Physiology: Chapter 21 - Muscle Blood Flow and Cardiac Output During Exercise; the Coronary Circulation and Ischemic Heart Disease

What percentage of total cardiac output accounts for normal coronary blood flow?

4-5%

What percentage of oxygen in coronary arterial blood is removed as blood flows through heart muscle normally?

70%

Which two systems have poor vasoconstrictor innervation?

coronary system cerebral system these are unaffected by mass sympathetic discharge during exercise and do not vasoconstrict

When is blood flow decreased: during contractions or between contractions?

during contractions this occurs because contracted muscle compresses the blood vessels

How do the capillaries of muscles change from rest to exercise conditions?

during rest, some capillaries have little to no flowing blood during strenuous exercise, all capillaries open this may contribute to a twofold to threefold increased capillary surface area

During systole, how does the blood flow through the subendocardial plexus of the left ventricle change?

during systole: blood flow through subendocardial arteries is REDUCED this is caused by LV contraction compressing the intramuscular arteries extra vessels of the subendocardial plexus normally compensate for this reduction in blood flow

Why do dormant capillaries of muscle open during strenuous exercise?

it diminishes the distance that O2 + nutrients must travel (diffuse) from capillaries to tissue (muscle fibers)

What supplies the lateral portion of the left ventricle?

left coronary LCA: A+L RCA: R+P

What mainly supplies the anterior and lateral portions of the left ventricle?

left coronary artery

What is the main regulation mechanism of blood flow through the coronary system?

local arteriolar vasodilation in response to nutritional needs of cardiac muscle

What causes the tremendous increase in blood flow during skeletal muscle activity?

local regulation: chemicals acting directly on the muscle arterioles to cause dilation triggered by OXYGEN DEPLETION (as the muscles are active, they are using O2 rapidly)

What is the major cause of cardiac cellular death during myocardial ischemia?

loss of adenosine --> loss of adenine base (new synthesis is not fast enough to replace lost)

What chemical plays a major role in regulating blood flow in the coronary arteries?

oxygen

What is a situation where blood flow can almost be stopped due to muscle contraction?

strong tetanic contraction - sustained compression of the blood vessels

Any condition that compromises blood flow to any area of the heart usually damages which regions first?

subendocardial regions spreads toward the epicardium this initial damage to subendocardial region is because of compression of blood flow due to systolic contraction of the heart

What drugs are used in the treatment/relief of chronic, stable (exercise) angina pectoris?

vasodilators: -nitrates -short-acting NTG -ACE inhibitors -ARBs -calcium channel blockers -ranolazine -beta blockers

venous blood from which region of the heart flows though the coronary sinus, back to the right atrium?

venous blood from left ventricular muscle this accounts for 75% of coronary blood flow

What is one of the most stressful conditions that the normal circulatory system faces?

very strenuous exercise

Why does the local muscle tissue become edematous in the later stages of MI?

vessel walls become highly permeable and leak fluid also, cardiac muscle cells begin to swell (diminished cell metabolism)

Alpha receptors in the blood vessel walls are _______ receptors

constrictor *AC* BD

Increased arterial pressure is the result of what?

*increased sympathetic stimulation, which causes: -vasoconstriction of arterioles/small arteries in most tissues of the body (except active muscles, cerebral and coronary systems) -increased pumping activity by the heart -increased mean systemic filling pressure (due to increased venous contraction/return)

What is the timeline of myocardial recovery following a large myocardial infarction(MI)?

*partially or almost completely recovered within a few months post MI* 1. occlusion 2. center muscle fibers die (in ischemic area) 3. dead fibers become bigger -many marginal fibers die due to prolonged ischemia 4. at same time of marginal fiber death, enlargement of collateral circulation supplies and recovers the non-functional regions of ischemic area 5. few days to 3 weeks: most nonfunctional muscle becomes functional or dies (one or the other) 6. same time: fibrous tissue develops among dead fibers -ischemia stimulates fibroblast growth and production of excess fibrotic tissue 7. dead muscle tissue gradually replaced by fibrous tissue -fibrous tissue undergoes progressive contraction/dissolution -fibrous scar becomes smaller (months-1 year) 8. normal areas of heart *hypertrophy* to compensate

What is the average rate of blood flow through skeletal muscle at rest?

