Cardiology
Cardiac benefits by delayed reperfusion after acute myocardial infarction in mice
Supervisors: A/Prof Xiao-Jun Du, Dr Xiao-Ming Gao
Project Site: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, AMREP (Prahran)
Contact: A/Prof XJ Du. T: 85321267; E: xiao-jun.du@bakeridi.edu.au
Project Description: Acute myocardial infarction (AMI) occurs following occlusion of a coronary artery. It is important to re-open the blocked artery to re-establish blood supply to the ischemic myocardium (reperfusion) to save ischemic myocardium from necrosis, i.e. infarct size limitation. Clinically, post-ischemia reperfusion can be achieved most commonly by catheter-based percutaneous primary coronary intervention (PCI) or by thrombolytic drugs. It is usually believed that significant delay (i.e. over 12 hours after onset of ischemic symptoms) in reperfusion does not provide clinical benefits, rather, reperfusion per se may exacerbate further injury to the ischemic heart muscle.
AMI in mice can be induced surgically by coronary artery occlusion. Like human patients, mice with AMI develop cardiac wall rupture, a malignant complication due to post-infarct myocardial inflammation and damage to the extracellular matrix (ECM) architecture of the infarct myocardium. In our recent study on mice, reperfusion was done following 1, 2 or 4 hours after coronary artery occlusion. We observed that the onset of cardiac rupture was completely prevented not only by early, but also by delayed reperfusion (Gao XM, et al: 2012. Due to significantly high metabolic rate in mice, reperfusion following a 4-hour period of ischemia in mice is equivalent to a major delay of reperfusion to humans). This finding clearly indicates benefits achieved by delayed reperfusion. This project is designed to explore the mechanism responsible for such cardiac protection by delayed reperfusion focusing on the extent of inflammation and ECM damage.
The specific aims of this project are:
• To compare delayed reperfusion versus non-reperfusion on the extent of inflammation in the infarct myocardium;
• To determine the extent of ECM damage by biochemical and histological means, between hearts without and with delayed reperfusion;
• To measure the degree of post-infarct ventricular remodelling by non-invasive echocardiography.
Skills: The project will enable the student to gain skills in: understanding the principal of reproducing heart disease models in mice, quantitative histology, biochemical assays, echocardiography in mice, data analysis using a variety of statistical methods.
References
Gao XM, White DA, Liu Y, Dart AM, Du XJ. Post-infarct cardiac rupture: Recent research progress on the pathogenesis and therapeutic interventions. Pharmacol Ther 2012;134(2):156-179.
Cardiac benefits by delayed reperfusion after acute myocardial infarction in mice
Supervisors: A/Prof Xiao-Jun Du, Dr Xiao-Ming Gao
Project Site: Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, AMREP (Prahran)
Contact: A/Prof XJ Du. T: 85321267; E: xiao-jun.du@bakeridi.edu.au
Project Description: Acute myocardial infarction (AMI) occurs following occlusion of a coronary artery. It is important to re-open the blocked artery to re-establish blood supply to the ischemic myocardium (reperfusion) to save ischemic myocardium from necrosis, i.e. infarct size limitation. Clinically, post-ischemia reperfusion can be achieved most commonly by catheter-based percutaneous primary coronary intervention (PCI) or by thrombolytic drugs. It is usually believed that significant delay (i.e. over 12 hours after onset of ischemic symptoms) in reperfusion does not provide clinical benefits, rather, reperfusion per se may exacerbate further injury to the ischemic heart muscle.
AMI in mice can be induced surgically by coronary artery occlusion. Like human patients, mice with AMI develop cardiac wall rupture, a malignant complication due to post-infarct myocardial inflammation and damage to the extracellular matrix (ECM) architecture of the infarct myocardium. In our recent study on mice, reperfusion was done following 1, 2 or 4 hours after coronary artery occlusion. We observed that the onset of cardiac rupture was completely prevented not only by early, but also by delayed reperfusion (Gao XM, et al: 2012. Due to significantly high metabolic rate in mice, reperfusion following a 4-hour period of ischemia in mice is equivalent to a major delay of reperfusion to humans). This finding clearly indicates benefits achieved by delayed reperfusion. This project is designed to explore the mechanism responsible for such cardiac protection by delayed reperfusion focusing on the extent of inflammation and ECM damage.
The specific aims of this project are:
• To compare delayed reperfusion versus non-reperfusion on the extent of inflammation in the infarct myocardium;
• To determine the extent of ECM damage by biochemical and histological means, between hearts without and with delayed reperfusion;
• To measure the degree of post-infarct ventricular remodelling by non-invasive echocardiography.
Skills: The project will enable the student to gain skills in: understanding the principal of reproducing heart disease models in mice, quantitative histology, biochemical assays, echocardiography in mice, data analysis using a variety of statistical methods.
References
Gao XM, White DA, Liu Y, Dart AM, Du XJ. Post-infarct cardiac rupture: Recent research progress on the pathogenesis and therapeutic interventions. Pharmacol Ther 2012;134(2):156-179.
