Cardio 8 Flashcards
How many deaths did CVD cause in 2012 and how many of these were due to ischemic heart disease?
- 5 million
7. 4 million
How many deaths due to CVD in Aus in 2013, and how many due to ischemic heart disease?
43,603 deaths due to heart disease in 2013, with 20,000 of these due to ischemic heart disease
What are the surgical treatments for ischemic heart disease?
- Percutaneous coronary intervention – angioplasty and stenting
- Coronary artery bypass grafting
What are the pharmacological treatments for ischemic heart disease?
- Anti-thrombotic
- Beta adrenergic antagonists (lower BP)
- Calcium channel blockers
- Nitrates (if suffering from angina)
- ACE inhibitors
- Statins (lower cholesterol)
What are embryonic stem cells?
Derived from preimplantation embryo (blastocyst), first human line by Thomson in 1998, allogenic transplantation (cannot use own stem cells, must be derived from another source), pluripotent
What are induced pluripotent stem cells?
Reprogrammed from somatic cells with pluripotent transcription factors, discovered by Takahashi in 2006, autologous transplantation
What are the pros and cons of pluripotent stem cells?
Pros: unlimited proliferative potential, high cardiogenic potential
Cons: risk of tumour formation, risk of arrhythmia
What are the pros and cons of adult stem cells?
Pros: multipotent (low risk of tumour formation), autologous, low immunologic potential, readily available
Cons: limited proliferative potential, low cardiogenic potential, risk of arrhythmia
What adult stem cell is most commonly used for treatment?
Bone marrow
What are the first generation stem cells?
Skeletal myoblasts, bone marrow derived and adipose derived
What are the features of skeletal myoblasts?
Undifferentiated cells residing in the muscular tissue, first cell type tested in patients, differentiated cells are unable to electrically couple with host cardiomyocytes (arrhythmia)
What are the features of bone marrow derived SC?
Unfractioned mononuclear cells, mesenchymal cells or CD34 cells, provided modest improvement in cardiac function
What are the features of adipose derived mesenchymal stem cells?
Multipotent stem cells from fat tissue, easily obtained via liposuction aspirates, safe and feasible
What are the next generation stem cells?
Cardiac Resident Stem Cells, cardiopoietic stem cells
What are the features of cardiac resident stem cells?
Isolated from heart tissue, organ specific stem cells to treat organ specific disease, only c-Kit and cardiosphere cells have been trialled and shown promising results
What are the features of W9B2+?
Found in cell surface membrane, ability to turn into heart cells (cardiomyocyte) and can show AP when stimulated with current. Can also turn into blood vessels, osteocytes (bone), chondrocytes (Cartilage) and adipocytes. Can differentiate into a select group of structures (need specific drug cocktail to determine what structure they turn into - not spontaneous
What are the features of cardiopoietic stem cells?
Not naturally isolated from stem cell - can be invasive to isolate stem cells direct from the heart, take advantage of more readily available stem cell (bone marrow) and treat them with factors to turn them into cardiac stem cells for transplant
What happens during inflammation after an ischemic insult?
- Inflammation
- Cardiomyocyte death
- Immune cell infiltration - ECM breakdown
- Heart may rupture
- 1 week
What happens during proliferation after an ischemic insult?
- Fibroblasts - form scar tissue
- Growth factors are secreted and cause angiogenesis
- 1-2 weeks
What happens during remodelling after an ischemic insult?
- Scar (limited heart cells)
- Weak wall
- Heart cells hypertrophy to compensate for loss of contraction
What is the mechanism of action of cell therapy?
- Secrete growth factors for angiogenesis (increase reperfusion) and compensation for cell death
- Remodel scar tissue and reduce fibrosis
- Activate resonant stem cells in the heart (more heart cells or more growth factors)
What are the challenges with cell therapy?
- No ideal cell source – no perfect stem cell
- Young, healthy patients are ideal candidates for stem cell donation
- Purification of cells is required to minimise risk of cancer formation
- Choice of admin affects safety, how well the stem cells remain and distribute in the target tissue