3-4 mL/min per 100g of muscle

the indirect effects are mostly ________ to the direct effects in normal control of coronary blood flow

opposite

What are the 3 results of sympathetic discharge (during exercise) on the circulatory system?

1. *Heart rate & contractility increase* (sympathetic stim/parasym inhibition) 2. *Peripheral circulation undergoes strong contraction EXCEPT arterioles in the active muscles* -arterioles in active muscle dilate due to low O2/local chemicals -peripheral circulation "lends" blood supply to active muscle -spares coronary and cerebral systems 3. *powerful vasoconstriction of veins and capacitance vessels* -increases mean systemic filling pressure -increased venous return of blood to heart -increased CO

What two factors contribute to the overall increase in cardiac output with exercise?

1. *Increased cardiac output* -sympathetic stimulation causing increased HR and increased contractility 2. *Decreased resistance to venous return* -mean systemic filling pressure rises bc of contraction of veins (sympathetics) and contraction of abdominal muscles (compresses internal vessels) -slope of venous return curve rotates upward due to *decreased resistance* in all blood vessels in active muscle tissue

What two events occur when oxygen concentration in tissue fluids of active skeletal muscle begins to decrease?

1. *local arteriolar vasodilation* -absence of O2 - cannot maintain contraction (tone) 2. (release of vasodilator substances* -adenosine (may be most important) -potassium ions -ATP -lactic acid -CO2

What three major effects occur during exercise that are essential for the circulatory system to provide increased blood flow to the muscles that require it?

1. Mass Discharge of Sympathetic NS 2. Increase in Arterial Pressure 3. Increase in Cardiac Output

in addition to local tissue vasodilator mechanisms, what role does the nervous system play in controlling blood flow?

1. Sympathetic vasoconstrictor nerve fibers -release NE at nerve endings -important in circulatory shock and other periods of stress 2. Adrenal medulla -secretes NE and E into blood *during exercise* -NE = vasoconstriction via alpha receptors -E = vasodilation via beta receptors

What are the 4 most common causes of death after acute MI?

1. decreased CO -systolic stretch -cardiac shock 2. pulmonary edema 3. fibrillation 4. rupture of the heart -cardiac tamponade

What are 4 factors that contribute to the tendency for heart to fibrillate?

1. depletion of K+ inside myocardial cells/*increase K+ in EC fluids surrounding myocardial cells* -increases irritability of cardiac musculature 2. *injury current* -ischemic musculature does not completely repolarize membrane after heartbeat (remains negative) -current flows from ischemic area to normal area -elicit abnormal impulses causing fibrillation 3. *Sympathetic reflexes* -reduced cardiac output/reduced BP leads to sympathetic stimulation 4. *dilation of ventricles* -caused by cardiac muscle weakness -dilation of ventricles increases the pathway length for impulse conduction to travel -circus movements -excess prolongation of conduction pathways causing already repolarizing muscle to receive impulse

What are the 2 danger periods in which fibrillation is most likely to occur following coronary infarction?

1. during the *first 10 minutes* ---safety period--- 2. 1 hour later, lasting for another few hours

What 2 factors contribute to infarcted areas of myocardium becoming overfilled with stagnant blood?

1. small amounts of collateral blood seep into infarcted area 2. progressive dilation of local blood vessels (response to low O2)

What are 2 causes of acute occlusion in the context of atherosclerosis of the coronary vessels?

1. thrombus formation -coronary embolus 2. local muscular spasm -secondary thrombosis

How does the rate of blood flow through skeletal muscle change during extreme, strenuous exercise?

25- to 50-fold (from 3-4 to 100-200 mL/min per 100g of muscle) can go as high as 400mL/min in thighs of endurance-trained athletes

What is the mechanism behind myocardial ischemia leading to cardiac cell death?

ATP - produced in the mitochondria; acts to provide energy for muscle contraction with severe coronary ischemia, ATP degrades --> ADP --> AMP --> adenosine myocardial cell membrane slightly permeable to adenosine --> leaks out into tissue fluids dilation of coronary arterioles (during coronary hypoxia) LOSS OF ADENOSINE IS SERIOUS: -within 30 min of coronary ischemia, one half of the adenine base can be lost from the affected cardiac cells -loss of adenine base is replaced with synthesis of new adenine at a rate of only 2% per hour -relief of ischemia may be too late to prevent injury/death of cells

Coronary vessels are more extensively innervated by which autonomic system?

