WK 7

• DRUGS = nitrates, beta blockers, calcium channel blockers, K+ channel activator, ranolazine, aspirin/anti-platelet drugs
• Ranolazine blocks excessive prolongation of late inward sodium current in cardiomyocytes --> decrease influx hence depol --> decreases L-type Ca2+ channel influx
• Aspirin irreversibly binds to cox1 --> inhibits prostaglandin synthesis --> inhibits thromboxane synthesis --> unstable embolisms
• captopril is an ace inhibitor
• candesartan is an angiotensin II receptor blocker
• atenolol + bisoprolol are beta-blockers
• GTN, isosorbide dinitrate are nitrates that react to produce NO in vessels to induce vasodilation
• propanolol is a non-selective beta-blocker, atenolol is a selective (b1) beta-blocker, used for atrial fibrilation, arrhythmia --> anti-arrhythmatic drugs. reduces heart rate
• amlodipine is a calcium channel blocker, decreasing contractility --> used in heart failure, stemi or nstemi to reduce pressure on the heart
• arrhythmia first line is always beta-blockers
• In heart failure meds; a common goal is to increase intracellular calcium. digoxin inhibits the Na+/K+ ATPase pump. Milrinone blocks the breakdown of cAMP by inhibiting phosphodiasterise 3. inotropic agents do not increase the life expectancy in heart failure patients. Dobutamine acts on alpha 1 adrenergic receptors and beta 2 receptors on the heart, increasing contractility.
• the left coronary artery travels posterior to the pulmonary trunk from the ascending aorta
• Syphilitic aortitis is a disease of the aorta affecting the origins of the coronary arteries
• An increased heart rate will lead to a shorter diastole when most coronary blood flows
• A majority (40-50%) of MI will occur due to atherosclerosis or thrombotic occlusion of the left anterior descending artery
• Statins are inhibitors of HMG-CoA reductase, which is responsible for cholesterol synthesis, which reduces plaque inflammation
• Sympathetic stimulation can put physical stress on a plaque by causing vasoconstriction via adrenaline and hypertension, increasing the shearing forces, potentially leading to rupture
• Non-atherosclerotic causes of ischaemic heart disease:

  coronary spasms (e.g. vasospasms)coronary artery diseases (e.g. vasculitis)coronary artery thrombosis (e.g. DVT, aneurysm, infective endocarditis)substance abuse (e.g. cocaine --> leading to vasconstriction)
• Platelets are NOT involved in chronic inflammation. Plasma cells, lymphocytes and macrophages are.
• Oligodendrocytes provide the myelin sheath for axons in the CNS
• A foreign protein that can provoke an immune response is a

  Antigen
• Caffeine can provide extra Ca2+ for muscle contraction
• Pericytes are the contractile cells that surround capillaries and venules to regulate blood flow
• C-peptide is measured to determine if insulin has been produced by the body or injected. It is a waste product of synthesis.
• Atherosclerosis = large plaque accumulation

  Ateriosclerosis = wall thickening via calcification (ectesia) and plaque build up
• 90% of ischaemic heart disease is atherosclerotic. 10% non-atherosclerotic. Mechanisms are 1. Decreased oxygen supply to the myocardium, such as coronary obstruction. 2. increased o2 demand. 3. Anaemia, hyperthyroidism = worsens ischaemia; worsens O2 supply and demand, Hyperthyroidism increased metabolic rate and O2 demand
• Ischaemia = inadequate blood perfusion to tissue, resulting in an oxygen shortage
• Absolute and Relative ischaemic heart disease. Relative = stable angina (inc. o demands on exercise causes ischaemia) and intermittent claudication. Absolute = acute coronary syndrome, chronic ischaemic heart disease, Prinzmetal angina (never enough oxygen, even at rest)
• Three components of circulation are the pump (heart), blood vessels, and the lungs to provide oxygen
• 5 principal classes of cardiac disease; ischaemic HD (atherosclerotic etc), hypertensive HD, Valvular HD, Congenital HD (arrythmias, septal defects, etc), Non-ischaemic myocardial disease (cardiomyopathies etc)
• chordae tendineae prevent prolapse of atrioventricular valves during systole, preventing regurgitation
• Acute MI = SOB, dizziness, sweat, nausea, central chest pain radiating to arm, neck, jaw, potentially back, constant, doesn't ease with rest, often begins during exercise
• Stable angina will ease with rest and GTN. Includes SOB and dizziness, central chest pain
• Unstable angina doesn't improve upon rest, still treat with GTN but also constant monitoring to prevent MI
• Atherosclerosis is often asymptomatic until 90% occlusion
• Prinzmetal angina occurs due to abnormal coronary artery spasm, creating temporary coronary stenosis, leading to ischaemia. Occurs at rest, prompt response to nitrates.
• 20-40 minutes after onset of ischaemia, irreversible cardiac myocyte injury occurs. Angina lasts up to 15 minutes, which is why it is ischaemic, but without necrosis
• What is the initial event that leads to endothelial cell damage in a vessel wall?

  Endothelial cell damage to normal vessel wall
• What is the sequence of events that follows endothelial cell damage?

  Damage leads to an inflammatory response, increased endothelial permeability, and recruitment of monocytes that become macrophages
• How do LDL particles enter the vessel wall after endothelial damage?

  LDL enters through gaps in the endothelium