Arteries, veins, and arterioles: Arteries have thick, elastic walls. They contain stressed blood volume (blood under higher pressure). Veins are less elastic, have thinner walls, and contain unstressed volume (blood under lower pressure). Veins are capacitance vessels: they’re more compliant and hold the greatest proportion of the total blood volume. Arterioles are muscular vessels with sympathetic innervation. They provide the greatest resistance to blood flow. They have α1 and β2 sympathetic receptors. α1 stimulation causes vasoconstriction and increases peripheral resistance, while stimulation of skeletal muscle vascular β2 receptors causes vasodilation and reduces peripheral resistance (e.g., following exercise).
Frank-Starling law: This law states that cardiac muscle can increase its force of contraction in response to an increase in muscle fibre length. In the heart, increased stretch of the muscle fibres occurs physiologically when venous return increases (also called preload). This means stroke volume increases when venous return increases, and decreases when venous return decreases. Stretching increases sarcomere length and increases the sensitivity of troponin C to calcium. This leads to increased cross-bridge cycling and greater muscle tension. A Frank-Starling curve can be drawn by plotting preload on the X axis and stroke volume on the Y axis. The curve shifts up when afterload is decreased or inotropy is increased (e.g., by adding digoxin). The curve shifts down when afterload is increased or inotropy is decreased (e.g., by adding a calcium channel blocker drug).
Pressure-rate product: This is an indirect measure of MVO2. It’s calculated as the product of aortic systolic pressure and heart rate. It indicates cardiac work and is influenced by ventricular wall tension. LaPlace’s law states that wall tension is directly proportional to ventricular radius and intraventricular pressure. Drugs that decrease afterload, heart rate, and inotropy are particularly effective in reducing MVO2 by reducing wall tension. Sympathetic stimulation increases MVO2.
Phospholamban, diastolic dysfunction, and lusitropy: Diastolic dysfunction is characterised by a slower relaxation rate of the ventricular muscle, leading to increased filling pressures, reduced cardiac output, and reduced velocity of contraction. Phospholamban is a phosphoprotein that mediates the β-adrenergic responses in the heart. β stimulation causes phosphorylation of phospholamban by protein kinase A, which increases SERCA pump activity. More calcium is sequestered back into the sarcoplasmic reticulum, leading to improved muscle relaxation. Lusitropy is the ability of the myocardium to relax after excitation-contraction coupling, and it’s aided by SERCA. Improved sequestration also helps release more Ca during the next depolarization, improving the force of contraction. A defect in phospholamban interferes with muscle relaxation because cytosolic calcium levels remain elevated. Such a defect ultimately leads to diastolic heart failure.
Calcium channel blockers: Calcium channel blockers bind to and block the L-type calcium channels. They are of two types: dihydropyridines and non-dihydropyridines. Dihydropyridines mainly act on blood vessels and are used to treat hypertension (e.g., amlodipine, nifedipine, nimodipine). Non-dihydropyridines are more cardioselective (e.g., diltiazem and verapamil).
Stroke volume, cardiac output, ESV, and EDV: Stroke volume is the amount of blood ejected by the heart with each heartbeat (cardiac cycle). It can be calculated by subtracting the end-systolic volume from the end-diastolic volume: EDV - ESV. Cardiac output can be calculated by multiplying stroke volume by heart rate.
The heart spends ⅔ of the cardiac cycle in diastole and only ⅓ in systole. Cardiac tissues receive their blood supply during diastole.
Ejection fraction (EF) is the fraction of end-diastolic volume that is ejected by the ventricle in each cardiac cycle. It is given by the formula Stroke volume / EDV. It is expressed as a percentage. The normal range is 55-70%. Low EF is seen in heart failure from any cause. High EF is seen in hypertrophic cardiomyopathy. It can be measured by echocardiography, MUGA scan, CT angiography, cardiac catheterization, or nuclear imaging techniques.
Bainbridge reflex: Also known as the atrial reflex, it involves an increase in heart rate in response to an increase in blood volume. The receptors are low-pressure baroreceptors (volume receptors) in the atria. Afferents travel via the vagus nerve to the nucleus tractus solitarius, which activates sympathetic outflow through the brainstem cardiovascular center, leading to increased heart rate and cardiac output. [Keep in mind that it is antagonistic to the baroreceptor reflex].
Cushing reflex: This is a protective response of the brain to maintain cerebral perfusion. It manifests as hypertension and bradycardia in response to increased intracranial pressure from any cause. Increased intracranial pressure interferes with cerebral circulation, leading to hypoxia, hypercarbia, and local acidosis. These changes activate the central chemoreceptors, which then activate central sympathetic outflow. As a result, blood pressure rises, often to dangerously high levels. The high blood pressure then activates the baroreceptors, leading to bradycardia.
Sign up for free to take 1 quiz question on this topic