SYMPATHETIC

under ischemic conditions, what type of metabolism does cardiac muscle use to supply energy?

anerobic glycolysis results in a large amount of lactic acid formation most likely a cause of cardiac pain in cardiac ischemic conditions

What does the left coronary artery mainly supply?

anterior and lateral portions of the LV

Coronary blood flow increases almost in direct proportion to what?

any additional metabolic consumption of *oxygen* by the heart

How is the sympathetic system activated during exercise?

at the same time signals are transmitted from the brain to skeletal muscle (to cause skeletal muscle contraction), *signals are also sent to the vasomotor center* at the same time, parasympathetic signals to the heart are inhibited

What is the most frequent cause of diminished coronary blood flow?

atherosclerosis

What are some substances that are thought to cause the pain associated with ischemic cardiac muscle?

acidic substances such as lactic acid histamine kinins proteolytic enzymes

What form of adenosine (ATP, ADP, AMP, adenosine, or adenine base) is the cardiac muscle cell membrane slightly permeable to?

adenosine

What substance(s) are released that cause coronary vasodilation?

adenosine adensosine phosphate compounds K+ ions H+ ions CO2 prostaglandins Nitric Oxide (NO)

Which receptors are predominant in epicardial coronary vessels (alpha or beta)?

alpha - constrict - epi

What is the basic mechanism behind development of a thrombus in atherosclerosis?

atherosclerotic plaque broken through endothelium --> direct contact with blood (unsmooth surface) --> platelet adherence --> fibrin deposit --> red blood cell entrapment, forming a blood clot --> growth until occlusion of the vessel lumen occurs -------- clot may break away from attachment to plaque and flow more distally: *coronary embolus*

Where are subendocardial arteries found?

beneath the endocardium

Which receptors (alpha or beta) are predominant in the intramuscular arteries of cardiac muscle?

beta beta -dilate -intramuscular

How do beta blockers help relieve angina pectoris occurrence?

blocks beta-adrenergic receptors of the heart --> sympathetic this prevents increased heart rate/metabolism during exercise or emotional episodes

During strenuous exercise, what accounts for the discrepancy in increased coronary blood flow vs. increased workload?

cardiac utilization of energy increases (efficiency of using energy) to make up for the relative deficiency of coronary blood supply --> RATIO OF ENERGY EXPENDITURE by the heart to coronary blood flow increases energy expended by heart:coronary blood flow ^^^^this ratio increases the efficiency of cardiac utilization of energy increases

When the area of ischemia is large, what does the area look like (what type of cells found)?

central area of dead fibers --> immediately surrounded by non-functional cells --> surrounded by an area of weakly contracting cells

What is angina pectoris?

chest/cardiac pain that occurs whenever load on heart becomes too great in relation to available coronary blood flow usually felt beneath upper sternum over heart sometimes referred to distant surface areas of body, most commonly: -left arm -left shoulder -sometimes to neck/side of face can also be exacerbated by cold temperatures or by having a full stomach (both events increase workload of heart) pain lasts for a few minutes described as "hot, pressing, constrictive"

The degree of damage to the heard muscle caused by slow-developing atherosclerotic constriction or sudden coronary occlusion is determined by the degree of ____________ ___________

collateral circulation

when atherosclerosis constricts the coronary arteries slowly (not an acute occlusion), what is the role of collateral circulation?

collateral vessels can develop at the same time while atherosclerosis develops -may never experience acute episodes of cardiac dysfunction at this phase- eventually, sclerotic process develops beyond the limits of collateral blood supply (may even develop plaques themselves) heart muscle becomes severely limited in work output --> cardiac failure

What is the mechanism of death due to pulmonary edema?

decreased cardiac output --> damming of blood in atria/systemic circulation initially causes little symptoms. what happens is that this damming of blood in the atria decreases renal blood flow --> decreased urine output --> increased total blood volume --> congestive symptoms develop after first few days after onset of heart failure sudden development of acute pulmonary edema death within a few hours after appearance of initial pulm symptoms

