| Artery stenting and angioplasty | Pig coronary stenting/balloon angioplasty model We can deliver drugs either from the stent (drug-eluting stents) or via local delivery from a suitable catheter. Rabbit iliac/subclavian stenting As with the pig, one advantage is that you can use hyperlipideamic rabbits Mouse wire denudation We can introduce a guidewire into the carotid and denude the brachiocephalic artery and aorta to study neointimal formation with obvious applications in genetically modified mice. Mouse vein grafting We can graft a vena cava from a donor mouse interposed into a mouse carotid in the recipient. This leads to arterialisation of the vein and models vein graft failure in humans. | Andy Baker Robert McDonald Simon Kennedy Rodger Wadsworth Pasquale Maffia |
| | Rat Balloon Angioplasty | Pasquale Maffia |
| Cardiovascular mouse and rat strains | Stroke-prone spontaneously hypertensive rat (SHRSP) and its normotensive reference strain, the Wistar Kyoto rat (WKY). The SHRSP is a genetic model of human essential hypertension, cardiac hypertrophy and stroke. It is currently being used in genetic studies, pharmacological interventions and gene transfer studies. Congenic and consomic strains derived from SHRSP and WKY crosses, designer strains used to identify candidate genes for hypertension and salt-sensitivity. | Anna Dominiczak Delyth Graham |
| | ApoE-/- knockout mouse When fed a high-fat diet, this model develops unstable atherosclerotic lesions in the brachiocephalic artery. Surgical/pharmacological modifications to the model include, periarterial cuff placement, wire injury of major artery(s), myocardial infarction, thioglycoage administration. | Andy Baker Robert McDonald |
| | Angiotension II-induced hypertension and cardiac remodelling (left ventricular hypertrophy and fibrosis) in mice | Stuart Nicklin |
| | Kit w-sh/w-sh | Roger Wadsworth Catherine Lawrence |
| | MKP-2 deletion (DUSP-4) PAR-2 deletion | Robin Plevin |
| Cardiac Rhythm | Antiarrhythmic drugs, cardiovascular safety pharmacology | Susan Coker |
| Heart Failure | Mouse cardiac hypertrophy; altered calcium signalling in heart failure; ryanodine receptor function in normal and failing hearts; calcium/calmodulin dependent protein kinase II in cardiac function | Susan Currie |
| Hypertension | Idendification of candidate genes for hypertension and salt-sensitivity; haemodynamic measurement by radiotelemetry or tail-cuff plethysmography; assessment of cardiac function and hypertrophy by echocardiography and pulse wave Doppler; metabolic cages for assessment of renal function; gene transfer studies using adenoviruses, lentiviruses or adeno-associated virus | Anna Dominiczak Delyth Graham Andy Baker Lorraine Work |
| Kidney disease | Anti-Thy1.1 rat model of glomerulonephritis Glomerulonephritis is induced by intravenous injection of the mouse monoclonal IgG antibody ER4 anti-rat Thy1.1. The model is currently used in gene transfer and pharmacological intervention studies. Unilateral ureter obstruction model of kidney fibrosis | Andy Baker Alan Jardine Laura Denby |
| Metabolic disorders | Fructose fed SHRSP, a model of metabolic syndrome After 60% fructose diet for two weeks the SHRSP demonstrates glucose intolerance, dyslipidaemia, increased adiposity index and hypertension. | Delyth Graham |
| Myocardial infarction | Rabbit and rat models of myocardial infarction (MI) with echocardiographic assessment The MI is induced by ligation of a descending brance of the left coronary artery. This creates a transmural infarct and commensurate cardiac hypertrophy and electrical remodelling. Mouse model of myocardial infarction We are in the process of producing mice with an MI caused by ligation of a coronary artery. We have the capability to characterise this model both in vivo and ex vivo. Enabling technologies Pressure volume measurements for cardiac function (Rodents) in vivo and ex vivo on working heart system (Rabbit) These represent state-of-the-art measurements for assessing diastolic and systolic intraventricular pressure in laboratory animal hearts. They are now the gold standard for assessing cardiac function. ECG measurements (Rodents) in vivo and ex vivo on Langendorff/working heart systems (Rodents and Rabbits) Mouse and rat exercise model using treadmill These measurements involve VO2 MAX measurements on rodents alsong with exercise performance. The regimen is very similar to interval training systems used in humans. Characterisation of host-parasite interactions (in particular parasite-cardiomyocyte interactions) We have recently set up collaborations with the Wellcome centre for Molecular Parasitology to assess direct interactions between parasites and the heart. Simple and more complex assay systems have been developed for this purpose. Monophasic action potential measurements and wide filed optical measurements of epicardial and transmural electrical activity in vitro Standard MAP electrode recordings (can be used in vivo) along with the use of novel optical sensors to image electrical activity (currently in vitro only). Pharmacological/physiological drug characterisation using in vitro preparations including single cell isolation. Electrophysiology & fluorescence imaging techniques We have extensive experience in the use of these techniques to examine the effects of drugs on the cellular electrophysiology of atrial and ventricular myocytes. We have also experience with isolated atria/sino-atrial node and atrioventricular node preparations. | Godfrey Smith Christopher Loughrey Ole Kemi Tony Workman Susan Currie |
| Pulmonary hypertension | Hypoxic rat model Unique transgenic models (over-expressing serotonin transporter, s100A4/mts1, BMPR2+/- deficient in tryptophan hydroxylase1 and peripheral serotonin) Monocrotaline rat Secondary to Systemic Lupus Erthrematosus (SLE) (MRL/lpr mice) Haemodynamics and pathology | Mandy MacLean Roger Wadsworth Margaret Harnett |
| | Serotonin and serotonin transporters in pulmonary hypertension; transgenic models over-expressing serotinin transporter, s100A4/mts1, BMPR2+/- deficient in tryptophan hydroxylase1 and peripheral serotonin | Mandy MacLean |
| | Monocrotaline rat secondary to systemic lupus erythrematosus (SLE) (MRL/lpr mice) | Mandy MacLean Margaret Harnett |
| Stroke | Middle cerebral artery occlusion (MCAO) models of stroke sensitivity in the SHRSP including both permanent and ischemia/reperfusion models. After MCAO, MRI imaging of the brain is used to assess infarct volume, investigate ischaemic penumbra and characterise changes in cerebral blood flow. Behavioural testing of sensorimotor function may also be assessed after MCAO. | Lorraine Work |
| Vein graft remodelling | Mouse interpositional vein graft; immune cell function and cell signalling in vein graft remodelling | Simon Kennedy Roger Wadsworth |
| | Rabbit vein-artery fistula; vascular tissue remodelling, growth and phenotype changes in the remodelled vascular wall | Paul Coats Roger Wadsworth |
