Prof. Yugeesh Lankadeva

Florey Institute of Neuroscience and Mental Health, Melbourne, Australia

For over a decade, Oxford Optronix has been a proud supporter of the translational research at the Florey Institute of Neuroscience and Mental Health (The Florey) in Australia, particularly the ground breaking work conducted by Prof. Yugeesh Lankadeva and colleagues. Prof. Lankadeva is a National Health and Medical Research Council Emerging Leader (Level 2) and a National Heart Foundation Future Leader (Level 2) Fellow, Theme Head of Systems Neuroscience and leads the Translational Cardiovascular and Renal Research Group at The Florey. His research focus lies in investigating the pathophysiology of brain and kidney injury caused by sepsis, heart surgery and heart failure. The goal being to develop innovative diagnostics and therapeutics to improve patient outcomes.

Prof. Lankadeva's discoveries have had significant clinical relevance, resulting in over 70 publications and more than $18 million raised in research funding. His ground breaking work has translated into 10 clinical trials spanning multiple countries. Additionally, he holds three patents and has received over 20 prestigious career awards from organizations including the National Heart Foundation of Australia, Australian Institute of Policy and Science, Hypertension Australia, World Congress for Microcirculation, Microcirculation Society, and Harold Mitchell/CAS/Miller/Jack Brockhoff Foundations.

Prof. Lankadeva’s research focus

The Translational Cardiovascular and Renal Research Group, under Prof. Lankadeva's leadership, addresses critical health complications affecting millions globally. Through the development of pioneering large animal models co-designed with practicing clinical specialists, the group aims to continuously assess brain, heart, and kidney health before, during and after sepsis, heart surgery, and heart failure. Their research provides the scientific rationale for the conceptual design of new clinical trials to improve brain, heart, and kidney health outcomes associated with these life-threatening pathophysiological conditions.

Prof. Lankadeva’s research involving clinically relevant sheep models have revealed that reduced microcirculatory blood flow and oxygen in the inner region of the kidneys (renal medulla) is a common pathophysiological feature of sepsis and heart surgery-associated acute kidney injury. His research aims to identify clinically feasible biomarkers and therapies to prevent and/or reverse renal medullary hypoxia and acute kidney injury in operating theatres and intensive care units.

How the team utilizes the OxyLite and OxyFlo devices

Prof. Lankadeva has made significant contributions to the fields of perioperative medicine, intensive care medicine and nephrology, supported through utilization of the OxyLite and OxyFlo systems by Oxford Optronix. These technologies have provided valuable real-time insights into the pathophysiology of acute brain and kidney injury, renal and cerebral oxygenation, and the effects of therapies on brain and kidney health.

OxyLite Pro and OxyFlo Pro in a stack configuration

The OxyLite has played a pivotal role in shedding light on the oxygenation status of different regions of the brain and kidneys. By continuously monitoring cerebral cortical, renal cortical and medullary tissue oxygenation levels in real-time, Prof. Lankadeva and his team have gained invaluable insights into cerebral and renal physiology and pathophysiology. His findings have not only enhanced our understanding of acute brain and kidney injury but also hold potential implications for the development of targeted diagnostics and interventions to improve patient outcomes.

The OxyLite has helped explore the impact of clinical therapies for sepsis on intra-renal oxygenation, including fluids, diuretics, sedatives, and vasopressors. This trailblazing research has significantly advanced our understanding of the complex regulation of renal oxygenation and informed patient management strategies in operating theatres and intensive care units.

In addition to the OxyLite, Prof. Lankadeva also utilizes the OxyFlo system in his research. This complementary device provides a readout of blood flow dynamics in the brain and kidney microcirculation. By employing unique, combined parameter sensors, Prof. Lankadeva’s team have been able to gain a comprehensive understanding of both blood flow and oxygen status in two vital organs simultaneously, enabling a more holistic understanding of the pathophysiology and the safety and efficacy profiles of new interventions.

In clinical research involving the OxyLite system, Prof. Lankadeva and his team have explored novel mechanism-guided interventions to help prevent acute kidney injury. By closely monitoring urinary oxygen levels, valuable insights have been gained into renal medullary oxygenation, which correlates with overall kidney health. This pioneering research holds promise in guiding physicians to develop strategies that may mitigate the adverse effects of acute kidney injury in patients in the future.

Prof. Yugeesh Lankadeva and Prof. Clive May in theatre

Key articles citing OxyLite and OxyFlo

Hu R., et al. (2022) - Critical Care
Continuous bladder urinary oxygen tension as a new tool to monitor medullary oxygenation in the critically ill

This perspective explores the use of continuous bladder urinary oxygen tension as a novel method to monitor medullary oxygenation in critically ill patients in operating theatres and intensive care units.

