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Current Research Projects

Cardioprotective Approaches in Pulmonary Arterial Hypertension

Gerald J. Maarman  (3rd year PhD student)

Supervisor: Assoc Prof. Sandrine Lecour ; Co-supervisor/s: Prof. Karen Sliwa

Year projected started: 2011

Projected year of completion: 2014

Overview of study:

Pulmonary arterial hypertension (PAH) is a devastating disorder that affects patients with diseases such as chronic obstructive pulmonary disease, schistosomiasis, systemic sclerosis and HIV/AIDS. The pathophysiology of PAH is not completely understood and this is the main reason why current PAH treatments have limited impact on patient survival and quality of life. Therefore, PAH remains a deadly disorder and constant research is being done to develop new and better treatments. My PhD project investigates novel treatments that can protect the heart against PAH-induced damage. One such treatment is a pharmacological agent called melatonin, which has been shown to be cardioprotective in hypertensive and ischemic heart disease. We aim to test whether melatonin can be cardioprotective in PAH. This project may prove melatonin to be a cheap and effective treatment against PAH.

Outcomes:

Review paper: That comprehensively reviews the role of animal models in PAH

Review paper: That highlights novel cardioprotective approaches to protect the right ventricle in PAH

Progress made in the project thus far:

  1. I established an experimental model of monocrotaline-induced PAH in our lab
  2. I characterised the model by assessing cardiac, hemodynamic, biometric and immunohistochemical parameters
  3. I performed a dose response test to establish the most efficacious dose of melatonin in order to achieve cardioprotection against PAH
  4. I administered chronic melatonin treatment by giving melatonin at various time points ascertaining the most effective intervention time
  5. I visited two different working groups (laboratories) in Germany as part of my PhD training to learn an experimental model of right ventricular hypertrophy
  6. Obtained blood samples from patients with PAH for assessment of various parameters to serve as a link between basic science research and clinical scenarios

 Techniques used/to be used in this project:

  1. ORAC assay – To measure total antioxidant activity in blood plasma collected from experimental animals with PAH
  2. Catalase and superoxide dismutase assay – To measure antioxidant enzyme activities of heart and lung tissue as well as plasma samples
  3. TBARS assay – To measure lipid peroxidation in blood plasma collected from experimental animals with PAH
  4. Isolated rat heart perfusion system: To measure ex vivo cardiac function
  5. Echocardiography: To measure in vivo cardiac function & pulmonary pressures
  6. Western blot analysis: To assess cardiac signalling pathways possibly involved
  7. Histology: To assess pulmonary artery mascularisation, fibrosis and cardiomyocyte size, pulmonary artery medial thickening
  8. Oxygraph: To assess possible effects on cardiac mitochondrial respiration