Do the coronary small vessels respond less well to medication in patients with diabetes or renal failure - also offered as MBiomedSc
Supervisors: Professor Judy Savige and A/Prof Deb Colville
Project Site: NWAC, Northern Hospital, Epping.
Contact: ProfessorJudy Savige, T 8344 3260, j.savige@unimelb.edu.au
Project description: Most research into the causes of heart disease has focused on disease in the coronary arteries but the importance of small vessel disease is recognized increasingly. However the coronary small vessels are difficult to study. Nevertheless whenever the small vessels in the heart are affected, small vessels are diseased throughout the body. This includes the vessels in the retina, which are very accessible using a retinal camera and photography. So we propose to examine the retinal small vessels as a model for the coronary arterioles and determine whether renal failure or diabetes means these vessels are diseased and respond less well to medication.
This study involves recruiting patients from the wards with renal failure or diabetes and testing the effect of a tablet that usually dilates small vessels. You will help the patient fill out a questionnaire and also take their blood pressure and retinal photographs, and then review the photographs under the supervision of an ophthalmologist. In addition the retinal photos will be sent to the Centre for Eye Research Australia for the vessel diameters to be measured precisely. The aim of this project is then to determine whether small vessels are less responsive in diabetes and renal failure, and whether medication doses should be increased. The analysis includes univariate and multivariate statistics and backwards linear regression (we will help you with the statistics).
Techniques to be used and skills acquired: This project involves a lot of patient contact, going onto the wards and getting to know hospital staff, learning how to take retinal photographs, and how to interpret abnormalities, as well as statistics.
Feasibility: We already have Human Research Ethics Committee Approval for this project and many of the medical students who have undertaken similar projects during an AMS yyear have achieved a publication from their work.
Natural History of Coronary Plaque Evolutin Through Optical Coherence Tomography - ONLY offered as MBiomedSc
Supervisor/s: A/Prof. Peter Barlis, Dr. Vikas Thondapu; Prof Andrew Ooi, Dr. Eric Poon
Project Site: Department of Mechanical Engineering, Parkville
Contact: Dr Vikas Thondapu E: vthondapu@gmail.com
Project description: Despite groundbreaking advances in cardiology over the past several decades, cardiovascular disease remains the most common cause of death worldwide. The unfortunate reality is that many coronary plaques remain asymptomatic until acute rupture and vessel occlusion, forming a clear impetus for the earlier identification and treatment of high-risk lesions. Intracoronary optical coherence tomography (OCT), a light-based analog of intravascular ultrasound, provides a tenfold improvement in resolution, allowing in vivo imaging of coronary plaques with near-histologic clarity.
This project aims to evaluate the natural history of coronary plaque over 6 months through analysis of angiographic and OCT-derived plaque features. Students will also have the opportunity to engage in state-of-the-art computational fluid dynamic modeling to better understand the role of local micro-hemodynamics in plaque evolution. This work will improve our fundamental understanding of plaque evolution, better define the role of intravascular imaging in the identification of high-risk plaques, and has a potentially high impact in the prospective diagnosis and treatment of coronary artery disease.
Baseline and follow-up angiography and OCT imaging has already been completed in a series of 60 patients. Students will be trained in quantitative coronary angiography and OCT plaque analysis. Those interested in computational modeling will be guided in 3D coronary artery reconstruction and computational fluid dynamic methods.
Evaluation of Coronary Stent Apposition and Intimal Healing Through Optical Coherence Tomography - ONLY offered as MBiomedSc
Supervisor/s: A/Prof. Peter Barlis, Dr. Vikas Thondapu; Prof Andrew Ooi, Dr. Eric Poon
Project Site: Department of Mechanical Engineering, Parkville
Contact: Dr Vikas Thondapu E: vthondapu@gmail.com
Project description: Stent placement is the standard of care in the treatment of occlusive coronary artery disease. The vast majority of patients show improvement and remain asymptomatic after stent placement, however a small but significant subset of patients are prone to adverse long-term complications such as in-stent restenosis and stent thrombosis. The causes of these potentially catastrophic late outcomes remain unclear, but early evidence points to features such as incomplete stent strut apposition and persistently uncovered stent struts. Optical coherence tomography, a high-resolution intravascular imaging technique, offers unprecedented in vivo visualization of individual stent struts and tissue coverage patterns, and is thus an ideal tool to evaluate potential risk factors for late adverse stent complications.
This project aims to compare the stent apposition and late tissue healing characteristics of two commonly used second-generation drug-eluting stents. Students will also have the opportunity to explore the effect of stent malapposition on local micro-haemodynamics through state-of-the-art computational fluid dynamic modeling. Given that over 4 million stents are placed annually around the world, this high-impact project has potentially great clinical significance.
Baseline and follow-up angiography and OCT imaging has already been completed in a series of 60 patients. Students will be trained in quantitative coronary angiography and OCT stent analysis. Those interested in computational modeling will be guided in 3D coronary artery reconstruction and computational fluid dynamic methods.