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52. CARDIAC ALLOGRAFTS FROM DONATION AFTER CIRCULATORY DEATH DONORS – ARE THESE HEARTS VIABLE FOR USE IN CARDIAC TRANSPLANTATION?

Author

Macdonald, Peter, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW, Dhital, Kumud, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW, Iyer, Arjun, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW, Macdonald, Peter, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW, Dhital, Kumud, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW, and Iyer, Arjun, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW

Abstract

Cardiac Transplantation remains the definitive treatment of End-Stage Heart Failure beyond medical therapy, with excellent recipient survival and quality of life. However, its major limitation remains in the finite number of cardiac allografts available for transplantation. Whilst all hearts have previously been procured solely from brain dead donors, the search for additional sources of organs have led investigators to Donation after Circulatory Death (DCD) donors. The body of work enclosed in this thesis investigates the viability of hearts from these DCD donors for use in cardiac transplantation. These hearts have been avoided, having been exposed to varying periods of warm ischaemia - referring to hypoxic and hypoperfusion insults at normothermic conditions. However, there is inherent tolerance to these insults prior to irreversible damage. The initial series of experiments utilised a large animal model to investigate the warm ischaemic time (WIT) limit prior to irrecoverable damage at a biochemical, metabolic & functional level. These studies demonstrated irrecoverable damage beyond 20 minutes WIT. However, utilising post-conditioning strategies aimed at activating cellular protective pathways, tolerance could be increased to 30 minutes. The next series of experiments were aimed at demonstrating clinical relevance. Utilising a large animal orthotopic transplant model, post-conditioned hearts exposed to 30 minutes WIT were transplanted into recipient animals following 4 hours of storage. Storage of the allografts were either through the current standard of care (cold storage) or with ex-vivo perfusion (EVP) preservation (Transmedics OCS). Superiority and viability of cardiac allografts post-transplantation were only demonstrated when preserved with EVP. Based on these results and a series of human pre-clinical studies, the first human DCD cardiac transplant of the modern era was performed in July 2014. The series of the first 3 of these heart transplants was pub

Published
2017

53. Pathophysiological Trends During Withdrawal of Life Support

Author

Iyer, Arjun, primary, Chew, Hong Chee, additional, Gao, Ling, additional, Villanueva, Jeanette, additional, Hicks, Mark, additional, Doyle, Aoife, additional, Kumarasinghe, Gayathri, additional, Jabbour, Andrew, additional, Jansz, Paul Cassius, additional, Feneley, Michael P., additional, Harvey, Richard P., additional, Graham, Robert M., additional, Dhital, Kumud K., additional, and Macdonald, Peter S., additional

Published
2016
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56. Donation after Circulatory Death (DCD) Donors

Author

Iyer, Arjun, primary, Macdonald, Peter, additional, Gao, Ling, additional, Doyle, Aoife, additional, Kumarasinghe, Gayathri, additional, Hicks, Mark, additional, Jansz, Paul, additional, Granger, Emily, additional, Spratt, Phil, additional, and Dhital, Kumud, additional

Published
2016
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58. Primary Graft Failure after Heart Transplantation

Author

Iyer, Arjun, Kumarasinghe, Gayathri, Hicks, Mark, Watson, Alasdair, Gao, Ling, Doyle, Aoife, Keogh, Anne, Kotlyar, Eugene, Hayward, Christopher, Dhital, Kumud, Granger, Emily, Jansz, Paul, Pye, Roger, Spratt, Phillip, and Macdonald, Peter Simon

Subjects
Article Subject
Abstract

Primary graft failure (PGF) is a devastating complication that occurs in the immediate postoperative period following heart transplantation. It manifests as severe ventricular dysfunction of the donor graft and carries significant mortality and morbidity. In the last decade, advances in pharmacological treatment and mechanical circulatory support have improved the outlook for heart transplant recipients who develop this complication. Despite these advances in treatment, PGF is still the leading cause of death in the first 30 days after transplantation. In today's climate of significant organ shortages and growing waiting lists, transplant units worldwide have increasingly utilised “marginal donors” to try and bridge the gap between “supply and demand.” One of the costs of this strategy has been an increased incidence of PGF. As the threat of PGF increases, the challenges of predicting and preventing its occurrence, as well as the identification of more effective treatment modalities, are vital areas of active research and development.

