Dispersion of repolarisation and refractoriness induced by amiodarone, d-sotalol, myocardial ischaemia and hypertrophy
Başlık:
Dispersion of repolarisation and refractoriness induced by amiodarone, d-sotalol, myocardial ischaemia and hypertrophy
Yazar:
Sneddon, Kenneth Paxton, author.
ISBN:
9780438059276
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (333 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: Martin Hicks.
Özet:
Class III antiarrhythmic drugs prolong repolarisation and have been the subject of recent clinical trials attempting to reduce the incidence of sudden cardiac death in high-risk patients. Pure class III agents, such as d-sotalol have not reduced the risk of arrhythmias in these clinical trials whereas amiodarone, a class III agent with many other properties, has shown considerable promise. It is hypothesised that during regional ischaemia the class III effects of these drugs are attenuated which may lead to increased electrical dispersion in the heart. However amiodarone may still be beneficial against arrhythmias due to its wide range of electrophysiological properties whereas d-sotalol will lose any antiarrhythmic efficacy. In addition, the "pure" class III agent may actually cause an increase in electrical dispersion and arrhythmogenesis upon the regional loss of its class III activity. Again, amiodarone may not have such a potentially harmful effect due to its additional electrophysiological properties. The presence of left ventricular hypertrophy will further complicate matters in two main ways. Firstly, if hypertrophied muscle becomes ischaemic, the rate of shortening of action potential duration is more rapid than in non-hypertrophied muscle, which may amplify any electrical dispersion (Hicks et al., 1995). Secondly, LVH may be involved in more complex interactions to modify the effects of class III agents in association with regional ischaemia. Therefore, this study aimed to investigate the relationship between electrical dispersion and arrhythmogenesis during acute regional ischaemia in normal and hypertrophied hearts. The effects of ischaemia and left ventricular hypertrophy on the electrophysiological actions of amiodarone and d-sotalol were also studied in normal and hypertrophied hearts. A model of acute regional ischaemia in an isolated working rabbit heart was characterised. Electrophysiological parameters were measured at 3 epicardial sites (right ventricle and apical and basal left ventricle) or at 2 epicardial and 1 endocardial sites in the left ventricle. The parameters recorded were monophasic action potential duration to 90% repolarisation (MAPD90), effective refractory period (ERP) and conduction delay. These were used to calculate dispersion of MAPD90 and repolarisation (corrected for conduction delay) and dispersion of ERP and refractoriness (corrected for conduction delay). Haemodynamic parameters (mean forward flow, left ventricular systolic and end-diastolic pressures) were also measured. In this study, ischaemia increased conduction delay, shortened MAPD90 and ERP and increased dispersion of repolarisation and refractoriness between the ischaemic and non-ischaemic areas of the heart. 10-4 M concentrations of d-sotalol and amiodarone prolonged both MAPD90 and ERP under baseline conditions. During ischaemia, upon loss of its class III actions, d-sotalol but not amiodarone elevated ischaemia-induced dispersion of repolarisation. However, ischaemia-induced dispersion of refractoriness was not affected by either drug. Despite the increased dispersion of repolarisation, d-sotalol did not affect the susceptibility to arrhythmias during ischaemia or reperfusion. The epicardium was more sensitive than the endocardium to the effects of ischaemia with regard to MAPD90, ERP and conduction slowing. Left ventricular hypertrophy prolonged MAPD90 and ERP in the left ventricular epicardium, but not the endocardium. Hypertrophy did not alter the differential sensitivity of the epi- and endocardium to ischaemia. Hypertrophy increased the ischaemia-induced transepicardial (but not transmural) dispersion of repolarisation, but not refractoriness. However hypertrophy did not affect arrhythmogenesis during ischaemia and reperfusion. In hypertrophied hearts, d-sotalol increased the ischaemia-induced transepicardial and transmural dispersion of repolarisation, but not refractoriness compared to non-hypertrophied hearts treated with the drug. The drug did not affect arrhythmogenesis during ischaemia. In conclusion, a working heart model has been successfully characterised and can be used to study the electrophysiological and haemodynamic effects of various interventions such as antiarrhythmic drugs during ischaemia and reperfusion in the absence or presence of left ventricular hypertrophy.
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684704.1) | 684704-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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