Blood enters the left atrium from the pulmonary vein. The pulmonary vein is the only vein in the body that carries oxygenated blood. Blood in the left atrium flows into the left ventricle through the atrioventricular (AV) valve located at the juncture of the left atrium and ventricle. This valve is called the mitral valve. All cardiac valves open when pressure in the chamber or vessel above them is greater than the pressure in the chamber or vessel below.

Blood from the left ventricle outflows into a large, muscular artery, called the aorta, through the aortic valve. Blood in the aorta is delivered throughout the systemic circulation, through arteries, arterioles, and capillaries, which then rejoin to form veins. The veins from the lower part of the body return the blood to the largest vein, the inferior vena cava. The veins from the upper body return blood to the superior vena cava. The venae cavae empty into the right atrium.

Blood in the right atrium moves into the right ventricle through another AV valve, called the tricuspid valve. Blood leaves the right ventricle and travels through a fourth valve, the pulmonary valve, into the pulmonary artery. The pulmonary artery is the only artery in the body that carries unoxygenated blood. The pulmonary artery branches into left and right pulmonary arteries, which travel to the left and right lungs, respectively. In the lungs, the pulmonary arteries branch many times into arterioles and then capillaries. Each capillary perfuses past an alveolus, the unit of respiration. All capillaries reform to become venules, and the venules become veins. The veins join to form the pulmonary veins.

Blood flows in the pulmonary veins back to the left atrium, completing the blood flow cycle. The heart and the systemic and pulmonary circulations are shown in Figure 13-1.

As blood passes each cell of the body in the systemic circulation, carbon dioxide and other cellular waste products are added to the blood, while oxygen and nutrients are delivered from the blood to the cells. In the pulmonary circuit, the opposite occurs: carbon dioxide is eliminated from the blood and oxygen is added. By continual cycling of the blood through the pulmonary and systemic circulations, oxygen supply and waste removal are ensured for all cells.

Two large arteries, called the left and right coronary arteries, branch off the aorta as soon as it leaves the left ventricle and supply blood to the heart. The left coronary artery quickly branches into the left anterior descending artery and the circumflex artery. Table 13-1 summarizes the portions of the heart supplied by the coronary arteries.

As described fully in Chapter 10, cardiac muscle fibers are made up of bands of protein filaments, called myofilaments, lying in series with each other. Each band is called a sarcomere. A cardiac sarcomere is shown in Figure 13-2. Sarcomeres in cardiac muscle are fused together at their borders to form areas called intercalated disks. These are areas of low resistance across which electrical currents can pass.

Each cardiac sarcomere is made up of thick and thin filaments. Thick filaments consist of the contractile protein myosin. Thin filaments include the second contractile protein, actin, and two regulatory proteins, tropomyosin and troponin. Cross-bridges extend from the myosin filaments to the actin filaments. In the absence of calcium ion, tropomyosin is attached to each actin molecule in such a way that tropomyosin covers the binding site for myosin on actin, and thus inhibits cross-bridge connection. The troponin complex, which includes troponin-I, -T, and -C, is attached to the tropomyosin filament. When calcium is available, troponin-C binds the tropomyosin filament in such a way that the myosin cross-bridges are now exposed and able to bind actin.

At this point, energy stored from a previous myosin-based reaction, in which adenosine triphosphate (ATP) was split into adenosine diphosphate (ADP) and a phosphate molecule, is released and is used to swing the crossbridges. This causes the myosin and actin filaments to slide past each other and muscle contraction to occur. Because all cardiac muscle cells are connected to each other at the intercalated disks, depolarization of one group of cardiac muscle cells spreads to neighboring cells and all cells contract as a unit. Each contraction represents a heartbeat.

An action potential in a cardiac muscle cell is triggered as a result of a depolarizing current reaching it from a neighboring muscle cell. Although in some ways similar to a skeletal muscle action potential, the cardiac action potential is unique due to its plateau phase and long duration.

