Phys Ch 21
Blood Flow Regulation in Skeletal Muscle at Rest and During Exercise
 Blood flow through skeletal muscle can increase 25-50x in a well-trained athlete during strenuous exercise
 During rhythmic exercise (such as running), blood flow increases and decreases with each muscle contraction –
at end of exercise, blood flow remains high for a few seconds, then returns to normal over the next couple of
minutes
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Cause of lower blood flow during exercise is compression of blood vessels by contracted muscle – during
strong tetanic contraction, blood flow can almost be stopped
During rest, some muscle capillaries have little or no blood flowing, but during strenuous exercise, all capillaries
open – diminishes distance oxygen and other nutrients must diffuse from capillaries to contracting muscle fibers
and contributes to increased capillary surface area
Increase in muscle blood flow during exercise mainly caused by vasodilation of arteries mainly caused by the fact
that the muscles are using oxygen, decreasing oxygen in tissue fluids, which in turn causes lack of oxygen in
arteries (lack of oxygen releases vasodilator substances)
o Adenosine can partially increase blood flow to skeletal muscle, but not to same extent as natural
exercise and cannot sustain vasodilation
o Vasodilator effects maintained after adenosine has given out by K+, ATP, lactic acid, and CO2
Skeletal muscles have SNS vasoconstrictor nerves that secrete norepinephrine at their nerve endings – can
decrease blood flow through resting muscles to as little as ½ normal
o Mechanism important in circulatory shock and during other periods of stress when necessary to
maintain high blood pressure
o Adrenal medullae also secrete epinephrine, which has a slight vasodilator effect because it excites betaadrenergic receptor of vessels
Three major effects essential for circulatory system to supply blood during exercise
o Mass discharge of SNS throughout body with consequent stimulatory effects on circulation in entire
body
o Increase in arterial pressure
o Increase in cardiac output
At onset of exercise, signals transmitted to vasomotor center to initiate SNS discharge throughout body,
simultaneously inhibiting PNS signals to heart
o Heart stimulated to greatly increased heart rate and increased pumping strength
o Most of arterioles of peripheral circulation strongly contracted, except for arterioles in active muscles,
which are strongly vasodilated by local vasoldilator effects
 Coronary and cerebral circulatory systems have poor vasoconstrictor innervation, so they are
not in the systems that experience vasoconstriction
o Muscle walls of veins and other capacitative areas of circulation contracted powerfully, increases mean
systemic filling pressure, increasing cardiac output
Combined efforts of SNS stimulation increase arterial blood pressure (especially in vasoconstricted areas)
o Extra pressure stretches walls of vessels, allowing increase of blood flow
SNS response still occurs everywhere in body, even if person is using only a few muscles during exercise (but
under tense conditions)
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increased cardiac output curve during exercise results from SNS stimulation of heart
Black lines are normal circulation
Red lines are under heavy exercise
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Venous return curve increase comes from
 Mean systemic filling pressure rising tremendously at onset of exercise
 SNS stimulation contracts veins and other parts of circulation
 Tensing of abdominal and other skeletal muscles compresses many internal vessels,
providing more compression of entire vascular system
 Slope of venous return curve rotates upward – caused by decreased resisitance in virtually all
blood vessels in active muscle tissue, which causes resistance to venous return decrease,
increasing upward slope of venous return curve
o Note right atrial pressure doesn’t really change (if anything, it might drop some in a well-conditioned
athlete because of greatly increased SNS stimulation of heart)
Coronary Circulation
 Almost 1/3 of deaths in industrialized countries from coronary artery disease, and almost all elderly people have
at least some impairment of coronary artery circulation
 90% of heart muscles supplied by coronary vasculature
 Very small amount of coronary venous blood flows back into heart through very small thebesian veins, which
empty directly into all chambers of heart
 During strenuous exercise, heart in young adult increases cardiac output 4-7x, pumping blood against a higher
than normal arterial pressure – increases work output of heart 6-9x
o Coronary blood flow increases 3-4x to supply extra nutrients needed by heart
