FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2317759260> ?p ?o ?g. }

• W2317759260 abstract "Normal cardiac function is dependent on a healthy conduction system to maintain coordinated and synchronised activity. In the presence of heart failure, dyssynchronous ventricular activation due to left bundle branch block or right ventricular pacing can result in worsening symptoms and increased mortality; cardiac resynchronisation therapy in the form of biventricular pacing has therefore become an established and effective treatment. However, it also appears that right ventricular pacing can be a cause of heart failure in some individuals, even when there is no evidence of associated pre-existing cardiac disease. A better understanding of the processes leading to dyssynchrony-induced cardiomyopathy will allow better identification and treatment of patients who are at risk, and will contribute to our knowledge about heart failure in general.This PhD adopted a translational approach to cardiac dyssynchrony, by developing a novel model of atrial-synchronous ventricular pacing in adult Welsh Mountain sheep. The right ventricle was paced from the apex continuously for 3 months at a rate that was determined by the intrinsic atrial rate; this allowed the ventricular activation pattern to be altered without changing the heart rate. In parallel, a previously-developed model of rapid ventricular pacing was studied. In this model, the heart was paced continuously at a fixed rate of 210 bpm, which led to the development of symptomatic heart failure.In vivo parameters were characterised using standard clinical techniques of electrocardiography and echocardiography. Autonomic nervous system activity was investigated by examining the heart rate responses to pharmacological blockade using atropine and propranolol, and to beta-adrenergic stimulation using dobutamine. Heart rate variability was analysed in the time and frequency domains. In vitro, patch clamping studies were performed on ventricular myocytes isolated through enzymatic digestion from the interventricular septum and left ventricular free wall. Using the perforated patch current clamp technique at 37 ?C, action potential duration was measured and the associated triggered calcium transient was analysed using the calcium-sensitive fluorescent indicator Fura-2AM.Heart failure was associated with in vivo evidence of autonomic dysfunction, including a 38 % increase in the resting heart rate, blunting of the heart rate response to dobutamine, and almost complete loss of vagal tonic heart rate control. This pattern was not present in dyssynchrony. At a cellular level, normal sheep had heterogeneity of action potential duration, which was longer in the septum than the free wall. Heart failure disrupted this pattern, and was also associated with approximately a 40 % reduction in the magnitude of the calcium transient in both the septum and the free wall. Dyssynchrony was associated with a similar reduction in the calcium transient, but this was isolated to the free wall.RV apical pacing therefore induced a phenotype that resembled a localised cardiomyopathy, but without the associated autonomic dysfunction of the heart failure model. However, it was possible to identify a subgroup within these subjects that displayed a pattern of autonomic changes similar to those seen in heart failure, and this appeared to be associated with the most profound cellular changes. This raises the possibility that early dyssynchrony-induced cardiomyopathy may manifest as changes in the autonomic profile, which may be detectable in clinical practice." @default.
• W2317759260 created "2016-06-24" @default.
• W2317759260 creator A5057200391 @default.
• W2317759260 date "2014-11-03" @default.
• W2317759260 modified "2023-09-28" @default.
• W2317759260 title "A translational approach to dyssynchrony" @default.
• W2317759260 hasPublicationYear "2014" @default.
• W2317759260 type Work @default.
• W2317759260 sameAs 2317759260 @default.
• W2317759260 citedByCount "0" @default.
• W2317759260 crossrefType "dissertation" @default.
• W2317759260 hasAuthorship W2317759260A5057200391 @default.
• W2317759260 hasConcept C126322002 @default.
• W2317759260 hasConcept C164705383 @default.
• W2317759260 hasConcept C2776034619 @default.
• W2317759260 hasConcept C2776720267 @default.
• W2317759260 hasConcept C2777953023 @default.
• W2317759260 hasConcept C2778198053 @default.
• W2317759260 hasConcept C2778921608 @default.
• W2317759260 hasConcept C2780074459 @default.
• W2317759260 hasConcept C71924100 @default.
• W2317759260 hasConcept C78085059 @default.
• W2317759260 hasConcept C84393581 @default.
• W2317759260 hasConceptScore W2317759260C126322002 @default.
• W2317759260 hasConceptScore W2317759260C164705383 @default.
• W2317759260 hasConceptScore W2317759260C2776034619 @default.
• W2317759260 hasConceptScore W2317759260C2776720267 @default.
• W2317759260 hasConceptScore W2317759260C2777953023 @default.
• W2317759260 hasConceptScore W2317759260C2778198053 @default.
• W2317759260 hasConceptScore W2317759260C2778921608 @default.
• W2317759260 hasConceptScore W2317759260C2780074459 @default.
• W2317759260 hasConceptScore W2317759260C71924100 @default.
• W2317759260 hasConceptScore W2317759260C78085059 @default.
• W2317759260 hasConceptScore W2317759260C84393581 @default.
• W2317759260 hasLocation W23177592601 @default.
• W2317759260 hasOpenAccess W2317759260 @default.
• W2317759260 hasPrimaryLocation W23177592601 @default.
• W2317759260 hasRelatedWork W1545583055 @default.
• W2317759260 hasRelatedWork W1556486226 @default.
• W2317759260 hasRelatedWork W162154629 @default.
• W2317759260 hasRelatedWork W1965472568 @default.
• W2317759260 hasRelatedWork W1967312024 @default.
• W2317759260 hasRelatedWork W1993565042 @default.
• W2317759260 hasRelatedWork W2003007322 @default.
• W2317759260 hasRelatedWork W2006428535 @default.
• W2317759260 hasRelatedWork W2022496201 @default.
• W2317759260 hasRelatedWork W2023290191 @default.
• W2317759260 hasRelatedWork W2027806010 @default.
• W2317759260 hasRelatedWork W2043277117 @default.
• W2317759260 hasRelatedWork W2059523482 @default.
• W2317759260 hasRelatedWork W207180069 @default.
• W2317759260 hasRelatedWork W2082077826 @default.
• W2317759260 hasRelatedWork W2128952525 @default.
• W2317759260 hasRelatedWork W2138917189 @default.
• W2317759260 hasRelatedWork W2149321863 @default.
• W2317759260 hasRelatedWork W2416719656 @default.
• W2317759260 hasRelatedWork W821076316 @default.
• W2317759260 isParatext "false" @default.
• W2317759260 isRetracted "false" @default.
• W2317759260 magId "2317759260" @default.
• W2317759260 workType "dissertation" @default.