Published
2011
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60. Physiological Correlates of Memory in a Classroom Environment

Author

Nagle, Corinne, primary, Tat, Michael, additional, Frustace, Bruno, additional, Deason, Rebecca, additional, El‐Shaar, Ala'a, additional, Iyer, Arjun, additional, Gherbmichael, Abnet, additional, Wang, Edward, additional, Flannery, Sean, additional, Budson, Andrew, additional, and Zumwalt, Ann, additional

Published
2015
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61. Evaluation of Optimal Proximal Interphalangeal (PIP) Joint Fusion Angle Using Simulated Joint Arthrodesis

Author

Yevheniy Lider, Sisto Sue, Karen DeChello, Iyer Arjun, Mitchell S. Fourman, and Alexander B. Dagum

Subjects
Orthodontics, Fusion, Occupational Therapy, Computer science, Arthrodesis, medicine.medical_treatment, Pip joint, Joint arthrodesis, medicine
Abstract

Date Presented 4/17/2015 In this study, we aim to identify an optimal proximal interphalangeal (PIP) fusion angle that will preserve pinch strength and dexterity as well as maximize performance in daily functional activities. Study results will facilitate better occupational therapy treatment outcomes and occupational performance.

Published
2015
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65. Abstract 20

Author

Lider, Yevheniy, primary, Fourman, Mitchell, additional, DeChello, Karen, additional, Iyer, Arjun, additional, Sisto, Sue, additional, and Dagum, Alexander, additional

Published
2014
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67. Gaze tracking variables as indicators of learning

Author

Iyer, Arjun

Subjects
Neurosciences
Abstract

The process of learning contains multiple aspects, whose intricacies have yet to be fully understood. The current experiment utilized gaze tracking technology to observe whether variables in subjects' gaze (e.g total time spent on a given image, percentage of time spent on cognitively salient features of the image) was predictive of the subject learning the material. Subjects consisted of students from a Medical Gross Anatomy course, who were tested twice-once before they had learned the course and once after they had learned a certain amount of material. Following the baseline testing, subjects were broken up into three groups, A, B and C, each representing a later visit in the course. Results indicated that groups B and C tended to spend more time on cognitively salient areas of interest, but this was moderated by familiarity. Moreover, results indicated that groups B and C tended to spend more time on images overall (end time) compared with group A or the baseline group. Overall, the results obtained were ambiguous, and warrant further study in order to arrive at a clear conclusion. Future directions of study may want to consider other gaze tracking variables, such as the time at which a subject first looks at a cognitively salient area of interest.

Published
2014

68. Australian outcomes from heart transplantation in the machine perfusion era.

Author

Joshi Y, MacLean C, Emmanuel S, Wang K, Soto C, Villanueva J, Gao L, Doyle A, Dutta S, Wu J, Vaidhya N, Granger E, Watson A, Connellan M, Iyer A, Jansz P, and Macdonald P

Abstract

Background: In the current era of heart transplantation, machine perfusion strategies are emerging as potential additions to the armamentarium of a transplant unit. Donation after circulatory death (DCD) donor hearts assessed through normothermic machine perfusion (NMP) has helped expand the donor pool. Hypothermic machine perfusion (HMP) is emerging as an alternative strategy to traditional static cold storage (SCS) when a prolonged ischemic time is anticipated in brain dead (BD) donors, this is important in Australia where long distant procurement is vital. In this study we examine the outcomes in our unit where both forms of machine perfusion (NMP and HMP), as well as SCS is utilized for donor heart preservation, with a particular focus on severe primary graft dysfunction (sPGD) and mortality., Methods: The year 2021 represents the year when both forms of machine perfusion were available to our unit. Heart transplants in our unit from January 2021 to February 2024 were categorized into three groups for retrospective analysis: (I) DCD-NMP group (n=44); (II) BD-HMP group (n=38), and (III) BD-SCS group (n=78)., Results: There were no significant differences in the mean donor and recipient ages between the three groups. Donor preservation time in the BD-HMP group was significantly longer than the donor ischemic time in the BD-SCS group, and organ care system (OCS) run time in the DCD-NMP group (361±89 vs. 208±47 and 249±49 min respectively, P<0.001). For DCD-NMP, BD-HMP and BD-SCS groups respectively: 30-day survival was: 100%, 97% and 100%; 1-year survival was: 94%, 90% and 94%; 2-year survival was: 90%, 90% and 89% (P=0.9). There was no significant difference in the incidence of sPGD between the three groups (DCD-NMP: 7%, BD-HMP: 5%, and BD-SCS: 5%, P=0.9)., Conclusions: Machine perfusion strategies represent important additions to the modern transplant unit and can expand the donor pool. Results are encouraging with no differences in 2-year survival or incidence of sPGD across the preservation modalities: DCD-NMP, BD-HMP, and BD-SCS., Competing Interests: Conflicts of Interest: Y.J. is supported by a National Heart Foundation PhD scholarship. P.M.: modules in kind from XVIVO and Transmedics (unrelated to submitted work); Novartis and Amgen (grant paid to institution), Novartis, Boehringer-Ingelheim and Astra-Zeneca (Advisory board membership). The other authors have no conflicts of interest., (2024 AME Publishing Company. All rights reserved.)

Published
2024
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