Just like a skeletal muscle cell, a cardiac muscle cell fires an action potential when the inside of the cell becomes significantly more positively charged than the outside. As in skeletal muscle, this occurs when voltage-sensitive sodium channels open in the cell membrane, resulting in an in-rush of positively charged sodium ions. This is called Phase 0 of the cardiac action potential and is characterized by a rapid change in the membrane potential, from about -80 mV intracellularly to a positive intracellular value of approximately 20 to 25 mV (Fig. 13-3). Very quickly, closure of the sodium channels occurs, marking the end of Phase 0. Next begins Phase 1, a repolarizing phase. During Phase 1, potassium channels close in the cell membrane and positively charged potassium ions accumulate in the cell, preventing the return of the membrane potential toward its resting (negative) value. Closure of the potassium channels immediately following the onset of the action potential does not happen in skeletal muscle; in cardiac muscle, it contributes to the slowing of repolarization. Prolongation continues during the next
phase, Phase 2, as calcium ions begin to enter the cell through calcium channels present in the cell membrane. This increase in intracellular calcium triggers the opening of other, slow calcium channels located in the membrane of the sarcoplasmic reticulum, a storage compartment for intracellular calcium. This process, called “calcium stimulated calcium release,” results in a further rise in intracellular calcium levels, reaching levels that effectively move the troponin off the tropomyosin molecule and thus trigger the muscle cell to contract. The slow inward movement of calcium also prolongs cellular depolarization. Phase 3 is the final repolarization phase, and it occurs when the influx of calcium decreases and the outflow of potassium ions through “delayed rectifier channels” begins, finally bringing the membrane potential back to its negative resting value. Intracellular levels of calcium decrease, by means of calcium moving out of membrane channels as well as via active transport of calcium back into the sarcoplasmic reticulum storage sites. As calcium falls, the cell relaxes and the heart enters diastole. The cell remains in Phase 4, the resting potential phase, until it is again stimulated to undergo an action potential. Prolongation of the action potential is significant because it makes it impossible to fire a second action potential before the first is completed, ensuring that cardiac cells will not undergo summation and tetany of contractions: If cardiac cells underwent tetany, the heart would stop pumping out blood because it would not be able to relax and fill with blood between beats.

Adenosine diphosphate (ADP) releases from the cross-bridge after it swings, and another ATP molecule binds to the myosin protein, causing the myosin cross-bridges to separate from actin. As long as calcium ion is still available intracellularly to bind troponin, this new ATP will be split, and its energy will be released when a new cross-bridge connection forms, thereby repeating the cycle and ensuring that the muscle will continue to contract. Many crossbridge cycles and sliding of the filaments occur during one action potential. The contraction ultimately stops when intracellular calcium levels fall. Without calcium, tropomyosin again blocks the site on actin to which the crossbridges bind, and no further connection between myosin and actin can be made.

In skeletal muscle, there is always enough calcium released with each action potential to fully saturate all troponin sites and thus cause all cross-bridges to swing. In cardiac muscle, however, less than maximal amounts of calcium are usually released with a single action potential. This means that under certain circumstances, cardiac contractile strength may be increased if necessary.

Most cardiac muscle cells have the capacity to fire action potentials independently. However, certain cells are more permeable to sodium ions at rest than others, and therefore start off more positively charged than other cells. These slightly depolarized cells reach action potential threshold and fire sooner than other cells. The fast-firing cells pass their excitation easily to other cells through the connections between each cell. The fastest depolarizing cells of the heart control the rate, or pace, of contraction. The cells that normally depolarize fastest make up the SA node. The SA node, located in the wall of the right atrium, is the primary pacemaker of the heart.

