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Questions and Answers
Which of these statements regarding the signaling pathways involved in vascular smooth muscle contraction are TRUE? (Select all that apply)
Which of these statements regarding the signaling pathways involved in vascular smooth muscle contraction are TRUE? (Select all that apply)
Which of the following mechanisms does NOT contribute to the overall effect of nitric oxide (NO) on vascular smooth muscle relaxation?
Which of the following mechanisms does NOT contribute to the overall effect of nitric oxide (NO) on vascular smooth muscle relaxation?
Which of these medications would be most likely to directly inhibit vascular smooth muscle contraction by affecting myosin light chain phosphorylation?
Which of these medications would be most likely to directly inhibit vascular smooth muscle contraction by affecting myosin light chain phosphorylation?
Which of the following is most directly responsible for the physiological effect of increased intracellular calcium levels on vascular smooth muscle contraction?
Which of the following is most directly responsible for the physiological effect of increased intracellular calcium levels on vascular smooth muscle contraction?
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Which of these therapeutic strategies could potentially reduce cardiac oxygen demand? (Select all that apply)
Which of these therapeutic strategies could potentially reduce cardiac oxygen demand? (Select all that apply)
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Which of the following is a direct consequence of the activation of soluble guanylate cyclase (sGC) in vascular smooth muscle cells?
Which of the following is a direct consequence of the activation of soluble guanylate cyclase (sGC) in vascular smooth muscle cells?
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Which of the following statements accurately describes the relationship between Rho Kinase and myosin light chain phosphatase (MYPT) in vascular smooth muscle?
Which of the following statements accurately describes the relationship between Rho Kinase and myosin light chain phosphatase (MYPT) in vascular smooth muscle?
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Which of the following accurately describes the signaling pathway leading to smooth muscle contraction, starting with a signal at a smooth muscle receptor?
Which of the following accurately describes the signaling pathway leading to smooth muscle contraction, starting with a signal at a smooth muscle receptor?
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How does vasodilation affect coronary flow and oxygen supply?
How does vasodilation affect coronary flow and oxygen supply?
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What effect would a high heart rate (HR) typically have on myocardial blood flow?
What effect would a high heart rate (HR) typically have on myocardial blood flow?
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Which of the following factors contribute to vascular resistance in blood flow?
Which of the following factors contribute to vascular resistance in blood flow?
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What is the primary signaling mechanism that triggers smooth muscle contraction?
What is the primary signaling mechanism that triggers smooth muscle contraction?
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In the equation for coronary flow, what does the variable R represent?
In the equation for coronary flow, what does the variable R represent?
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Which class of drugs primarily helps to reduce cardiac workload by decreasing heart rate and contractility?
Which class of drugs primarily helps to reduce cardiac workload by decreasing heart rate and contractility?
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What is the primary effect of the Frank-Starling Mechanism on stroke volume?
What is the primary effect of the Frank-Starling Mechanism on stroke volume?
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Which of the following drug classes is primarily used for lipid lowering in patients with coronary artery disease?
Which of the following drug classes is primarily used for lipid lowering in patients with coronary artery disease?
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How do nitrates primarily impact coronary blood flow?
How do nitrates primarily impact coronary blood flow?
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Which of the following factors does NOT directly influence stroke volume according to the determinants of cardiac output?
Which of the following factors does NOT directly influence stroke volume according to the determinants of cardiac output?
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Study Notes
SIHD: Background
- SIHD (Stable Ischemic Heart Disease) is a condition where oxygen demand exceeds oxygen supply to the heart.
- This frequently arises from Coronary Artery Disease (CAD), characterized by plaque buildup in the coronary arteries.
- CAD leads to reduced blood flow, increasing oxygen extraction and potentially causing tissue hypoxia.
- Vasospasm (overactive vasomotor activity causing coronary contraction) can also cause ischemia, though less common than CAD.
- Acute coronary syndromes (ACS) like acute ischemia or myocardial infarction (heart attack) are distinct from SIHD. ACS results from plaque rupture or blood clots disrupting blood flow and oxygen supply, causing significant cell death.
- SIHD typically presents with stable angina (chest pain/pressure triggered by exertion, relieved with rest or nitroglycerin). Pain may also radiate to the arm, neck, back, and is often more common amongst women.
- SIHD is characterized by transient, resolved chest pain due to a stable atherosclerotic lesion. This contrasts with unstable angina, which is not resolved with rest or medication and often points to complex atherosclerotic issues or acute coronary syndromes (ACS).
- Variant angina (Prinzmetal's angina) is caused by vasospasm (spasms of the coronary arteries) that briefly inhibit blood flow.
Cardiac Cycle & Physiology
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Cardiac output (CO) is calculated as heart rate (HR) multiplied by stroke volume (SV).
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Stroke volume is dependent on preload, afterload, and contractility.
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Preload is the pressure filling the ventricles, directly influencing end-diastolic pressure and volume.
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Increased preload leads to increased stroke volume and cardiac output, following the Frank-Starling mechanism.
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Afterload is the pressure the heart faces when pumping blood out to the body.
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Higher afterload, for instance due to increased blood pressure, lowers stroke volume and cardiac output.
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Contractility is the force of contraction for a given sarcomere/fiber length.
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Factors impacting contractility include sympathetic and parasympathetic activity, inotropes (drugs that modulate contractility), and preload and afterload.
Cardiac Physiology
- Cardiac output is driven by the interplay of several factors: preload, afterload, contractility, and heart rate.
