Professor Ivan Sammut’s Cardio-Renal Research Group

Research overview

The existence of multi-organ interactions in the development and progression of organ failure is a now universally accepted concept. Innovative treatment strategies are required to improve health outcomes in patients with conditions such as diabetes, heart disease and renal injury. My research group is specifically interested in studying cardio-renal interactions in health and disease. This work has naturally led to new studies on neurohormonal aspects in multi organ disease such as diabetic nephropathy and cardiomyopathies. The objectives of these integrated studies are to understand how normal physiology is altered in different disease states and to develop treatments using both existing and novel pharmacological and surgical interventions.

We employ several techniques to accomplish our research goals, including: telemeterised whole animal models, isolated organ (kidney and heart) haemodynamic studies and in vitro cell toxicity models. This work is conducted in association with imaging and molecular techniques.

We are also engaged in a collaborative programme with chemists at the University of Otago on two funded studies to develop novel therapeutic agents for use in organ protection with valuable clinical benefits. Spin-off studies from this research have also delivered new toxicological agents for industrial applications.

Principal Investigators

Professor Ivan Sammut

Pharmacological and Surgical Intervention in cardio-, renal- and neuronal injury in Cardio-Renal Disease.
We are currently examining the effects of renal denervation on diabetic pathology. This study conducted by Mr Yimin Yao in our group in collaboration with Dr Ged Davis, Dr Joanne Harrison and Prof Rob Walker has shown clear interventional benefit to renal denervation. We are subsequently looking at the autonomic nervous system involvement in this renal pathology.

A second study conducted in collaboration with Associate Professor Steve Kerr examines the development of cardiomyopathy in status epilepticus patients. This is a common neurological emergency associated with a high mortality rate. Previous studies have shown impaired autonomic regulation and seizure-induced cardiomyopathy can occur during epileptic discharge. Our study examines the development of cardiac morphological with ECG and EEG changes in a model of status epilepticus (Vranyac-Tramoundanas et al., 2008 and 2011) and investigates the therapeutic value of sympatholytic agents on this pathology.

Dr Joanne Harrison

Examination of the pharmacological and toxicological effects of carbon monoxide and carbon monoxide donors on renal tissue. We have shown that while carbon monoxide donors can mimic the therapeutic effects of carbon monoxide gas, the metal based carbonyl compounds may produce adverse effects resulting in cell death (Winburn et al., 2012).

Other studies actively conducted within the Cardio-Renal group with Associate Professor I Sammut include the development of seizure-induced cardiomyopathy characterization and the renal injury studies in diabetes.
My research interests and expertise are in the fields of toxicology, inflammation and apoptosis particularly in the context of ischaemia reperfusion injury.

Current research expertise includes:

• Protective and toxic effects of carbon monoxide.
• Biochemical analysis of apoptotic, fibrotic, stress and inflammatory markers in acute tubular necrosis, chronic renal and heart failure.
• Immunolocalisation (using TEM) of molecular markers of apoptosis in ischaemia reperfusion injury.

Current students

• Catherine Leader - PhD Student
• Adam Chau - MSc Student
• Ingrid Fomison-Nurse - MSc Student
• Stephanie Thwaite - MSc Student

Former Students

PhD

• Morgayn Read (2015)
  • Seizure-induced cardiomyopathy: Benefit of Atenolol
• Yimin Yao (2012)
  • Chronic Bilateral Renal Denervation in Experimental Diabetic Nephropathy
• Shiva Nair (2011)
  • The mechanisms of neuroprotection by melatonin in cerebral ischaemia reperfusion
• Ian Winburn (2011)
  • Carbon Monoxide and Hypothermic Pulsatile Perfusion in Renal Transplantation

MSc

• Dominic Parry (2015)
  • Low Dose Inhaled Carbon Monoxide and Cardiac Ischaemia Reperfusion Injury
• Dominic McCann (2015)
  • Comparison of Cardioprotective Therapy with Atenolol and Diltiazem in Seizure-Induced Cardiomyopathy
• Rebecca Millen (2015)
  • Pharmacological Intervention with Atenolol and Diazepam in Seizure-Induced Cardiomyopathy
• Anastasia Andreianova (2015)
  • Therapeutic Approaches in the Attenuation of Seizure-Induced Cardiomyopathy
• Morgayn Read (2012)
  • Cardiac Injury during Kainic Acid Induced Seizures: Effects of Gender on ECG
• Jessica Kelly (2011)
  • Examination of the Hypothalamic Paraventricular Nucleus in a Rat Model of Chronic Ischaemic Myocardial Injury
• Scott Smart (2011)
  • Evidence of Renal Dysfunction, and Sclerotic Damage Secondary to Chronic Heart Failure; an Inbred Rat Model of Type 2 Cardiorenal Syndrome

BSc(Hons), BMedSc (Hons) and BBiomedSc(Hons)

• James Strickland (2016)
  • Comparison of Spironolactone versus Amlodipine in Hypertensive Cardiorenal Pathology
• Alexander Embury (2014)
  • Adrenergic stimulation of HK-2 proximal tubular cells in hyperglycaemic conditions
• Laurence Holding (2012)

  • Hypothalamic changes in Diabetic Nephropathy

Collaborations

University of Otago

• Professor Rob Walker (Dunedin Hospital) with Dr G. Davis: Effectiveness of Renal Denervation in Hyper-Renimec Pathology

• Associate Professor David Larsen (Dept of Chemistry), and Dr Greg Giles (Dept of Pharmacology), Development and pharmacological testing of novel CO releasing molecules

• Associate Professor Steve Kerr (Dept of Pharmacology): Seizure induced cardiomyopathy

National

• Professor C Eason, University of Lincoln and Prof M Brimble, University of Auckland. Toxicity development programme in collaboration with Connovation Research. FRST funded 2009-15.

International

• Associate Professor Paul Chazot, University of Durham, UK, in collaboration with the University of Turin, Italy. Pro-inflammatory histamine receptors in diabetic nephropathy. 2012. This multicentre study is now actively being developed through an EU COST initiative from findings developed across the three centres.