Ischemic Chest Pain Flashcards
Angina Pectoris
Chest discomfort (pain, pressure, heaviness) resulting from myocardial ischemia; usually substernal Cause: Imbalance between O2 delivery and O2 demand
Associated terms:
Ischemic heart disease
Coronary artery disease
Coronary heart disease
Decreased coronary blood flow: vasospasm, fixed stenosis, and thrombus
Increased O2 consumption: increased HR, contractibility, afterload, and preload
Chronic Stable Angina
Caused by chronic narrowing of coronary arteries (fixed stenotic lesions) resulting from atherosclerotic disease
Pain occurs when myocardial oxygen demand increases (“demand ischemia”) aka during movement/exercise
Often associated with ST segment depression
Majority of patients have this
Variant (Printzmetal’s) Angina
Generally believed to be due to coronary artery vasospasm
Pain often occurs at rest but can be induced by stress (“supply ischemia”)
Usually produces ST segment elevation
Unstable Angina
Generally caused by spontaneous thrombus formation
Unpredictable pain: can occur at rest or during exercise (“supply ischemia”)
Troubling and related to development of MI and irreversible damage
Silent Ischemia
Asymptomatic myocardial ischemia
Detected via ECG
Often inducible or exacerbated by exercise (increase in demand)
Stress tests can aid in diagnosis
Patients don’t feel it because they lose nerve feeling in their heart
Myocardial Infarction
Irreversible damage to myocytes caused by prolonged ischemia and hypoxia as well as by reperfusion-induced injury
Cause: Occlusive thrombus usually resulting from plaque rupture in an epicardial coronary artery
Damaged tissue is initially composed of a necrotic core surrounded by a marginal (or border) zone that can recover or become irreversibly damaged
Some of the damage can actually come from reperfusion when blood flow is restored because of the metabolite build up within the blood causing damage
Myocardial O2 Balance Ratio
Myocardial Balance: O2 Supply (blood flow) compared to O2 Demand (workload)
Hypoxia results from a decreased ratio of O2 Supply/O2 Demand**
To Increase Oxygenation either increase supply and/or decrease demand and vice versa
Hypoxia leads to a failure of aerobic ATP production, cellular dysfunction and/or death
Causes of Reduced O2 Supply
Oxygen supply (delivery; DO2) to the myocardium is reduced by:
- Coronary artery disease: chronic stenosis, vasospasm, thrombosis
- Decreased CaO2: impaired oxygenation of blood (e.g., pulmonary edema, COPD, CO poisoning) and anemia
- Atherosclerosis, thrombosis, vasospasm, hypoxemia/anemia
Causes of Increased O2 Supply
Oxygen supply (delivery; DO2) to the myocardium is increased by:
- Increased Coronary Blood Flow***
- Increased CaO2 (only if abnormally low)
Factors that Increase MVO2
O2 Demand (MVO2) is increased by increasing afterload, HR, inotropy, and SV
MVO2 is most effectively reduced by: 1. Decreased Systolic Wall Stress (reducing afterload) 2. Decreased heart rate 3 Decreased inotropy 4. Decreased preload
O2 Extraction
O2 extraction is the difference between the arterial and venous O2 contents
The heart extracts nearly maximal available O2 from coronary blood (70-80% total) even at rest
Because O2 extraction by the heart is at maximum, increased O2 demand can only be met by increased blood flow
5 fold is increasing blood flow and 1 fold is increased O2 supply = coronary blood flow increases 6 fold during exercise
Coronary Flow Characteristics
Flow is greatest during diastole and driven by aortic pressure; it also decreases O2 demand
Flow is impeded during systole (extravascular compression)
High heart rates, by reducing diastole, limit diastolic flow
During exercise you spend more time in systole, so reduces flow through the vessels so dilation occurs as a compensatory mechanism to supply the heart with the increased O2 demand
Determinants of Coronary Vascular Resistance and Flow
Very low resistance in coronary vascular tree in normal conditions
Most of resistance occurs because of small smooth muscle, which contract during rest but more so during exercise
Extravascular compressive force during squeezing
R1 = large epicardial conduit arteries R2 = coronary resistance arteries and arterioles R3 = extravascular compressive force
Coronary Flow Reserve (Vasodilator Reserve)
Smooth muscle cells are relatively constrictive (normal patient) then with exercise there is an increase in O2 demand and they dilate
When max dilate from rest, difference in flow = flow reserve; increase 5 fold
Coronary Flow Reserve with Stenosis
Cardiac resistance vessels dilate to maintain resting flow with the stenotic lesion (exhausts dilatory reserve).