- Coronary blood flow is different in comparison to other vascular beds, often dramatically affected by changes in metabolic demand.
- Coronary blood flow is greatest under diastole and reduced under systole due to contraction of the heart.
- High heart rate reduces total coronary blood flow.
Myocardial Energy Demand
- Myocardial oxygen demand (the heart's oxygen needs) is balanced by oxygen supply.
- Demand is driven by factors such as heart rate, contractility, preload, and afterload.
- Supply is dependent on factors like heart rate, oxygen content of blood, and coronary perfusion.
Coronary Artery Disease (CAD)
- CAD involves a narrowing of the coronary arteries due to plaque formation.
- A reduction in coronary blood flow occurs.
- Increased O2 extraction and tissue hypoxia ensue.
- Severe obstructions (>70% narrowing) are typically implicated in significant O2 delivery impairments.
Three Categories of Coronary Ischemia
- Normal coronary artery
- Atherosclerosis
- Atherosclerosis with blood clot
- Coronary spasm
Plaques
- Atherosclerosis involves plaque formations in the arterial wall.
- Plaque structure comprises a fibrous cap, lipid-rich core, and cellular debris.
Mechanisms of CAD
- Endothelial injury initiates CAD.
- Lipid deposits and inflammation follow.
- Subsequent smooth muscle, inflammatory, and other cell reactions contribute to vessel occlusion.
- Plaque rupture potentially leads to vessel blockage.
Risk Factors for CAD/SIHD
- Age (>45),
- Sex (males, post-menopausal women),
- Family history,
- Smoking,
- High blood pressure,
- High cholesterol (LDL cholesterol),
- Diabetes,
- Sedentary lifestyle,
- Diet
Coronary Circulation and Blood Flow
- Coronary circulation is distinct in comparison to other vascular beds.
- Due to the heart's contraction during systole, blood flow significantly reduces compared to diastole, where blood flow peaks.
- Coronary blood flow is regulated to maintain a balance between myocardial oxygen supply and demand.
- Coronary A-VO2 difference is greater in the heart vs. systemic circulation.
Vascular Resistance and Blood Flow
- Blood flow (Q) is determined by the pressure gradient (∆P) divided by resistance (R) (Q = ∆P/R).
- Resistance in a vessel is proportional to blood viscosity (η), vessel length (L), and inversely proportional to the fourth power of the vessel radius (r4).
- Small changes in vessel radius can significantly affect blood flow.
Molecular Basis of Contraction/Dilation in Smooth Muscle
- Contraction: Ca++ influx, activation of MLCK which phosphorylates MLC proteins, initiating myosin filament activity, and muscle contraction.
- Dilation: NO diffuses to vascular smooth muscle cells, activating sGC to produce cGMP, which activates PKG, leading to relaxation through various pathways, including reduced Ca++ influx, decreased MLC phosphorylation, and increased K+ efflux.
Summary of VSMC (Vascular Smooth Muscle Cell) Signaling
- Vessel dilation/contraction impacts blood flow.
- Cardiac contraction/relaxation is tied to significant changes in flow.
- Signals from various substances (e.g. NO) control vascular dilation/contraction.
Summary of Cardiac Contractile Mechanisms
- Cardiac contraction is regulated by action potentials, channels in plasma membranes, rapid release of Ca++ from SR, Ca++ interaction with troponin, and subsequent activity, and restoration of resting state/membrane potential.
- Beta-adrenergic receptor (β-AR) signaling plays a crucial role in increasing cardiac contraction and output through multiple pathways, including activation of adenylate cyclase, cAMP production, and PKA phosphorylation of targets impacting Ca++ handling and potentially affecting the strength and frequency of activation.
Oxygen Consumption/Demand
- Oxygen consumption directly correlates with cellular respiration, specifically the metabolic process occurring in mitochondria.
- Factors affecting cardiac oxygen demand include heart rate, contractility, preload, afterload.
Myocardial Wall Stress and O2 consumption
- Pressure plays a crucial role in the balance between oxygen supply and demand in the heart.
Summary of SIHD Pathophysiology
- Stable Ischemic Heart Disease (SIHD) is a balance issue between the heart's oxygen supply and needs.
- Higher demand is due to increased Heart Rate, Preload, Afterload, and Contractility.
- Increased cardiac work requires higher oxygen needs.
Summary Coronary Circulation and O2 Demand
- Coronary circulation delivers oxygen to the heart muscles.
- Increased cardiac output correspondingly increases oxygen demand.
- Strategies to optimize oxygen supply and reduce demand are crucial in treating SIHD.
Excitation-Contraction (E-C) Coupling in Cardiac Muscle
- The process of E-C coupling in cardiac muscle describes the chain of events from stimulation to muscle contraction, involving action potentials, Calcium influx, activation of other systems including those within sarcoplasmic reticulum involved in Ca++ handling, and subsequent relaxation.
- Multiple steps in the process require large ATP amounts.
PKA Mechanisms in Modulating Ca++ Release
- PKA phosphorylation of targets like phospholamban (PLB) and ryanodine receptors (RyR) affects calcium signaling.
- Regulatory mechanisms exist that increase/decrease cardiac contraction.
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Description
This quiz covers the foundational aspects of Stable Ischemic Heart Disease (SIHD), including its relationship with Coronary Artery Disease (CAD) and acute coronary syndromes. Explore the symptoms, causes, and characteristics of SIHD, specifically focusing on stable angina and its clinical implications.
