f8ba5cb909b26a109cc0 (MD5) / Approved for entry into archive by Flávia Sousa(flaviabs@ufba.br) on 2013-04-15T12:51:08Z (GMT) No. of bitstreams: 1 2010 - Mestrado PMPGCF - ENA.pdf: 9239730 bytes, checksum: 84722fdac879f8ba5cb909b26a109cc0 (MD5) / Made available in DSpace on 2013-04-15T12:51:08Z (GMT). No. of bitstreams: 1 2010 - Mestrado PMPGCF - ENA.pdf: 9239730 bytes, checksum: 84722fdac879f8ba5cb909b26a109cc0 (MD5) Previous issue date: 2011-02-05 / CNPq, CAPES, FAPESB / Introdução e objetivos: A obesidade é uma doença complexa, multifatorial, de proporções epidêmicas e é o principal fator de risco para o desenvolvimento da hipertensão arterial. Na pós-menopausa ocorre um aumento da incidência de obesidade central e hipertensão. Todavia, os mecanismos envolvidos nesta associação não estão esclarecidos. Os peptídeos natriuréticos podem participar da gênese desta fisiopatologia, pois permitem a redução da pressão arterial e evitam a hipertrofia cardíaca. Desta forma, indivíduos obesos apresentam baixos níveis plasmáticos de peptídeo natriurético atrial (ANP) e alta quantidade de receptores natriuréticos de clearance (NPR-C) que favorecem o desenvolvimento de hipertensão arterial e hipertrofia cardíaca. Assim, o objetivo deste projeto foi estudar o papel do sistema de peptídeos natriuréticos na patogênese da hipertensão e da obesidade induzidas por dieta hipercalórica utilizando ratas ovariectomizadas. Metodologia: Foram utilizadas 30 ratas Wistar pesando entre 150-200g. As ratas foram ovariectomizadas ou sham-operadas. Os animais receberam as seguintes dietas: dieta de alto teor de carboidrato ou dieta com alto teor de lipídeos ou dieta controle. Foram mensuradas a massa corporal, a pressão arterial durante 24 semanas. Em seguida, as ratas foram sacrificadas e o sangue e os tecidos foram removidos para análises posteriores. Foram realizadas: dosagem de ANP por radioimunoensaio, mensuração do diâmetro dos cardiomiócitos por análise morfológica e histológica de ventrículos e, reação em cadeia da polimerase para determinação da expressão de ANP e seus receptores em rins, tecido adiposo e coração. Resultados: As ratas ovariectomizadas sob dieta hiperlipídica mostraram aumento do peso corporal, da soma total de gorduras, da gordura visceral mesentérica e parametrial, pressão sanguínea sistólica e média. A pressão arterial sistólica e média foi correlacionada positivamente com o aumento do peso corporal nas ratas sob dieta hiperlipídica. Além disso, estas ratas mostraram menor expressão gênica de ANP cardíaco e plasmático e maior expressão gênica de NPR-C no tecido adiposo e renal do que o grupo controle. Observou-se ainda uma correlação inversa entre a expressão gênica de ANP ventricular e o peso cardíaco e correlação positiva entre o aumento da expressão gênica de NPR-C e a elevação da pressão arterial nas ratas ovariectomizadas sob dieta hiperlípidica. A maior razão da massa cardíaca/corporal, a diminuição do lúmen das câmeras cardíacas, o aumento da espessura do miocárdio e do diâmetro dos cardiomiócitos ventriculares sugerem hipertrofia cardíaca concêntrica nas ratas ovariectomizadas sob dieta hiperlipídica. Conclusão: Estes dados mostram que a combinação da ovariectomia com a dieta hiperlipídica favorece o desenvolvimento da obesidade, aumento da pressão arterial e hipertrofia cardíaca. Estes resultados sugerem que a redução da atividade do sistema de peptídeos natriuréticos pode ser um dos mecanismos envolvidos não somente no aumento da pressão arterial, mas também na hipertrofia cardíaca associada com a obesidade em ratas ovariectomizadas. / Vitória da Conquista - BA
32

Eventos cardíacos decorrentes da infusão contínua de cloridrato de amiodarona: implicações para o enfermeiro / Cardiac events originated from the continuous infusion of amiodarone hydrochloride: consequences for the nurse