o Efficiency of heart utilization of energy increases to make up for relative deficiency of coronary blood
supply
 Capillary blood flow in left ventricle falls to low value during systole because of strong compression of left
ventricular muscle
o During diastole, cardiac muscle relaxes and no longer obstructs blood flow through left ventricular
muscle capillaries, resulting in rapid blood flow throughout diastole (huge spike as soon as systole ends
because of releasing pent-up pressure)
o Right ventricular capillaries act much as left ventricular capillaries, except nowhere near as dramatic
because of lesser contraction of right ventricle
 During systole, blood flow through subendocardial plexus of left ventricle is reduced (extra vessels of
subendocardial plexus normally compensate for this)
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Coronary blood flow increases almost in direct proportion to any additional metabolic consumption of oxygen
by heart – exact mechanism not known
o Adenosine from ATP is involved (also K+, H+, CO2, prostaglandins, and NO)
Direct effects from nervous system on coronary vasculature – acetylcholine from vagus nerves and
norepinephrine and epinephrine from SNS nerves on coronary vessels themselves
o Acetylcholine has direct effect to dilate coronary arteries
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Indirect effects from nervous system on coronary vasculature – secondary changes caused by increased or
decreased activity of heart
o Play far more important role in normal control of coronary blood flow
o Increased metabolism of heart sets off local blood flow regulatory mechanisms for dilating coronary
vessels, and blood flow increases in proportion to metabolic needs
o Acetylcholine slows heart and has slight depressive effect on heart contractility, decreasing cardiac
oxygen consumption and therefore indirectly constricting coronary arteries
 Much more extensive SNS innervation of coronary vessel – coronary vessels have both
o Alpha receptors – constrictor receptors in vessel wall
o Beta receptors – dilator receptors in vessel wall
 Epicardial coronary vessels have more alpha receptors, and intramuscular arteries have more beta receptors
o SNS stimulation mostly causes slight constriction
o Those with alpha vasoconstrictor effects disproportionately severe have vasospastic myocardial
ischemia during periods of excess SNS drive, usually leading to angina
Cardiac Muscle Metabolism
 Metabolic factors, especially myocardial oxygen consumption, are major controllers of myocardial blood flow
o Metabolic control can override direct coronary nervous effects within seconds if nervous stimulation
alters coronary blood flow in wrong direction
 Under resting conditions, cardiac muscle normally consumes fatty acids to supply most of its energy (70%)
o Under anaerobic or ischemic conditions, cardiac metabolism must use anaerobic glycolysis mechanisms
for energy (forms large amounts of lactic acid in cardiac tissue and most probable source of pain)
 More than 95% of metabolic energy liberated from foods used to form ATP in mitochondria
o In severe coronary ischemia, ATP degrades first to ADP, then to AMP, then adenosine – because cardiac
muscle PM is slightly permeable to adenosine, much of this can diffuse into circulating blood
o Released adenosine is one substance that causes dilation of coronary arterioles during coronary hypoxia
o In as little as 30 minutes from myocardial infarct, ½ of adenosine base can be lost from affected cardiac
muscle cells – loss can be replaced by new synthesis of adenine at 2%/hour rate
 Because of this, if more serious coronary ischemia occurs for 30 or more minutes, relief of
ischemia may be too late to prevent injury and death of cardiac cells – one of major causes of
cardiac cellular death during myocardial ischemia
Ischemic Heart Disease
 Most common cause of death in Western culture is ischemic heart disease (35% of people in US)
 Most frequent cause of diminished coronary blood flow is atherosclerosis
o Large quantities of cholesterol gradually become deposited beneath endothelium at many points in
arteries throughout body – areas of deposit invaded by fibrous tissue and frequently become calcified,
resulting in atherosclerotic plaques that protrude into vessel lumens
o Common site for development is first few centimeters of major coronary arteries
 Acute occlusion of coronary artery most frequently occurs in person who already has underlying atherosclerotic
coronary heart disease (almost never in a person with normal circulatory circulation)
o Can result from thrombus created as an effect of atherosclerotic plaque (where plaque has broken
through endothelium, coming in direct contact with blood flow)