From the SA node, depolarization spreads rapidly through both atria and soon reaches the AV node, which is located in the lower right atrium near the juncture of the atria and ventricles. When the depolarization reaches the AV node, the electrical signal is delayed shortly before it is passed to the ventricles. During this delay, the atria reach action potential threshold and begin to contract, pumping their last bit of blood into the ventricles. While contraction of the atria is occurring, the electrical depolarization spreads through the AV node down specialized muscle fibers to an area of the ventricles called the bundle of His. Depolarization then spreads rapidly through the left and right bundle branches of the interventricular septum, and from there, down an extensive, wide-reaching group of specialized conducting fibers called Purkinje fibers. In a normal heart, the apex of the ventricle depolarizes first, after which the wave
of depolarization spreads up toward the atria. This wave allows for the efficient ejection of blood from the ventricle.

The length of cardiac muscle fibers affects the tension they can produce because of the anatomic arrangement of muscle contractile proteins. In the resting heart, the muscle fibers are stretched to a degree less than that required to produce maximum tension. When cardiac muscle fibers are stretched, more myosin cross-bridges can reach their actin-binding sites, causing an increase in cross-bridge swinging and an increase in cardiac tension and cardiac contractility. This results in an increase in stroke volume and cardiac output (Equation 13-1). Increased stretch of the myofibrils occurs when there is increased filling of the heart; therefore, the tension that is produced by the heart is
proportional to the volume of blood in the heart immediately before ventricular contraction: the end-diastolic volume (also referred to as preload). Because of this response, the heart has reserve capacity to pump more forcefully when the volume of blood flow is increased—for example, with exercise and volume loading.

Because an increase in venous return will increase end-diastolic volume, the length-tension relationship of the heart ensures that under most conditions, increased blood flow into the heart will be matched by increased blood pumped out. This serves to return the end-diastolic volume back toward normal, making this response typically of short duration. This intrinsic response of the heart to its own muscle fiber stretch is called Starling’s law of the heart, after Frank Starling, the physiologist who first described it. The length-tension relationship of a normal heart under nonstimulated control conditions is shown in the lower curve of Figure 13-4. Note that, unlike in the skeletal muscle length-tension curve, the normal heart does not fall off the curve at higher fiber length.

The words “under most conditions” in the preceding paragraph refer to the fact that in a damaged heart, overstretch of the ventricle will not improve contractility, and the heart will not be able to pump out the extra blood. Therefore, a damaged heart continues to overfill and eventually becomes overstretched. This situation is characteristic of heart failure, which is described later.

A second reason why the stretch of cardiac muscle fibers determines cardiac output is that with increased venous return, the wall of the right atrium is stretched. This stretch causes an increased firing rate of the SA node and an increased heart rate of up to 20%. This increase in heart rate, coupled with an
increase in stroke volume as a result of extra filling, can dramatically increase cardiac output. However, as mentioned earlier, because an increase in end-diastolic volume increases stroke volume, the intrinsic response to excess volume is usually temporary.

Heart rate and stroke volume are affected by the sympathetic and parasympathetic nervous systems and by circulating hormones.

Sympathetic nerves travel in the thoracic spinal nerve tracts to the SA node and release the neurotransmitter norepinephrine. Norepinephrine binds to specific receptors called β1 adrenergic receptors, present on the cells of the SA node. When this happens, activation of a second messenger system causes increased firing rate of the node, leading to an increase in heart rate. The heart rate is decreased if the activation of the sympathetic nerves and the release of norepinephrine are reduced. An increase or decrease in the heart rate is called a positive or negative chronotropic effect.

Sympathetic nerves also innervate cells throughout the myocardium, causing an increase in the force of each contraction (i.e., the contractility) at any given muscle fiber length. This causes an increase in stroke volume and is called a positive inotropic effect, as shown by the upper curve in Figure 13-4.

Parasympathetic nerves travel to the SA node and throughout the heart through the vagus nerve. Parasympathetic nerves release the neurotransmitter acetylcholine, which slows the rate of depolarization of the SA node and leads to a decrease in heart rate—a negative chronotropic effect. Parasympathetic stimulation to other sites in the myocardium appears to reduce contractility and therefore stroke volume, producing a negative inotropic effect.