Elbanir Rosangela Ferreira de Sousa 19 February 2014 (has links)
O objeto de estudo são os eventos cardíacos resultantes da infusão contínua de cloridrato de amiodarona em pacientes que evoluíram com fibrilação atrial em pós-operatório de cirurgia cardíaca. Os objetivos foram descrever as características dos pacientes que receberam infusão contínua de cloridrato de amidoarona, apresentar a prevalência de bradicardia e hipotensão encontrada nos pacientes que receberam infusão contínua de cloridrato de amiodarona e discutir as implicações dos achados para a prática dos enfermeiros a partir da prevalência encontrada de bradicardia e hipotensão decorrente da infusão contínua desta substância. Trata-se de um estudo transversal, retrospectivo, documental, por meio de análise de prontuários e avaliação quantitativa dos mesmos. Desenvolvida em uma unidade de pós-operatório de cirurgia cardíaca em um hospital universitário pertencente à rede sentinela no município do Rio de Janeiro. Foi considerado hipotensão em presença de PAS menor que 90 mmHg e bradicardia em presença de frequência cardíaca menor que 60 bpm. As variáveis que caracterizavam a população do estudo e as aferições de pressão arterial e frequência cardíaca foram transcritas para um instrumento de coleta de dados dos anos de 2010 e 2011, gerando 1782 horas de infusão contínua de cloridrato de amiodarona em 27 pacientes cirúrgicos (10,50%). Tratou-se de uma população predominantemente feminina, com idade a cima de 60 anos, período de internação superior a uma semana, apresentava hipertensão arterial prévia (59,26%), era portadora de fibrilação atrial (55,56%) e o diagnóstico cirúrgico de revascularização do miocárdio com circulação extracorpórea foi predominante (70,37%). Os dados mostram que 85,19% dos pacientes eram portadores de pelo menos um fator de risco, 70,37% apresentavam dois fatores de risco e 55,55% apresentavam três fatores de risco para desenvolver fibrilação atrial no pós-operatório de cirurgia cardíaca. Foi encontrada uma prevalência de 85,19% pacientes que apresentaram bradicardia, 66,67% apresentaram hipotensão e 59,26% apresentaram tanto bradicardia como hipotensão. Foram 160 episódios de bradicardia com 6,40 episódios por paciente e 77 episódios de hipotensão com 4,2 por paciente. A bradicardia ocorreu principalmente entre 48 e 72 horas do inicio da infusão. Já a hipotensão aumentou progressivamente nas primeiras 48 horas de infusão. Na presença de bradicardia a intervenção mais frequente foi redução da vazão de amiodarona já na presença de hipotensão, a manutenção de infusão de noradrenalina foi a conduta mais regular. Como estratégia de melhoria para segurança do paciente, foram elaboradas condutas como método de barreira para prevenção de eventos adversos como a bradicardia e hipotensão. Os principais cuidados de enfermagem a serem implementados pelo enfermeiro foram o levantamento de fatores de risco para a fibrilação atrial, a detecção da fibrilação atrial, a manutenção de monitorização cardíaca contínua, aferição horária do ritmo cardíaco e o controle da frequência cardíaca e pressão arterial, objetivando intervir precocemente em presença de hipotensão ou bradicardia. / The subject-matter of the following study is the cardiac events that are consequences from the continuous infusion of amiodarone hydrochloride into patients that developed atrial fibrillation in a postoperative care from a cardiac surgery. The aims of the study are: to describe the characteristics of the patients that received continuous infusion of amiodarone hydrochloride; to present the prevalence of bradycardia and hypotension in the patients that received continuous infusion of amiodarone hydrochloride; and to discuss the implications of the findings for the practice of nurses from the prevalence of bradycardia and hypotension that stemmed from the continuous infusion of amiodarone hydrochloride. This is a cross-sectional, retrospective, documentary study through the analysis and quantitative evaluation of medical records. It was developed in a cardiac surgery postoperative unit in a university hospital that belongs to the Rede Sentinela in the City of Rio de Janeiro. Hypotension was defined as the presence of a systemic arterial blood pressure (ABP) lower than 90 mmHg and bradycardia as the presence of a heart rate below 60 bpm. The variables that characterized the population of the study and the measuring of arterial blood pressure and heart rate were transcribed into a data collection instrument through the years 2010 and 2011, creating 1782 hours of continuous infusion of amiodarone hydrochloride into 27 surgical patients (10,50%). The population of the study was mainly composed of women over 60 years old, with an admission over a week period, they showed pre-existing arterial hypertension (58,26%) and have atrial fibrillation (55,56%) and the surgical diagnosis of myocardium revascularization with extracorporeal circulation was predominant (70,37%). The data showed that 85,19% of the patients were carriers of at least one risk factor, 70,37% showed two risk factors and 55,55% showed three risk factors to develop atrial fibrillation in the postoperative of a cardiac surgery. It was found a predominance of 85,19% patients that showed bradycardia, 66,67% showed hypotension and 59,29% showed bradycardia as well as hypotension. There were 160 bradycardia episodes in a rate of 6,40 episodes per patients and 77 hypotension in a rate of 4,2 episodes per patients. The bradycardia happened mainly between the 48 and 72 hours after the infusion. Now, the hypotension increased progressively in the first 48 hours after the infusion. In the presence of bradycardia the medical intervention most frequent was the reduction of the amiodarone flow rate, while in the presence of hypotension the continuity of the norepinephrine infusion was the most common conduct. As strategy to improve the patient safety, conducts were devised as barrier method to prevent adverse events such as the bradycardia and hypotension. The main nursing care implemented by the nurse were the survey of risk factors to the atrial fibrillation, the detection of atrial fibrillation, the continuity of the continuous cardiac monitoring, hourly measuring of the heart rate and the control of the heart rate and arterial blood pressure, in order for a earlier medical intervention in the presence of hypotension or bradycardia.
33