 Because it is not a smooth surface, fibrin deposited and RBCs become entrapped to form blood
clot that grows until it occludes vessel or breaks away from attachment and flow to more
peripheral branch of coronary arterial tree and blocks a smaller artery
 Above mechanism called coronary embolus
o Local muscular spasm of coronary artery can occur as a result of direct irritation of smooth muscle by
edges of arteriosclerotic plaque or from local nervous reflexes that cause excess coronary vascular wall
contraction – may lead to secondary thrombosis of vessel
 There are almost no large communications among larger coronary arteries, but many anastomoses exist along
smaller arteries – when sudden occlusion occurs in a larger coronary artery, small anastomoses begin to dilate
within seconds, but blood flow is usually less than ½ needed to keep cardiac muscle alive
o Collateral vessels do not enlarge much more for next 8-24 hours, but then collateral flow begins to
increase, doubling by 2nd or 3rd day and reaching normal or almost normal coronary flow within a month
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People with atherosclerosis may never experience an acute episode of cardiac dysfunction, but eventually,
sclerotic process develops beyond limits of collateral blood supply to provide needed blood flow, and sometimes
collateral blood vessels themselves develop atherosclerosis
o Then heart muscle becomes severely limited in work output to the point where it can’t pump normally
required amounts of blood flow
o One of the most common causes of cardiac failure that occurs in older people
Infarction – area of muscle that has zero blood flow or so little flow that it cannot sustain cardiac muscle
function – when this happens in the heart, it’s a myocardial infarction
o Soon after onset of infarction, small amounts of collateral blood begin to seep into infarcted area, and
this, combined with progressive dilation of local blood vessels, causes area to become overfilled with
stagnant blood
o Infarcted area takes on a bluish-brown hue because all blood pooling there is deoxygenated
o Blood vessels of area appear engorged due to lack of ability to flow through the area
o In later stages, vessel walls become highly permeable and leak fluid, so muscle tissue becomes
edematous and cardiac muscle cells swell because of diminished cellular metabolism
o Cardiac muscle only needs 70-85% of the blood it usually gets to function normally
Subendocardial infarction – subendocardial muscle becomes infarcted even when there is no evidence of
infarction in outer surface portions of heart because subendocardial muscle has extra difficulty obtaining
adequate blood flow because blood vessels in subendocardium are intensely compressed by systolic contraction
o Any condition that compromises blood flow to any area of heart usually causes damage first in
subendocardial regions, and then damage spreads toward epicardium
Most common causes of death after acute myocardial infarction are decreased cardiac output, damming of
blood in pulmonary blood vessels (death from pulmonary edema), fibrillation of heart, and occasionally rupture
of heart
o Decreased cardiac output – overall pumping strength of infarcted heart is often decreased by systolic
stretch (when normal portions of ventricular muscle contract, ischemic portion of muscle is forced
outward by pressure that develops inside ventricle, causing pumping force to be dissipated over bulging
area of nonfunctional cardiac muscle)
 All of the above contribute to coronary shock, cardiogenic shock, cardiac shock, low cardiac
output failure (all synonymous with each other)
 Cardiac shock almost always occurs when more than 40% of left ventricle is infarcted, and death
occurs in over 70% of patients once they develop cardiac shock
o Damming of blood in body’s venous system – when blood is not being pumped through an area, it must
be damming somewhere – leads to increased capillary pressures, particularly in lungs
 Damming of blood in veins causes little difficulty in first few hours after MI, but symptoms
develop a few days later because acutely diminished cardiac output leads to diminished blood
flow to kidneys, which then fail to excrete enough urine, which adds progressively to total blood
volume and therefore leads to congestive symptoms
 Patients with heart failure can be asymptomatic until suddenly developing acute pulmonary
edema, which they could easily die in a few hours of presentation from
o V fib after MI – 2 especially dangerous periods after coronary infarction during which fibrillation is most
likely to occur: first 10 minutes after infarction occurs and about an hour later (this danger zone lasts for
a few hours) – fibrillation can occur several days after infarct but less likely so