Hormonal control of cardiac output mainly involves the adrenal medulla, an extension of the sympathetic nervous system. With sympathetic stimulation, the adrenal medulla releases norepinephrine and epinephrine into the circulation. These hormones travel to the heart and produce positive chronotropic and inotropic responses.

Immediately proximal to the capillaries are the meta-arterioles, which deliver blood to the capillaries through a precapillary sphincter. The precapillary sphincter is a smooth muscle fiber encircling the entrance to the capillary. This fiber is not innervated by nerves, but responds to hormonal and local mediators of blood flow.

Bulk flow is the movement of a fluid as a result of a pressure gradient from high to low. In the vascular system, fluid moves back and forth between the capillaries and the interstitial fluid. Interstitial fluid is a plasmalike filtrate surrounding all cells. It can store fluid in times of high plasma volume, or resupply the vascular system in times of plasma loss.

There are four forces affecting the bulk flow of fluid across a capillary into the interstitial space. They include capillary pressure, interstitial hydrostatic pressure, plasma colloid osmotic pressure, and interstitial fluid colloid osmotic pressure.

Capillary hydrostatic pressure is the remainder of the mean arterial pressure generated by the heart. For most capillaries, this pressure averages approximately 18 mm Hg over the length of the capillary (Fig. 13-5), with pressure at the arteriolar end (28 mm Hg) significantly greater than the pressure at the venous end (10 mm Hg). Capillary pressure is a reflection of mean blood pressure.
Therefore, if blood pressure increases, capillary pressure increases. If blood pressure decreases, capillary pressure decreases. Capillary pressure favors filtration of plasma out of the capillary into the interstitial space.

Interstitial hydrostatic pressure is the pressure exerted by fluid in the interstitial space. Interstitial hydrostatic pressure is primarily caused by water. If positive, it opposes filtration of plasma out of the capillary; if negative, it draws fluid out of the capillary. Recent research suggests that the pressure is negative in most tissues, averaging approximately 3 mm Hg. In some tissues, it may be positive and oppose filtration.

Plasma (capillary) colloid osmotic pressure refers to osmotic pressure exerted by plasma proteins. Plasma colloid pressure opposes filtration of plasma out of the capillary. This pressure develops when water is pushed out of the capillary by the hydrostatic pressure and the proteins are too large and too charged to follow. The concentration of protein left behind increases, causing an increase in osmotic pressure. This pressure serves to draw water back into the capillary. Plasma colloid osmotic pressure in most capillaries averages approximately 28 mm Hg.

Interstitial fluid colloid osmotic pressure is normally a small force. Few proteins escape across the capillary into the interstitial compartment. Those that do are rapidly taken up into vessels of the lymph system. The lymph vessels return the proteins to the bloodstream by delivering them into the vena cava and the right atrium. Interstitial fluid colloid osmotic pressure averages approximately 8 mm Hg.

Adding up the forces, filtration (18 + 3 + 8 mm Hg = 29 mm Hg) nearly balances reabsorption (28 mm Hg) and little net movement of fluid across the capillary occurs (see Fig. 13-5). Extra fluid in the interstitial space is reabsorbed by the lymph flow.

Pressure at the beginning of the aorta is generated by the left ventricle. This pressure varies between approximately 120 mm Hg during systole and 80 mm Hg during diastole. Because diastole lasts longer than systole, the average, or mean, blood pressure equals approximately 40% of systolic pressure plus 60%
of diastolic pressure. The systolic pressure represents the maximum pressure on the aorta and major vessels and the diastolic pressure reflects the minimum pressure on the arteries. The difference in the systolic and diastolic pressure is referred to as pulse pressure.

