4. Ischaemic Heart Disease Flashcards
What is ischamia?
An inadequate supply of blood to a tissue resulting in insufficient supply of oxygen and other metabolic needs for that tissue
What is infarction?
Cell/Tissue necrosis caused by an inadequate supply of blood carrying oxygen and other metabolic needs
What may cause blockage of an artery
-Atheroma
-Thrombus
-Spasm
-Embolus
-Vasculitis
What factors determine myocardial oxygen supply
-Coronary blood flow (determined by perfusion pressure, vascular resistance, and diastole duration)
-Oxygen content of blood (determined by arterial oxygen saturation, haemoglobin conc and PPO2)
-Coronary vasodilation (determined by endothelial factors, metabolic demand, and auto regulation)
-External compression (determined by myocardial contraction and left ventricular hypertrophy)
What factors determine myocardial oxygen demand
-Heart rate (faster contractions shorten diastole, reducing coronary perfusion whilst increasing energy consumption)
-Higher contractility (increases ATP consumption, raising oxygen demand)
-Ventricular wall stress
Describe the differences in large coronary arteries (epicardial) between healthy and angina patients
-Healthy individuals have normal vessel diameter with intact endothelial function, proper vasodilation in response to nitric oxide (NO) and metabolic demand.
-Angina patients have narrowed coronary arteries due to atherosclerosis, with fixed stenosis limiting blood flow (especially during exertion). Endothelial dysfunction lead to reduced NO release
Describe the differences in large coronary arterioles (microcirculation) between healthy and angina patients
-Healthy individuals function, with arterioles dilating appropriately to match oxygen demand
-Angina patients have microvascular dysfunction reducing ability of arterioles to dilate. Even if large arteries are normal, small vessels fail to increase perfusion, causing chest pain without significant epicardial stenosis
Describe the mechanism of action of nitrates in the treatment of angina
Prodrugs that release nitric oxide leading to:
-Venodilation, decreasing preload. This decreases ventricular wall stress, lowering oxygen demand.
-Mild arterial dilation, decreasing afterload. This reduces systemic vascular resistace, lowering myocardial workload and oxygen demand.
-Coronary vasodilation, increasing oxygen supply. This causes epicardial artery dilation, improving blood flow in ischaemic areas, increasing oxygen supply.
Give some examples of types of nitrate used to treat angina
-Glyceryl Trinitrate (GTN)
-Isosorbide dinitrate (ISDN)
-Isosorbide mononitrate (ISMN)
Describe the cellular mechanism of action of nitrates in the treatment of angina
-Nitrates are metabolised releasing NO
-Activating guanylyl cyclase, increasing cGMP
-Dephosphorylation of myosin light chains
-Reducing cytoplasmic Ca2+
-Relaxing smooth muscle
Give some common side effects of nitrates in the treatment of angina?
-Headache (due to cerebral vasodilation)
-Hypotension and dizziness (especially postural)
-Reflex tachycardia (due to sympathetic activation)
Describe contraindications associated with nitrates in the treatment of angina?
-Severe hypotension (systolic < 90mmHg)
-Right ventricular infarction (reduces preload too much)
-PDE5 inhibitors (risk of severe hypotension and cardiovascular collapse)
Name the key goals in the initial treatment of a myocardial infarction
-Relieve hypoxia
-Pain relief
-Reduce cardiac workload and improve perfusion
-Reduce risk of another infarction
How may we relieve hypoxia during myocardial infarction?
Deliver oxygen by mask
How may we relieve pain during a myocardial infarction?
-Morphine/diamorphine
-With an antiemetic
-Relieving pain and nausea
-And causing ventilation
How may we reduce cardiac workload during a myocardial infarction?
-Give nitrates (eg GTN)
-Acting as a vasodilator
How may we reduce the risk of another infarction during a myocardial infarction?
-Antiplatelet
-eg aspirin, clopidogrel
Name the key goals in the subsequent treatment of a myocardial infarction
-Improve myocardial perfusion and reduce risk of arrhythmias
-Reduce risk of heart failure/left ventricular dysfunction
-Protect from thrombus in at risk patients
How may we improve myocardial perfusion and reduce risk of arrhythmias following myocardial infarction?
-Deliver beta blockers
-Lengthens diastole
How may we reduce risk of heart failure/left ventricular dysfunction following myocardial infarction?
-Utilise ACE inhibitor
-eg Captopril
How may we protect from thrombus following myocardial infarction?
-Use anticoagulants
-eg Heparin
