by the closing of the atrioventricular valves during ventricular contraction and is normally described as "lub". the second heart sound, s2, is the sound of the semilunar valves closing during ventricular diastole and is described as "dub". each sound consists of two components, reflecting the slight difference in time as the two valves close. s2 may split into two distinct sounds, either as a result of inspiration or different valvular or cardiac problems. additional heart sounds may also be present and these give rise to gallop rhythms. a third heart sound, s3 usually indicates an increase in ventricular blood volume. a fourth heart sound s4 is referred to as an atrial gallop and is produced by the sound of blood being forced into a stiff ventricle. the combined presence of s3 and s4 give a quadruple gallop. the x-axis reflects time with a recording of the heart sounds. the y-axis represents pressure. heart murmurs are abnormal heart sounds which can be either pathological or benign and there are numerous kinds. murmurs are graded by volume, from 1) the quietest, to 6) the loudest, and evaluated by their relationship to the heart sounds and position in the cardiac cycle. phonocardiograms can record these sounds. murmurs can result from narrowing (stenosis), regurgitation or insufficiency of any of the main heart valves but they can also result from a number of other disorders, including atrial and ventricular septal defects. one example of a murmur is still's murmur, which presents a musical sound in children, has no symptoms and disappears in adolescence. a different type of sound, a pericardial friction rub can be heard in cases of pericarditis where the inflamed membranes can rub together. heart rate main article: heart rate the resting heart rate of a newborn can be 120 beats per minute (bpm) and this gradually decreases until maturity and then gradually increases again with age. the adult resting heart rate ranges from 60–100 bpm. exercise and fitness levels, age and basal metabolic rate can all affect the heart rate. an athlete's heart rate can be lower than 60 bpm. during exercise the rate can be 150 bpm with maximum rates reaching from 200 and 220 bpm. cardiovascular centres autonomic innervation of the heart cardioaccelerator and cardioinhibitory areas. the wave of depolarization in a normal sinus rhythm shows a stable resting hr. following parasympathetic stimulation, hr slows. following sympathetic stimulation, hr increases. the normal sinus rhythm of the heart rate is generated by the sa node. it is also influenced by central factors through sympathetic and parasympathetic nerves: 116–22 of the two paired cardiovascular centres of the medulla oblongata. activity is increased via sympathetic stimulation of the cardioaccelerator nerves, and inhibited via parasympathetic stimulation by the vagus nerve. during rest vagal stimulation normally predominates as, left unregulated, the sa node would initiate a sinus rhythm of approximately 100 bpm. both sympathetic and parasympathetic stimuli flow through the paired cardiac plexus near the base of the heart. without any nervous stimulation, the sa node would establish a sinus rhythm of approximately 100 bpm. since resting rates are considerably less than this, it becomes evident that parasympathetic stimulation normally slows hr. the cardioaccelerator center also sends additional fibers, forming the cardiac nerves via sympathetic ganglia (the cervical ganglia plus superior thoracic ganglia t1–t4) to both the sa and av nodes, plus additional fibers to the atria and ventricles. the ventricles are more richly innervated by sympathetic fibers than parasympathetic fibers. sympathetic stimulation causes the release of the neurotransmitter norepinephrine (also known as noradrenaline) at the neuromuscular junction of the cardiac nerves. this shortens the repolarization period, thus speeding the rate of depolarization and contraction, which results in an increased heartrate. it opens chemical or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions. norepinephrine binds to the beta–1 receptor. high blood pressure medications are used to block these receptors and so reduce the heart rate. the cardiovascular centres receive input from a series of visceral receptors with impulses traveling through visceral sensory fibers within the vagus and sympathetic nerves via the cardiac plexus. among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors, plus stimuli from the limbic system which normally enable the precise regulation of heart function, via cardiac reflexes. increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. the cardiovascular centres monitor these increased rates of firing, suppressing parasympathetic stimulation or increasing sympathetic stimulation as needed in order to increase blood flow. similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. the cardiac centers monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex. with increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease sympathetic stimulation and increase parasympathetic stimulation. as pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation. there is a similar reflex, called the atrial reflex or bainbridge reflex, associated with varying rates of blood flow to the atria. increased venous return stretches the walls of the atria where specialized baroreceptors are located. however, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase hr. the opposite is also true. factors influencing heart rate in addition to the autonomic nervous system, other factors can affect this. these include epinephrine, norepinephrine, and thyroid hormones; levels of various ions including calcium, potassium, and sodium; body temperature; hypoxia; and ph balance . table 1: major factors increasing heart rate and force of contraction factor effect cardioaccelerator nerves release of norepinephrine proprioreceptors increased rates of firing during exercise chemoreceptors decreased levels of o2; increased levels of h+, co2, and lactic acid baroreceptors decreased rates of firing, indicating falling blood volume/pressure limbic system anticipation of physical exercise or strong emotions catecholamines increased epinephrine and norepinephrine thyroid hormones increased t3 and t4 calcium increased ca2+ potassium decreased k+ sodium decreased na+ body temperature increased body temperature nicotine and caffeine stimulants, increasing heart rate table 2: factors