Fibrilação atrial e demência: estudo de base populacional no distrito do Butantã, São Paulo / Atrial fibrillation and dementia: a population-based study in the Butantã district, São Paulo

Liz Andrea Kawabata Yoshihara 06 October 2008 (has links)
INTRODUÇÃO: O aumento da proporção de idosos implica estudar os determinantes dos principais agravos associados ao envelhecimento como a demência, principalmente a associada à doença cerebrovascular. Um fator de risco relevante para doença cerebrovascular é a freqüência de fibrilação atrial crônica. O São Paulo Health and Ageing Study com base populacional para estudo de distúrbio cognitivo e demência é uma oportunidade única para verificar a prevalência de fibrilação atrial e de sua associação com demência. MÉTODOS: Estudo transversal, por arrolamento de 1524 idosos com 65 anos ou mais estudo acima, no distrito do Butantã, cidade de São Paulo. O diagnóstico de fibrilação atrial foi feito com o eletrocardiograma de repouso de doze derivações e o de demência foi feito utilizando-se o protocolo do Research Group of Dementia 10/66. Estudaram-se variáveis sócio-econômicas e fatores de risco cardiovascular como hipertensão, diabetes, dislipidemia e obesidade. RESULTADOS: A amostra estudada tinha idade média de 72,2 anos, era predominantemente feminina, branca, casada, de baixa escolaridade e renda. A prevalência de fibrilação atrial associou-se ao aumento da idade e foi de 1,9% para o sexo feminino e 3,1% para o sexo masculino, com prevalência para ambos os sexos ajustada para idade de 2,7%. A prevalência de demência também se associou ao aumento da idade e sua prevalência idade ajustada foi de 4,9%, maior em mulheres (4,8%) do que em homens (3,6%). A razão de chances ajustada para idade para a associação de fibrilação atrial e demência foi de 2,88 (Intervalo de Confiança, IC 95% - 0,98 8,40) para ambos os sexos sendo e, de 1,50 (IC95% - 0,19 11,83) para homens e 4,48 (IC95% - 1,23 16,29) para mulheres. Encontrou-se maior risco de demência entre mulheres com fibrilação atrial (17,7%) do que entre os participantes do mesmo sexo sem demência (4,6%) Outras alterações no eletrocardiograma de repouso com interesse foram determinadas como com área inativa (código de Minnesotta q1- q2) de: 9,1% nas mulheres e 16,6% nos homens; e também bloqueio de ramo esquerdo de 3,3%, nas mulheres 3,0% e nos homens 3,6%. CONCLUSÃO: Mulheres idosas com fibrilação atrial têm diagnóstico de demência quase quatro vezes mais do que aquelas em ritmo sinusal / INTRODUCTION: The growing aging population proportion makes us study the most important illness related with aging of the population as dementia, specially the dementia associated to stroke. Atrial fibrillation is a main risk factor with cerebrovascular disease. The São Paulo Heath and Ageing Study a population based study for cognitive disturb and dementia is an unique opportunity to verify the atrial fibrillation prevalence and its association with dementia. Methods: This is a cross-sectional study. The population of this study was composed by 1,524 elderly people, over 65 years of age, covered by the Health Program Family in the Butantã district, São Paulo, who were recruited door by door. The diagnosis of atrial fibrillation was made using a twelve lead resting electrocardiogram and the diagnosis of dementia was made by the protocol of Research Group of Dementia 10/66. We studied socio economic variables and cardiovascular risk factors as hypertension, diabetes, dislipidemia and obesity. RESULTS: The studied population had a mean age of 72.2 years old and was predominantly female, white, married and of low educational and financial status. We found that atrial fibrillation prevalence increased throughout age-strata and was of 1.9% among the females and 3.1% among the males, and age-adjusted prevalence of 2.7%. The prevalence of dementia also increases with age and its ageadjusted prevalence was of 4.9%, greater among the females (4.8%) than among the males (3.6%). The odds ratio age-adjusted for the association of atrial fibrillations and dementia was of 2.88 (Confidence interval, 95% CI 0.98 8.40) for both sex: 1.50 among men (95% CI 0.19 11.83), and 4.48 among women (95% CI 1.23 16.29). We found a higher risk of dementia among the female with atrial fibrillation (17.7%) than among female participants without atrial fibrillation (4.6%). Other resting electrocardiogram alterations were determined as previous inactive areas (Minnesotta Code q1-q2) of 12.4%: among the females of 9.1% and among the males of 16.6%. The frequency of left bundle-branch block was of 3.3%: among the females of 3.0% and among the males of 3.6% .CONCLUSION: Elderly women with atrial fibrillation had the diagnosis of dementia almost four times greater than that of women with sinus rhythm
34