Beta receptors in the blood vessel walls are ______ receptors

dilator receptors AC *BD*

What is the effect of ACh on coronary arteries?

direct effect to dilate the coronary arteries (but distribution of vagal nerve fibers to ventricular coronary system is not very great)

What are direct effects on coronary blood flow via autonomic stimulation? What are the indirect effects? How are these two effects related?

direct effects: -vagus nerves release ACh (parasym) -sympathetic nerves release NE and E indirect effects: -vasoconstriction -vasodilation --------------- parasympathetic direct stimulation to the heart causes a depressive effect --> decreases cardiac oxygen consumption --> indirect vasoconstriction of coronary arteries --> decreased blood flow ---------- sympathetic direct stimulation to the heart --> increased heart rate and contractility --> increased metabolism --> increased oxygen demand/decreased oxygen concentration --> vasodilation of the coronary arteries --> increased blood flow

What is the cause of local muscular spasm of a coronary artery?

direct irritation of the smooth muscle of the arterial wall by the edges of an atherosclerotic plaque OR local nervous reflexes, causing excess coronary vascular wall contraction --> may lead to secondary thrombosis

what can cause vasospastic myocardial ischemia, with resulting angina?

disproportionately severe alpha vasoconstrictor effects during periods of excess sympathetic drive

What arteries supply most of cardiac muscle?

epicardial coronary arteries on the OUTER SURFACE

Under resting conditions, what is the major supply of energy in cardiac muscle?

fatty acid (70%)

When does an acutely infarcted area typically rupture?

few days post-infarct (not first day or so)

What causes the heart to rupture at an infarcted area?

few days post-infarct, the dead cells begin to degenerate heart wall becomes thinly stretched dead muscle bulges outward - systolic stretch becomes greater and greater heart eventually ruptures loss of blood into pericardial space --> *CARDIAC TAMPONADE*

What is a common site for development of atherosclerotic plaques?

first few centimeters of the major coronary arteries

How is the pressure in the right atrium changed during exercise?

hardly changed in a person with a very strong heart, the right atrial pressure falls below normal in very heavy exercise bc of greatly increased sympathetic stimulation of the heart

What is meant by the term "infarcted"?

immediately after acute coronary occlusion, blood flow ceases beyond occlusion except small amounts of collateral flow amount of muscle that has either ZERO FLOW or so LITTLE FLOW that it cannot sustain cardiac function = infarcted "myocardial infarction"

what is coronary steal syndrome

in a patient who has MI, when the workload of the heart is greatly increased (i.e. during exercise), the normal areas of the heart still need increased blood flow dilation of the vessels of normal musculature this allows most of the blood flowing into the coronary vessels to flow through the normal tissue --> little blood to flow through the small anastomotic channels into the ischemic area --> ischemic condition worsens

By what mechanism is adenosine introduced into tissue fluids of the heart muscle?

in presence of very low concentrations of oxygen in muscle cells, ATP is degraded into AMP AMP is further degraded adenosine is released into tissue fluids of the heart muscle result: increase in local coronary blood flow much is then later reabsorbed back into the cardiac cells

why is arterial pressure increase important during exercise?

increase in pressure stretches the walls of the vessels that increase in BP plus local vasodilators increases total blood flow to active muscles immensely

When the vigor of cardiac contraction increases, the rate of coronary blood flow ______________

increases as well

what plays a more important role in controlling coronary blood flow, direct or indirect effects?

indirect effects (which are in response to the direct effects on the heart)

What causes ischemic heart disease?

insufficient coronary blood flow may be: -acute (due to acute coronary occlusion or fibrillation) -progressive/slow (period of weeks/years resulting in weak pumping process over time)

What is the most common cause of death in Western culture?

ischemic heart disease

Where are the main coronary arteries located in/on the heart?

main coronary arteries lie on the surface of the heart smaller arteries penetrate from the surface into the cardiac muscle mass these arteries supply the majority of nutritive blood (only 1/10 of blood supply comes from blood directly in the cardiac chambers)

What does the right coronary supply mainly?

most of the right ventricle + posterior portion of left ventricle (80-90% of individuals)

What causes a bluish-brown hue in the infarcted area?

muscle fibers use up last of oxygen in hemoglobin result: completely deoxygenated Hb