Patient with stenosis: say 80% (critical range), at rest they are down MAP, but response the downstream vessels are more dilated during rest like if they were exercise, so if they are already using up reserve, then not much more during exercise (exhaustion) and can only increase so much more (1-2 fold)
Use up flow reserve and don’t meet O2 demand
Metabolic Flow Control Mechanisms
Tissue vasodilator metabolites and ions:
1. Adenosine (product of ATP hydrolysis); especially important under hypoxic conditions
- K+ released during myocyte contraction (increased extracellular K+ causes vasodilation)
3 CO2 and H+ (increased by increase in MVO2; H+ also increased through anaerobic metabolism via lactate)
The products of increased energy consumption signal a resultant increased blood flow (and energy delivery)
They all signal for increased blood flow/vasodilation and override any other type of effects (sympathetic E/NE for example); occurs throughout the body, not just the heart
Like the leg, the heart will dilate the downstream vessels to compensate for stenosis
Increase in flow from downstream dilation, greater pressure drop across the stenotic lesion = lead to vascular steal
Vascular Endothelial Mechanisms of Flow Regulation
Vascular endothelium is an important source for synthesis and release of vasoactive substances: Nitric oxide (NO) Endothelium-derived hyperpolarizing factor (EDHF) Endothelin-1 (ET-1) Prostacyclin (PGI2)
Endothelial cells have receptors for various ligands and also sense level of blood flow occurring in the vessels and regulate vasoconstriction and dilation
*All the above cause vasodilation
Nitric Oxide Formation
Increasing blood flow it increases shear force: increase Ca2+ level to increase NO synthase to get increase in NO
Also have signaling substances like ACh, bradykinin, substance P, and insulin to do this as well
Septic shock: increase iNOS to increase NO (iNOS = synthase)
cGMP: not fully understood but increasing in K+ influx that causes dilation
Some Important Actions ofNitric Oxide
Vasodilation: flow-dependent and flow-independent smooth muscle relaxation (vasodilation) and inhibits vasoconstrictor influences (e.g., sympathetic, humoral)
Anti-thrombotic: inhibits platelet adhesion to vascular endothelium
Anti-inflammatory: inhibits leukocyte adhesion to vasculature and scavenges superoxide radicals
Coronary Endothelial Dysfunction
Endothelial dysfunction in coronary artery disease decreases NO production or bioavailability, which can lead to:
Loss of flow-dependent vasodilation
Vasospasm
Thrombosis
Leukocyte adhesion & local inflammatory responses (proatherogenic)
These factors increase MI/stoke risk
Very poor prognosis because development of MI and angina over time
Conditions Associated With Decreased NO Production and/or Bioavailability
Hypertension Obesity Dyslipidemias Diabetes Heart Failure Other (e.g., age, atherosclerosis, cigarette smoking, injury, infection and inflammation)
Endothelin
Potent vasoconstrictor
ET-1 release stimulated by AII, ADH/vasopressin, ·O2-, shearing forces, cytokines, thrombin
ET-1 release inhibited by NO, PGI2, and ANP
Linked to pathogenesis of hypertension, coronary vasospasm, heart failure
Coronary Vascular Steal
Similar to peripheral vascular steal, multiple lesions can lead to coronary steal
If the vasculature supplied by the LAD is maximally dilated, then physical activity or vasodilator drugs may cause LAD flow to decrease as CFX flow increases
Must have multiple stenotic lesions
Pressure drop across first lesion and then when start to exercise the downstream circumflex vessels dilate to further drop the P2 pressure because of the CFX and then across second lesion get even more reduced P3 pressure and blood flow drops below resting levels