The paper highlights the potential of using an optical oxygen sensor (the OxyLite) to measure bladder urinary oxygenation in both animal and human studies in sepsis and heart surgery. The OxyLite offers advantages over traditional polarographic oxygen sensing techniques and provides valuable insights into the adequacy of renal medullary oxygenation.

Nobuki O., et al. (2020) – Am J Physiol Regul Integr Comp Physiol
Rapid and persistent decrease in brain tissue oxygenation in ovine gram-negative sepsis

This study validated the surgical technique for continuously monitoring cerebral tissue perfusion, oxygenation, and temperature over 24-hours of Gram-negative sepsis in sheep, which has now been extended to heart surgery. The study found that sepsis-induced brain injury was associated with an early onset of progressive reductions in cerebral oxygenation in the frontal cortex over 24 hours of live infection.

The study employed the OxyLite and OxyFlo devices to measure cerebral tissue perfusion, oxygenation and temperature within the front cortex simultaneously via a single, combined sensor at each location.

Lankadeva Y., et al. (2021) – Critical Care Medicine
Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C

This study investigates the safety and efficacy of megadose sodium ascorbate in treating sepsis. The study found that intravenous megadose sodium ascorbate was able to reverse renal medullary tissue ischemia and hypoxia, and acute kidney injury in sheep with Gram-negative sepsis without adverse side effects. The OxyLite and OxyFlo systems were again used to provide kidney pO2 and kidney perfusion readouts.

The discovery provided the scientific rationale to treat a patient at Austin Hospital with COVID-19 induced septic acute kidney injury, who was unresponsive to standard care treatments. The sodium ascorbate megadose treatment rescued this critically patient from intensive care, leading to hospital discharge. Together, the observations informed the conceptual design of a Phase Ia randomised controlled trial in 30 patients with septic shock at the Austin Hospital [ACTRN12620000651987p], which demonstrated that megadose sodium ascorbate was safe and that it improved kidney function, reduced the need for blood pressure maintaining drugs and reduced multi-organ dysfunction in septic patients.

Prof. Lankadeva has received a $AUD 4.9 million Australian federal government grant to advance this promising therapy to Phase Ib and Phase II multi-centre clinical trials across all of mainland Australia from 2023-2028 [MRF2022388].

Lankadeva Y., et al. (2018) – Critical Care Medicine
Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation During Angiotensin II Therapy in Septic Acute Kidney Injury

This study employs the OxyLite and OxyFlo devices to measure renal perfusion and pO2, and bladder urinary pO2 during development of septic acute kidney injury in sheep. The study finds bladder urinary pO2 to be a reliable surrogate for renal medullary hypoxia and capable of predicting the risk of acute kidney injury up to 24 hours earlier than conventional clinical diagnostics.

Lankadeva Y., et al. (2019) – Kidney International
Strategies that improve renal medullary oxygenation during experimental cardiopulmonary bypass may mitigate postoperative acute kidney injury

Investigates the use of the OxyLite and OxyFlo devices by Oxford Optronix to measure renal cortical and medullary microcirculatory perfusion and pO2 before and during heart surgery requiring cardiopulmonary bypass. The study found that currently employed clinical perfusion conditions for cardiopulmonary were inadequate to protect the kidneys from developing renal medullary tissue ischemia and hypoxia, which is a hallmark of acute kidney injury. This study also found that renal medullary ischemia and hypoxia during cardiopulmonary bypass can be reversed by increasing target pump flow and blood pressure, which informed the conceptual design of a clinical trial testing this novel intervention in patients undergoing heart surgery to reduce post-operative acute kidney injury [ACTRN12619000128190].

In summary

Prof. Yugeesh Lankadeva's research has significantly contributed to our understanding of acute brain and kidney injury, and provided a strong rationale to develop treatments that are safe for preserving the cerebral and renal microcirculation in the setting of sepsis and heart surgery. These discoveries have rapidly translated to multiple mechanism-guided clinical trials across North America, Europe, Asia, and Australia and have the potential to advance the field of perioperative medicine, intensive care medicine and nephrology, and to improve patient outcomes.

Through their world-renowned expertise, research funding success, and knowledge exchange efforts, Prof. Lankadeva and his team continue to make remarkable advances in the field of cardiovascular, cerebrovascular, and renal research, benefiting both the scientific community and patient care on a global scale.

The team

The Florey team
The extended clinical team comprising the Pre-Clinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia. Image provided by The Florey.