What accounts for patients who have recovered from a large MI to have almost full functional capability but decreased pumping capability?

normal people have a "cardiac reserve" - normal heart capable of pumping 300-400% more blood per minute than the body needs during rest this is decreased to about 100% in patients with MI can still perform most normal daily activities, but not strenuous exercise (which would require increased pumping capacities)

What is cardiac tamponade?

occurs when the heart ruptures blood leaks out into the pericardium pericardium pressure increases, compressing the heart from the outside blood does not flow into right atrium patient dies suddenly of diminished CO

How does the adrenal medulla cause a vasodilating effect during exercise?

releases 20% NE and 80% Epinephrine E is a potent agonist for beta receptors (instead of alpha), and these receptors cause vasodilation NE - agonist for beta receptors

What is aortic-coronary bypass surgery?

remove section of a subcutaneous vein from arm or leg --> graft vein from root of aorta to side of a peripheral coronary artery BEYOND atherosclerotic blockage point anginal pain relieved and can expect normal survival rate (unless heart has previously been severely damaged)

What artery supplies the posterior portion of the left ventricle?

right coronary artery

Small anterior cardiac veins carry venous blood back to the right atrium from where?

right ventricular muscle

When a sudden occlusion occurs in one of the larger coronary arteries, what is the process of collateral circulation formation?

small anastomoses (of smaller arteries) begin to dilate -initially (within seconds), they dilate so that blood flow is less than half of what is needed to keep cardiac muscle alive -within 8-24 hours, not much change/enlargement occurs -collateral flow increases: doubles by second or third day -returns to normal coronary flow within 1 month

How does venous blood from the right ventricular muscle reenter the right atrium?

small anterior cardiac veins

What is coronary artery angioplasty?

small, balloon-tipped catheter (1mm in diameter) passed, pushed through the partially occluded artery until balloon portion straddles occlusion --> balloon inflated with high pressure --> stretches diseased artery --> increased blood flow 75% are relieved of symptoms following procedure for several years, but many will still need coronary bypass surgery

What are intramuscular arteries derived from (which arteries)?

smaller intramuscular arteries derived from epicardial coronary arteries

When are stents used?

stent - small, stainless steel mesh tube placed inside a coronary artery after being dilated by angioplasty to hold the artery open, preventing restenosis after a few weeks of placement of stent, endothelium grows over metal surface, allowing blood to flow smoothly through stent restenosis does occur in 25-40% of patients with angioplasty (6 months from initial procedure) -due to excessive formation of scar tissue that developed underneath healthy, new endothelium -drug-eluting stents may help prevent growth of scar tissue

What are the phasic changes that occur in coronary blood flow during systole/diastole?

systole: blood flow through coronary (LV) capillaries DECREASES -result of compression from left ventricular muscle diastole: blood flow through coronary (LV) capillaries INCREASES -result of relaxation of left ventricular muscle ----- these phasic changes are best seen in the left ventricles; occurs much less in right ventricle

When the area of ischemia is small, what type of cells typically exist? (nonfunctional or dead)

temporarily nonfunctional cells due to inadequate nutrition to support muscle contraction

What type of exercise results in a greater increase in mean arterial pressure: -exercise under tense conditions (only a few muscles used) -massive whole body exercise (large masses of active muscle)

tense conditions, where only a few muscles are being used, results in a greater increase in arterial pressure this is because more vessels are being constricted (less local vasodilation)

What do thebesian veins carry? From where - to where?

thebesian veins carry a very small amount of coronary venous blood empties directly into all chambers of the heart

Who's cardiac output must increase more than normal, a non-athlete or a well-trained athlete?

well-trained athlete: CO 6-7x normal non-athlete: 4-5x normal this is because there is a larger mass of skeletal muscle in the athlete, requiring larger amounts of blood flow to satisfy the metabolic needs of the exercising muscles

What is systolic stretch?

when an area of myocardium is infarcted, during systole (LV contraction), the ischemic portion of the muscle (dead/nonfunctional) is forced outward this dissipates the pumping force decrease in cardiac output over time, can cause peripheral ischemia --> called: -coronary shock -cardiogenic shock -cardiac shock -low cardiac output failure

When does cardiac shock almost always occur?

when more than 40 percent of the left ventricle has infarcted