Inhibition of pulsatile luteinizing hormone release by atrial natriuretic peptide and brain natriuretic peptide in the ovariectomized rat

Zhang, Jin January 1990 (has links)
Atrial natriuretic peptide (ANP) of atrial myocyte origin, has been shown to play a role in the diuresis, natriuresis, and antagonism of angiotensin and vasopressin. However, it is now apparent that in addition to the production of the peptide in the heart and in its role in fluid and electrolyte homeostasis, it is also produced in the central nervous system participating in the regulation of pituitary hormone secretion. Administration of ANP through both central and peripheral routes has been shown to inhibit secretion of luteinizing hormone (LH) in the gonadectomized rat model. A better understanding of the modulatory role of ANP on LH secretion and its possible mechanisms will add to our knowledge of the effects of neuropeptides on reproductive function. Brain natriuretic peptide (BNP) is a bioactive peptide of 26 amino acid residues recently identified in porcine brain. The peptide exerts potent diuretic-natriuretic and vasorelaxant effects, in a manner similar to that of ANP. BNP has a remarkable high sequence homology to ANP, especially in the 17 amino acid ring formed by an intramolecular disulfide linkage which is required for biological activity. The presence of BNP with ANP in the mammalian brain and remarkable resemblance in their molecular structures and physiological functions implies that BNP may also exert an inhibitory effect on LH secretion like ANP. This research focused on the effects of centrally administered ANP and BNP on pulsatile LH secretion and their possible mechanisms of action in ovariectomized rats. After third ventricle infusion of ANP or BNP, inhibition of mean plasma LH level, LH pulse amplitude and pulse frequency was observed. In searching for the possible mechanisms of inhibitory effect of ANP or BNP on pulsatile LH secretion, the effect of inhibiting the endogenous opiate system with naloxone on the action of centrally administered ANP or BNP was tested. Application of naloxone reversed the inhibitory effect of ANP and BNP on mean plasma LH level and LH pulse amplitude, but in terms of pulse frequency, naloxone treatment failed to reverse the inhibitory effect of ANP or BNP. In separate experiments, pretreatment with pimozide, a dopaminergic receptor blocker, prevented the inhibitory action of ANP and BNP on LH secretion. After infusion of ANP or BNP, there were no significant decrease in mean plasma LH level, pulse amplitude and pulse frequency in the pimozide-pretreated rats. In summary, the present study shows that both ANP and BNP inhibit pulsatile LH secretion, suggesting that the inhibitory effects on LH secretion once thought to be mediated by ANP alone may be regulated through a dual mechanism involving both ANP and BNP. Furthermore, the inhibitory mechanisms may involve the interactions of ANP and BNP with central opiate system and dopaminergic system on LH secretion. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate
35