As blood moves through the large and small arteries, some pressure is lost. Much more is lost as blood traverses the arterioles and capillaries. By the time blood flow reaches the capillary, blood pressure at the arteriole end of the capillary has decreased to approximately 35 mm Hg for most capillary beds. With movement through the capillary, this pressure decreases to 10 mm Hg at the venous end, resulting in a mean blood pressure in the capillary of approximately 18 mm Hg. By the time the blood reaches the vena cava, the pressure is zero.

Thus, the pressure gradient affecting flow is large between the aorta and the vena cava (90 to 0 mm Hg). This is the force that drives the blood through the systemic circulation.

Resistance to flow through a vessel depends on the length and radius of the vessel, and on the viscosity of the fluid. In the body, the length of the blood vessels is essentially fixed. Although potentially variable, blood viscosity is also fixed. Therefore, when discussing resistance to blood flow in the vascular system, one usually considers only the radius of the blood vessels. Because of the dynamics of flow through a tube, a small decrease in the radius causes an enormous increase in resistance to flow. This is true both for blood flowing through a blood vessel and for water flowing through a hose or a pipe.

The smaller the vessel, the greater the effect narrowing that vessel has on blood flow. Varying the radius of the large arteries does not significantly affect blood flow. Likewise, because veins are so distensible, they offer little resistance to flow. Instead, resistance to blood flow is determined by the radius of the arterioles, thus making the arterioles the resistance vessels of the cardiovascular system.

Narrowing an arteriole decreases blood flow downstream into the capillaries and veins fed by that arteriole, backing up the blood upstream. Because blood pressure depends on blood flow, narrowing the arterioles decreases blood pressure downstream and increases blood pressure upstream.

In contrast, if the arterioles are dilated, flow increases, resulting in increased downstream pressure and decreased pressure upstream. With the dilation, force is decreased. Control of arteriole diameter is an intricate balance between local effects and nervous and hormonal stimulation.

Blood pressure is continually monitored by sensors called baroreceptors (pressure receptors). There are baroreceptors in the carotid artery (in the neck) and in the aortic arch where the aorta leaves the heart; these sensors are called the carotid and aortic baroreceptors, respectively. There are baroreceptors located
in the arterioles supplying the kidney nephrons. Receptors in both atria and in the pulmonary artery also respond to changes in pressure. Because the atrial and pulmonary artery receptors are in low-pressure areas of the vasculature, they are called low-pressure receptors.

All baroreceptors act as stretch receptors that respond to changes in blood pressure. Their stretch increases with increased blood pressure. This stretch increase causes afferent neurons receiving information from the receptors to increase their rate of firing. These neurons travel to the brain and innervate its cardiovascular center. A decrease in blood pressure decreases the stretch of the baroreceptors, which reduces the firing of the afferent nerves innervating the cardiovascular center.

Chemoreceptors located in the carotid bodies and the aorta, respond to changes in oxygen, carbon dioxide, and hydrogen ion concentration in arterial blood. Low blood pressure, decreased oxygen, or accumulation of metabolic end products stimulates the sympathetic nervous system causing the chemoreceptors and baroreceptors to respond and signal the brain. When blood pressure drops, the parasympathetic nervous system is inhibited and the sympathetic system is stimulated to increase heart rate. Chemoreceptors cause vasoconstriction and play a vital role in ventilation (see Chapter 14).

The cardiovascular center in the brain is part of the reticular formation and is located in the lower medulla and pons. This center is the site of neural control for blood pressure regulation. If a change in blood pressure has occurred, the cardiovascular center activates the autonomic nervous system, leading to changes in sympathetic and parasympathetic stimulation to the heart and sympathetic stimulation to the entire vascular system. Resistance of the vasculature is altered and blood flow and blood pressure are affected.

Sympathetic nerves stimulate heart rate and contractility by binding to β1 receptors in the heart. Parasympathetic nerves decrease heart rate by binding to cholinergic receptors. In addition, sympathetic nerves traveling in the thoracic and upper lumbar spinal tracts influence blood pressure by exerting control over virtually the entire peripheral vascular system (except the capillaries) through innervation of the tunica media (the smooth muscle).

