Arrhythmogenesis in Pulmonary Hypertension

  • Ian Temple

Student thesis: Phd


Background: Pulmonary arterial hypertension (PAH) is a condition with severe morbidity and mortality. It is associated with an increase in incidence of all forms of arrhythmias which further increase morbidity and mortality. The monocrotaline (MCT) model of pulmonary hypertension (PH) in the rat is analogous to PAH in humans and was used to study how PH causes arrhythmias.Methods: A single injection of MCT or a volume matched saline injection (control) was given to the rats on day 0 of the protocol. The hearts of both groups of rats were studied in vivo with echocardiography (echo) and electrocardiogram (ECG). The rat's condition was monitored and they were electively sacrificed when they showed symptoms or on day 28. Live cardiac tissue was studied using the Langendorff preparation and a right atrial preparation that incorporated the sinoatrial (SA) and atrioventricular (AV) nodes. Molecular biology techniques including reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were used identify changes in the heart caused by PH. The effects of macitentan, an endothelin receptor antagonist used in the treatment of PAH, on the MCT injected rats was assessed using echo and ECGResults: Echo demonstrated that the MCT treated rats developed severe pulmonary hypertension with a decreased pulmonary artery acceleration time (P
Date of Award31 Dec 2014
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorMark Boyett (Supervisor)


  • atrioventricular node
  • ion channel

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