Advances in the Management of Atrial Fibrillation With a Special Focus on Non-Pharmacological Approaches to Prevent Thromboembolism: A Review of Current Recommendations

Riddle, Malini, McCallum, Richard, Ojha, Chandra Prakash, Paul, Timir Kumar, Gupta, Vineet, Baran, David Alan, Prakash, Bharat Ved, Misra, Amogh, Mares, Adriana Camila, Abedin, Moeen, Kedar, Archana, Mulukutla, Venkatachalam, Ibrahim, Ahmed, Nagarajarao, Harsha 01 December 2020 (has links)
Atrial fibrillation (AFIB) is the most common heart rhythm abnormality and is associated with significant morbidity and mortality. While the treatment of AFIB involves strategies of rate with or without rhythm control, it is also essential to strategize appropriate therapies to prevent thromboembolic complications arising from AFIB. Previously, anticoagulation was the main treatment option which exposed patients to higher than usual risk of bleeding. However, with the advent of new technology, novel therapeutic options aimed at surgical or percutaneous exclusion or occlusion of the left atrial appendage in preventing thromboembolic complications from AFIB have evolved. This review evaluates recent advances and therapeutic options in treating AFIB with a special focus on both surgical and percutaneous interventions which can reduce and/or eliminate thromboembolic complications of AFIB.
36

The right atrial pacemaker complex: The underlying mechanisms mediating the multicentric origin of atrial depolarization

Mongeon, Luc Roland January 1993 (has links)
No description available.
37

Outcomes and direct treatment costs with novel oral anticoagulants compared to clinic-monitored warfarin for stroke prevention in atrial fibrillation

Hulvershorn, Sarah Elizabeth 10 October 2014 (has links)
Objectives: To describe patient characteristics and evaluate costs and outcomes of novel oral anticoagulants compared to clinic-monitored warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation within the Scott & White Healthcare system. Methods: Patients with atrial fibrillation, CHADS₂ score ≥ 1, and a prescription claim for dabigatran, rivaroxaban, or warfarin between 2010 and 2012 were evaluated over 12 months. Patients in the warfarin cohort were enrolled in an Anticoagulation Clinic. Patients were matched 1:1 for age, CHADS₂, and gender for comparisons between groups. Baseline characteristics, medication adherence, occurrence of adverse events, and treatment costs were compared using inferential statistics. Anticoagulation control was assessed for patients in the warfarin cohort. Results: 141 and 471 patients met criteria for the novel cohort group and the warfarin group, respectively. After matching, 136 remained in each cohort. Prior to matching, compared to the warfarin cohort, the novel anticoagulant cohort had a higher proportion of male patients (63% versus 49%), and lower average CHADS₂ score (2.65 versus 3.30), while average age in both cohorts was similar (75 years). Matched cohorts had similar adherence rates (88% for novel versus 87% for warfarin). After matching, annual medication cost in 2014 US dollars for dabigatran or rivaroxaban averaged $2,658 (SD $1,494) compared to $1,066 (SD $633) for warfarin, including monitoring costs. Annual total all-cause healthcare costs averaged $23,711 (SD $22,910) for dabigatran or rivaroxaban, compared to $18,248 (SD $24,184) for warfarin. For the 95 warfarin patients with INR values, time in therapeutic range averaged 70.4%. Conclusion: Compared to clinic-monitored warfarin, more men than women were prescribed new oral anticoagulants and these patients averaged a lower CHADS₂ score. After matching, patient adherence was high and comparable between groups. Anticoagulation control for warfarin patients was similar to clinical trials. Annual medication cost was significantly greater for new oral anticoagulants than clinic-monitored warfarin, including INR monitoring costs. Total annual all-cause healthcare costs were significantly greater for patients taking new oral anticoagulants compared to warfarin, although too few adverse events occurred to draw conclusions regarding event rates and costs of ischemic stroke and major bleeds. / text
38

Occlusion of the left atrial appendage using catheter-delivered hydrogels for prevention of thromboembolic phenomena