At most blood vessels, sympathetic nerves release norepinephrine, which binds to specific receptors on the smooth muscle cells, called alpha (α) receptors. Stimulation of the α receptors causes the smooth muscle to contract, constricting the vessel, which increases TPR and therefore increases blood pressure.

Blood vessels supplying skeletal muscle have a different type of receptor, called beta2 (β2) receptors, which, when stimulated by norepinephrine, cause the
vessels to relax. It appears that this sympathetic vasodilatory response plays a significant role only in the anticipatory response to exercise, perhaps serving to prime the skeletal muscle with oxygen and nutrient support before exercise onset.

Skeletal muscle blood vessels also possess receptors for acetylcholine. These receptors are called muscarinic receptors and do not appear to be innervated by parasympathetic neurons. However, they respond to acetylcholine released by certain sympathetic cholinergic neurons. These neurons also supply the vascular smooth muscle in skeletal muscle and cause relaxation of the vessels, thus increasing blood flow through these vessels.

There are several hormones that control the resistance of the vascular system. These hormones are released directly in response to changes in blood pressure, in response to neural stimulation, or both.

With a decrease in blood pressure, baroreceptor information is transmitted to the cardiovascular center in the brain. This causes the stimulation of sympathetic output to the heart and vascular system, increasing heart rate and TPR. Parasympathetic output is decreased, also increasing heart rate. Renin release increases, causing increased angiotensin II, which directly increases TPR and aldosterone synthesis. Increased aldosterone increases sodium reabsorption and, in the presence of ADH, water reabsorption. Increased plasma volume, stroke volume, and cardiac output result. Capillary pressure decreases directly with blood pressure and indirectly from sympathetic constriction of the arteriole
feeding the capillary. This serves to decrease filtration of fluid out of the capillary. All of these responses serve to increase blood pressure toward normal, by increasing heart rate, stroke volume, and TPR (Fig. 13-6).

In contrast, if blood pressure increases, baroreceptor responses cause a decrease in sympathetic stimulation to the heart and vascular smooth muscle, and heart rate and TPR decrease. Increased parasympathetic stimulation to the heart contributes to the decrease in heart rate. There is a decrease in renin and ADH release, reducing TPR and plasma volume. ANP release increases. All these responses serve to decrease blood pressure toward normal.

Although hormonal and neural mechanisms can quickly regulate blood pressure, the effect is short-term. The kidneys are responsible for long-term blood pressure control by regulating extracellular fluid volume (ECF). For example, in response to ECF from increased water and sodium retention, the kidney responds by increasing the excretion of water and sodium. Autoregulation of blood flow also impacts how fluid volume affects blood pressure.

Several theories are proposed to explain local control of blood flow. The most widely accepted is that chemical mediators are released by metabolizing cells that bind to meta-arterioles or precapillary sphincters, causing them to open or shut to blood flow.

Chemical mediators that control local blood flow include adenosine (a metabolite of ATP), carbon dioxide, histamine, lactic acid, potassium ions, and hydrogen ions. All of these substances except histamine are by-products of metabolism; as cell metabolism increases, so do their concentrations. This serves to match increased metabolic activity with increased blood flow. Mast cells present throughout the interstitial space release histamine in response to immune stimulation or local injury. Adenosine appears to particularly regulate local blood flow in the heart.

An alternative theory concerning local control suggests that the meta-arterioles and capillary sphincters sense an oxygen or nutrient deficit that causes them to relax, thereby increasing blood flow to the surrounding cells.

Various other chemicals are released by the blood vessels or by mediators of inflammation or healing, which affect blood flow to an area.

