Additional information

[Put under action of autonomic system:] Arteries are thick walled and elastic. They contain stressed blood volume or volume under pressure. Veins are less elastic, walls are thinner and contain unstressed volume or blood volume under low pressures. Veins are capacitance vessels, are more compliant and carry the greatest amount of blood volume. Arterioles are muscular vessels with sympathetic innervation. They provide greatest resistance to blood flow. They have alpha 1 and beta 2 sympathetic receptors. Alpha 1 stimulation causes vasoconstriction and increase in peripheral resistance while stimulation of skeletal muscle vascular beta 2 receptors causes vasodilation and reduced peripheral resistance e.g. following exercise.

Frank-Starling Law: This law states that the cardiac muscle is able to increase its force of contraction in response to an increase in the length of the muscle fibre. In the heart, increased stretch on the muscle fibre will physiologically occur in response to an increase in venous return also called preload. That means that stroke volume will increase when venous return increases and vice versa. Stretching increases the sarcomere length and the sensitivity of troponin C to calcium. This causes increased cross bridge cycling and 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 if the afterload is increased or inotropy is decreased e.g. adding a calcium channel blocker drug.

Pressure-rate product: It is an indirect measure of the MVO2. It can be calculated as a product of the aortic systolic pressure and heart rate. It is an indicator of cardiac work and is influenced by the 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.

Box for phospholamban and diastolic dysfunction and lusitropy: Diastolic dysfunction is characterised by 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. Βeta 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. It is aided by SERCA. Improved sequestration also helps to release more Ca during the next depolarization improving the force of contraction. A defect in phospholamban will interfere with muscle relaxation as calcium levels in the cytosol will remain elevated. Such a defect will ultimately lead 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 the blood vessels and are used to treat hypertension e.g. amlodipine, nifedipine, nimodipine etc. 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 or cardiac cycle. It can be calculated by subtracting the end systolic volume from the end-diastolic volume or EDV - ESV. Cardiac output can be calculated by multiplying stroke volume and heart rate.

The heart spends ⅔ rd of the cardiac cycle in diastole and only ⅓ rd in systole. The 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. Normal range is from 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 increase in the heart rate in response to increase in the blood volume. The receptors are low pressure baroreceptors or volume receptors in the atria. Afferents travel via the vagus nerve to the nucleus tractus solitarius which activates the sympathetic outflow through the brainstem cardiovascular center leading to increase in heart rate and cardiac output. [Keep in mind that it is antagonistic to the baroreceptor reflex].

Cushing reflex: It 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. The increased intracranial pressure interferes with cerebral circulation which leads to hypoxia, hypercarbia and local acidosis, which in turn activate the central chemoreceptors which in turn activate the central sympathetic outflow. As a result, the blood pressure rises, often to dangerously high levels. The high blood pressure in turn activates the baroreceptors leading to bradycardia.