Zimbroff, Andrew David 15 October 2014 (has links)
The Left Atrial Appendage, once thought to be "a relatively insignificant portion of cardiac anatomy," has currently been realized to possess "important pathological associations [1a]" particularly in its role in promoting serious, frequent thromboembolic events common in individuals suffering from Atrial Fibrillation. Prior approaches to mitigating these events have either required invasive procedures, proved less than fully effective, or presented with problematic sequelae of their own. This work will present a new procedure that addresses both the prevention of the thromboembolic events and the correction of the shortcomings of the major prior methods utilized. A compliant hydrogel that can conform to the geometry of the appendage is proposed as a more effective method of occluding the chamber. This material would be transported to the LAA in liquid form via a multi-lumen catheter, and then solidify within the chamber to form a solid plug. Previous research has identified a candidate hydrogel, comprised of PEG-tetra-thiol and Dextran vinyl sulfone as a candidate hydrogel for this application. Experimental work has investigated fluid properties of the material, as well as degradation and swelling properties of the material. Results from this experimentation were used for fluid transport analysis, and for evaluation of anchoring force of the hydrogel within the chamber. Finally, subfunctions of the occlusion procedure were modeled and tested. During the actual procedure, a catheter balloon will isolate the appendage from the rest of the heart. A model was developed to study interactions between the appendage and this balloon. Additionally, due to fast solidification time, hydrogel components in the surgical procedure will be mixed in a mixing chamber at the tip of the catheter. Potential mixing chamber designs were modeled, and a ternary diffusion model was developed to better understand hydrogel mixing. Prototypes for both these subfunctions were built and tested as well. Additional analysis looked at the overall occlusion procedure, and how various subfunctions interacted with each other. / text
39

A control and systems theory approach to the optimal fluid management of the post-operative cardiac patient

Akgun, A. January 1984 (has links)
No description available.
40

Characterizing the Role of Regulator of G-protein Signalling 4 as a Mediator of Sinoatrial Node and Atrial Cardiomyocyte Function

Cifelli, Carlo 14 February 2011 (has links)
Heart rate is modulated by the opposing activities of sympathetic and parasympathetic inputs to pacemaker cardiomyocytes in the sinoatrial (SA) node. Parasympathetic activity on nodal myocytes is mediated by acetylcholine-dependent stimulation of M2 muscarinic receptors and activation of Gαi/o signalling. Although, regulators of G-protein signalling (RGS) proteins are potent inhibitors of Gαi/o signalling in many tissues, the RGS protein(s) that regulate parasympathetic tone in the SA node are unknown. Our results demonstrate that RGS4 mRNA levels are higher in the SA node compared to right atrium. Conscious freely moving RGS4-null mice showed a greater extent of bradycardia in response to parasympathetic agonists compared to wild-type animals. Moreover, anaesthetized rgs4-null mice had lower baseline heart rates and greater heart rate increases following atropine administration. Retrograde-perfused hearts from rgs4-null mice also showed enhanced negative chronotropic responses to carbachol, while isolated SA node myocytes showed greater sensitivity to carbachol-mediated reduction in the action potential firing rate. Finally, rgs4-null SA node cells showed decreased levels of G-protein-coupled inward rectifying potassium (GIRK) channel desensitization, and altered modulation of acetylcholine-sensitive potassium current (IKACh) kinetics following carbachol stimulation. Taken together, our studies establish that RGS4 plays an important role in regulating sinus rhythm by inhibiting parasympathetic signalling and IKACh activity. Following these results, we predicted that loss of RGS4 expression and function will result in increased levels of parasympathetic effector activity leading to increased susceptibility to atrial fibrillation. Susceptibility to atrial fibrillation (AF) depends strongly on parasympathetic activity. Since RGS4 inhibits parasympathetic / M2-dependent Gαi/o signalling in the SA node, we explored whether changes in RGS4 levels altered the susceptibility of atrial fibrillation. We found that, RGS4 levels were decreased in atria of tachypaced dogs prior to their development of chronic AF. Moreover, in vivo ECG recordings of anaesthetized mice showed greater susceptibility to AF while optical mapping of isolated atrial preparations using a voltage-sensitive dye revealed greatly increased susceptibility to rotor formation when RGS4 was ablated. Consistent with altered parasympathetic signalling in the myocardium of rgs4-null mice, IKACh evoked by carbachol application were greater in isolated atrial myocytes from rgs4-null mice. These IKACh changes were, as expected, associated with marked action potential duration shortening in response to parasympathetic activation, but not to slower conduction velocities. Together, our findings establish that RGS4 protects atrial tissues from excess parasympathetic signalling that predispose to atrial fibrillation.

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