The lymph system consists of small capillaries that drain into larger lymph vessels. Like blood vessels, these larger vessels are composed of smooth muscle and endothelial cells. Lymph from the lower body flows up the thoracic duct and empties into the left jugular and subclavian veins. Lymph flow from the left arm, shoulder, and left side of the head travels through the thoracic duct and then into the left jugular and subclavian arteries. Lymph flow from the right arm and right side of the neck and head empties into the right jugular and subclavian veins. The lymphatic system is illustrated in Figure 13-7.

Movement of lymph results from contraction of the smooth muscle lining the lymph vessels in response to its stretch, and the pumping action of the surrounding skeletal muscles. Valves present in lymph vessels prevent backflow.

The lymph system has three essential roles in the body, all of which depend on the greater permeability of lymph capillaries compared to blood capillaries.

First, lymph capillaries retrieve any proteins that escape from the capillaries into the interstitial fluid. These proteins move easily into lymph vessels and are then returned to the blood circulation via the thoracic duct. This is essential because it allows interstitial colloid osmotic pressure to remain low. If proteins were allowed to accumulate in the interstitial space, interstitial colloid osmotic pressure would increase. This would result in increased forces favoring filtration into the interstitial fluid, which would soon cause massive interstitial edema. Death of the individual could occur from circulatory collapse.

The second essential role played by the lymph system involves the absorption of fats from the small intestine. In the small intestine, fats and fat-soluble vitamins are absorbed into small lymph vessels called lacteals, and are then delivered to the general circulation. Fat and the fat-soluble vitamins are required for life.

The third essential role played by the lymph system involves immune function. Because of the high permeability of the lymph capillaries, bacteria and other microorganisms enter the lymph system from infected areas and are transported to and through lymph nodes, where they become trapped and removed from the circulation. Lymph nodes are an intertwining meshwork of vessels filled with tissue macrophages and T and B cells; bringing bacteria and other cellular debris to the lymph nodes allows the immune and inflammatory cells an opportunity to protect the host from widespread infection. Lymph nodes are spaced intermittently along the lymph vessels.

The electrocardiogram (ECG) is the measurement of the electrical currents of the heart. Contraction of the atria and ventricles results from action potentials occurring simultaneously in all muscle cells of the atria, followed by all muscle cells of the ventricles. Electrodes placed in specific locations on the body can
detect these action potential currents. The currents can then be graphically displayed and interpreted.

When cardiac muscle cells die during a myocardial infarct (MI), they release their intracellular contents. Specific proteins and enzymes normally present only inside cardiac cells can be measured in the blood. This allows one to accurately diagnose the existence and frequently the extent of myocardial cell death. Because different enzyme levels are elevated at different times after infarction, the timing of the infarct can be determined.

Proteins released after injury to the myocardial cells include myoglobin, normally found only in skeletal and cardiac muscle cells, and the cardiac-specific contractile proteins, troponin T, C, and I. Highly sensitive bedside laboratory kits, capable of measuring the presence of very low amounts of serum troponin T and I within a short time of a suspected infarct, have the capacity to revolutionize early detection of an MI. Because troponin T elevates early and stays elevated for up to two weeks, it is useful for diagnosing cardiac events that may have occurred in the past 14 days. C-reactive protein is also released in the presence of myocardial injury. Myocardial creatine kinase (CK-MB) is an enzyme that is released with cardiac cell death. Lactic acid dehydrogenase (LDH), and serum glutamic oxaloacetic transaminase (SGOT) may also be elevated after myocardial injury, but are no longer considered the best indicators. The plasma concentration of each of these enzymes and proteins varies depending on the time since injury and the extent of the cell damage. Table 13-2 summarizes the most definitive serum markers of myocardial ischemia.

Cardiac stress testing involves having an individual exercise up to his or her maximal capacity while observers monitor physical symptoms and the ECG. In a simple exercise stress test, the patient is asked to either walk on a treadmill or ride an exercise bike. The pattern of the ECG is observed for alterations in rhythm, the presence of AV blocks, and evidence of ST-segment changes indicative of hypoxia. Onset of physical symptoms, such as chest pain and extreme shortness of breath, is monitored.