Clive May Laboratory

Laboratory Head

Clive N May BSc (Hons) PhD

Contact Details

Email:

clive.may@florey.edu.au

Phone:

+61 (0)3 8344 7302

Number of

Staff:        6
Students:  2

Research Interests

Neural and endocrine control of the cardiovascular system in health and disease.

Current Projects

Disorders of the brain are commonly associated with diseases such as depression, epilepsy, schizophrenia, and Parkinsonism, but it is important to appreciate that the brain is implicated in a number of cardiovascular diseases. The brain plays a primary role in controlling blood pressure by actions on the heart and blood vessels that are mediated by the autonomic nervous system. We are interested in the control of a branch of this system, the sympathetic nervous system; in particular what causes increased activity of the sympathetic nerves in different diseases.

Mechanisms causing increase sympathetic nerve activity in heart failure

Heart failure is a major public health problem in all Western countries. In addition to the human cost in terms of morbidity and mortality, it has a huge economic cost, estimated to be $1 billion in Australia in 2000. Disturbingly, heart failure is the only cardiovascular disease in which the incidence and prevalence is not decreasing. Despite significant therapeutic advances, morbidity and mortality in heart failure remain unacceptably high.

In HF there is a large increase in the activity of the sympathetic nerves to the heart, which is detrimental in that it causes arrhythmias and sudden death. We are examining what are the messages to the brain and what changes occur in the brain that cause this large increase in cardiac sympathetic nerve activity (CSNA) in heart failure.

We have shown that directly recorded CSNA is dramatically increased in heart failure; there is a 90% chance of there being a burst of nerve activity with each heart beat in heart failure compared with half that in the normal state. We are investigating the mechanisms leading to this increased activity. Studies include investigation of the role of the arterial baroreflexes, cardiopulmonary reflexes, circulating hormones and mechanisms in the brain. In addition, we are simultaneously recording sympathetic nerve activity to the heart, kidney and skeletal muscle to determine whether there are differences in mechanisms controlling these nerves in the normal state and differences in the factors that lead to the increased activity in heart failure.

Acute renal failure in sepsis (in collaboration with Prof Rinaldo Bellomo, Intensive Care Unit, Austin Hospital)

Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%.

There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the last 50 years, except for the use of renal replacement therapy once acute renal failure is established.

The traditional view is that sepsis-induced renal failure results from reduced perfusion of the kidney secondary to the low blood pressure. We demonstrated that in fact the opposite occurs; renal blood vessels dilate and blood flow to the kidney increased.

In collaboration with the Brain Research Institute, we showed that that renal ATP levels, measured by magnetic resonance spectroscopy, were not reduced during sepsis, supporting the suggestion that ischaemia is not an important factor causing acute renal failure. Furthermore, histological studies have not found any tubular injury or apoptosis in septic kidneys, again suggesting that acute renal failure in this setting is unlikely to be due to ischaemic damage.

Present studies are examining the effects of different volume expanders and vasoconstrictor agents to determine the optimum treatments to reduce the level of renal failure in sepsis. In associated studies, the time course and extent of renal and cardiac sympathetic activation in sepsis, and the mechanisms causing this, are being studied.

Treatment of myocardial ischaemia reperfusion injury (in collaboration with A/Prof Owen Woodman, Department of Pharmacology, University of Melbourne)

Coronary heart disease was the leading single cause of death for Australians in 1998, accounting for 22% of all deaths. This problem will become more severe due to the ageing of the Australian population. Moreover, increased survival due to improved acute management of myocardial infarction is leading to an increased prevalence of heart failure, as left ventricular remodelling following a heart attack is the cause of approximately one third of these victims developing heart failure. To prevent the progression of post-infarction left ventricular remodelling to heart failure, it is essential to understand the mechanisms involved and to develop new pharmacological treatments.

Currently, after a heart attack, reperfusion of the blocked coronary artery is the primary aim in order to salvage the damaged myocardium. Unfortunately, reperfusion is associated with a paradoxical worsening of the infarct process, so called “lethal reperfusion injury”, for which there is no treatment.

We have demonstrated that a novel drug, a synthetic compound related to naturally occurring plant products called flavonols, is extremely effective in reducing damage to the heart after a coronary vessel is unblocked. This is accompanied by a reduction in mortality, infarct size and cardiac enzyme release, prevention of the loss of myocardial eNOS, reduced neutrophil infiltration and maintained coronary endothelial function.

Laboratory Techniques

Funding

Project Grants

Other Trusts and Foundations

Additional Information

PubMed link: May CN 

Research