decreasing heart rate and force of contraction factor effect cardioinhibitor nerves (vagus) release of acetylcholine proprioreceptors decreased rates of firing following exercise chemoreceptors increased levels of o2; decreased levels of h+ and co2 baroreceptors increased rates of firing, indicating higher blood volume/pressure limbic system anticipation of relaxation catecholamines decreased epinephrine and norepinephrine thyroid hormones decreased t3 and t4 calcium decreased ca2+ potassium increased k+ sodium increased na+ body temperature decrease in body temperature factors that increase heart rate also trigger an increase in stroke volume. as with skeletal muscles the heart can increase in size and efficiency with exercise. thus endurance athletes such as marathon runners may have a heart that has hypertrophied by up to 40%.: 1063–64 the difference between maximum and minimum cardiac outputs is known as the cardiac reserve and this measures the residual capacity to pump blood. heart rates may reach up to 185–195 in exercise, depending on how fit a person is. cardiac output main article: cardiac output cardiac output as shown on an ecg cardiac output (co) is a measurement of the amount of blood pumped by each ventricle (stroke volume, sv) in one minute. to calculate this, multiply stroke volume (sv), by heart rate (hr), in beats per minute. it can be represented by the equation: co = hr x sv sv is normally measured using an echocardiogram to record end diastolic volume (edv) and end systolic volume (esv), and calculating the difference: sv = edv – esv. sv can also be measured using a specialized catheter, but this is an invasive procedure and far more dangerous to the patient. a mean sv for a resting 70-kg (150-lb) individual would be approximately 70 ml. there are several important variables, including size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload or edv, and afterload or resistance. normal range for sv would be 55–100 ml. an average resting hr would be approximately 75 bpm but could range from 60–100 in some individuals. using these numbers, (which refer to each ventricle, not both) the mean co is 5.25 l/min, with a range of 4.0–8.0 l/min. major factors influencing cardiac output - cardiac output is influenced by heart rate and stroke volume, both of which are also variable. svs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction. to calculate ejection fraction, sv is divided by edv. despite the name, the ejection fraction is normally expressed as a percentage. ejection fractions range from approximately 55–70 percent, with a mean of 58 percent. stroke volume major factors influencing stroke volume - multiple factors affect preload, afterload, and contractility, and are the major considerations influencing sv.summary of major factors influencing cardiac output - the primary factors influencing hr include autonomic innervation plus endocrine control. not shown are environmental factors, such as electrolytes, metabolic products, and temperature. the primary factors controlling sv include preload, contractility, and afterload. other factors such as electrolytes may be classified as either positive or negative inotropic agents. many of the factors that regulate the heart rate also affect cardiac function by altering the stroke volume. while a number of variables are involved, stroke volume is dependent upon the difference between end diastolic volume and end systolic volume. the three primary factors involved are preload, afterload and contractility. preload main article: preload (cardiology) preload is another way of expressing edv. therefore, the greater the edv, the greater the preload. a main factor is ventricular filling time. the faster the contractions are, the shorter the filling time and both the edv and preload are lower. the relationship between ventricular stretch and contraction has been stated in the frank-starling mechanism which says that the force of contraction is directly proportional to the initial length of muscle fibre. so that the greater the stretch of the ventricle the greater the contraction. any sympathetic stimulation to the venous system will increase venous return to the heart and ventricular filling. afterload the ventricles must develop a certain tension to pump blood against the resistance of the vascular system. this tension is called afterload. when the resistance is increased particularly due to stenotic valve damage the afterload must necessarily increase. a decrease in normal vascular resistance can also occur. different cardiac responses operate to restore homeostasis of the pressure and blood flow. contractility the ability of the myocardium to contract, (its contractility), controls the stroke volume which determines the end systolic volume. the greater the contraction the greater the stroke volume and the smaller the end systolic volume. positive or negative inotropic factors via sympathetic and parasympathetic stimulation respectively, can increase or decrease the force of contractions. sympathetic stimulation triggers the release of norepinephrine from the cardiac nerves and also stimulates the adrenal cortex to secrete both epinephrine and norepinephrine. these secretions increase the heart rate, subsequent metabolic rate and contractility. parasympathetic stimulation stimulates the release of acetylcholine (ach) from the vagus nerve which decreases contractility, and stroke volume which increases end systolic volume. several synthetic drugs have been developed that can act either as a stimulant or inhibitor inotrope. the stimulant inotropes, such as digoxin, cause higher concentrations of calcium ions which increase contractility. excess calcium (hypercalcemia) is also a positive inotrope. drugs that are negative inotropes include beta blockers and calcium channel blockers. hypoxia, acidosis, hyperkalemia are also negative inotropic agents. table 3: cardiac response to decreasing blood flow and pressure due to decreasing cardiac output baroreceptors (aorta, carotid arteries, venae cavae, and atria) chemoreceptors (both central nervous system and in proximity to baroreceptors) sensitive to decreasing stretchdecreasing o2 and increasing co2, h+, and lactic acid target parasympathetic stimulation suppressed sympathetic stimulation increased response of heart increasing heart rate and increasing stroke volume increasing heart rate and increasing stroke volume overall effect increasing blood flow and pressure