Professor Peter Macdonald

Professor Peter Macdonald, MD PhD FRACP Laboratory Head, Cardiac Physiology and Transplantation Division  Professor of Medicine, University of New South Wales Telephone: +61-2-8382 2641 Fax: +61-2-8382 3084 Email: pmacdonald@stvincents.com.au

Research Focus:
The major focus of our research group over the last 5 years has been to develop novel methods for preservation of the donor heart in order to improve short-term and long-term outcome of recipients of heart transplants.

We have utilised two models: an isolated working rat heart that permits the rapid and inexpensive evaluation of new treatments, and an orthotopic pig transplant model that incorporates donor brain-death. The latter model is more time-, cost- and labour-intensive, but is critically important as results obtained in this model are directly applicable to clinical practice. The latter model has enabled us to explore treatments that can be administered to the brain-dead donor during the period between declaration of brain death and removal of the donor organs.

Recent studies have focused on the use of combined hormonal therapy to stabilise the donor, and the administration of agents that mimic ischaemic preconditioning or that inhibit the sodium-hydrogen exchange inhibitor.

Currently, we are interested in a number of novel pharmacological approaches to enhancing preservation of the donor heart. These include the use of inhibitors of the enzymes poly(ADP-ribose) synthetase (PARS) and Rho kinase and the use of agents that activate pro-survival/anti-apoptotic signalling pathways within the heart.

1. To develop a management strategy for the brain-dead multiple organ donor that ensures maximal protection and utilisation of all organs that are used for transplantation - including heart, lung, liver, kidney and pancreas.
2. To implement this management strategy of the brain-dead donor at a national level through development of National Guidelines endorsed by all stakeholders.
3. To develop effective preservation strategies that permit viable recovery of hearts and lungs obtained from non-heart beating organ donors.
4. To develop a preservation strategy for heart and lung transplantation that ensures optimal preservation and rapid recovery of function of these organs in the transplanted recipient.
5. To develop alternative novel treatments for end-stage heart and lung disease - eg stem cells, pacing therapies, mechanical and surgical remodelling.
6. To establish a sustainable Higher Degree Program that allows surgical trainees to pursue a higher academic degree (PhD or MD) in the areas of heart failure and transplantation.

Co-Investigators:
Steven Faddy, MSc
Ling Gao, PhD
Mark Hicks, PhD
Paul Jansz, MBBS FRACS PhD
Scott Kesteven, BSc Grad Dip Biomed Eng
Phillip Spratt, MBBS FRACS FRCS

Higher Degree Students:
Alfred Hing, MBBS
Andrew Jabbour, MBBS
Jair Kwan, BSc (Hons)
Alasdair Watson, MBBS

Collaborators:
A/Professor Louise Burrell, Austin Hospital, Melbourne, Australia
Professor Richard Allen, Collaborative Transplantation Research Group; Royal Prince Alfred Hospital, Sydney Australia
Professor Cris dos Remedios, Muscle Research Unit, University of Sydney, Australia
Professor Michael Feneley, MBBS MD FRACP; St Vincent's Hospital, Sydney, Australia
Professor Anne Keogh, MBBS MD FRACP; St Vincent's Hospital, Sydney, Australia
Dr Alexandra Sharland, Collaborative Transplantation Research Group; Royal Prince Alfred Hospital, Sydney Australia

Selected Publications:
Ryan J, Hicks J, Cropper J, Garlick S, Kesteven S, Wilson M, Feneley MP, Macdonald PS. Cariporide (HOE-642) improves cardiac allograft preservation in a porcine model of orthotopic heart transplantation. Transplantation 2003; 75:625-631

Ryan J, Hicks M, Cropper J, Garlick S, Kesteven S, Wilson M, Feneley MP, Macdonald PS. Sodium-hydrogen exchanger inhibition, pharmacological preconditioning or both for extended cardiac allograft preservation. Transplantation 2003; 76:766-771

Gao L, Hicks M, Macdonald PS. Improved preservation of the rat heart with Celsior solution supplemented with cariporide and glyceryl trinitrate. Am J Transplant 2005; 5:1820-1826

Hicks M, Hing A, Gao L, Ryan J, Macdonald PS. Organ preservation. Methods Mol Biol 2006; 333:331-374

Hing A, Hicks M, Garlick S, Gao L, Kesteven S, Faddy SC, Wilson MK, Feneley MP, Macdonald PS. Assessment of the effects of hormone resuscitation on cardiac function and hemodynamics in a porcine model of the brain-dead organ donor. Am J Transplant 2007; 7:809-817

Gao L, Kwan JC, Macdonald PS, Yang L, Preiss T, Hicks M. Improved post-storage cardiac function by poly (ADP-ribose) polymerase: role of phosphatidylinositol 3-kinase Akt pathway. Transplantation 2007; 15:380-386

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