 4 factors that contribute to tendency for fibrillation
 Acute loss of blood supply to cardiac muscle causes rapid depletion of K+ from ischemic
musculature, increasing K+ concentration in extracellular fluids surrounding cardiac
muscle fibers (with increased K+, cardiac musculature’s irritability is increased, and thus,
likelihood of fibrillating)
 Ischemia causes “injury current” (ischemic musculature cannot completely repolarize its
membranes after a heartbeat, so external surface of muscle remains negative with
respect to normal cardiac muscle membrane potential elsewhere in heart, so electric
current flows from this ischemic area to normal area and can elicit abnormal impulses
that can cause fibrillation)
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Powerful SNS reflexes develop after massive infarction, principally because heart does
not pump adequate volume of blood into arterial tree, leading to reduced blood
pressure – SNS stimulation increases irritability of heart, predisposing it to fibrillation
 Cardiac muscle weakness caused by MI often causes ventricle to dilate excessively,
increasing pathway length for impulse conduction in heart and frequently causes
abnormal conduction pathways all the way around the infarcted area – both predispose
heart to circus movement (excess prolongation of conduction pathways allows impulses
to reenter muscle already recovering from refractory period)
o Rupture of Infarcted area – during first day or so after infarct, there is little danger of rupture, but a few
days later, dead muscle fibers begin to degenerate, and heart wall becomes stretched thin – dead
muscle begins to bulge outward with each contraction, and systolic stretch worsens until heart ruptures
 Ventricle rupture causes rapid development of cardiac tamponade, constricting whole heart,
and patient dies of decreased cardiac output
Usually gradients of ischemia around area that is actually occluded (dead area in center surrounded by area
contracting weakly because of mild ischemia)
Shortly after occlusion, muscle fibers in center of ischemic area die – this area of dead fibers becomes bigger
because many marginal fibers succumb to prolonged ischemia
o Because of enlargement of collateral arterial channels supplying outer rim of infarcted area, much of
nonfunctional muscle recovers
o After a few days to 3 weeks, most of nonfunctional muscle becomes functional again or dies
o Fibrous tissue begins developing in dead fibers (ischemia can stimulate growth of fibroblasts and
promote development of greater than normal quantities of fibrous tissue)
o Dead muscle tissue gradually replaced by fibrous tissue
o Fibrous tissue undergoes progressive contraction and dissolution, and fibrous scar may grow smaller
over period of several months to a year
o Normal areas of heart gradually hypertrophy to compensate at least partially for lost dead cardiac
musculature, so heart recovers almost completely within a few months
Degree of cellular death determined by degree of ischemia and workload on heart muscle
o Anastomotic blood vessels that supply blood to ischemic areas of heart must also still supply areas of
heart they normally supply
o Large vessels become dilated during stress, allowing most of blood flowing into coronary vessels to flow
through normal muscle tissue, leaving little blood to flow through small anastomotic channels into
ischemic area (coronary steal syndrome)
Angina pectoris begins to appear whenever load on heart becomes too great in relation to available coronary
blood flow – often referred to left arm, left shoulder, left side of neck, and sometimes left side of face
o Most people with chronic angina due to stress, pain is because of sympathetic vasoconstrictor nerve
signals
o Angina exacerbated by cold temperatures or having a full stomach, both of which increase workload on
heart
o Pain frequently described as hot, pressing, and constricting
o Vasodilators can give immediate relief of pain (nitroglycerin and other nitrate drugs) – can use
angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and
ranolazine
o Can also be treated with beta blockers such as propranolol – blocks SNS beta-adrenergic receptors,
which prevents SNS enhancement of heart rate and cardiac metabolism during exercise or stress
Aortic-coronary bypass surgery – removing subcutaneous vein from arm or leg and grafting this vein from root
of aorta to side of peripheral coronary artery beyond atherosclerotic blockage point
Coronary angioplasty – small balloon-tipped catheter passed into coronary system and pushed through partially
occluded artery until balloon straddles partially occluded point; balloon inflated, which markedly stretches
diseased artery
o Small stainless steel mesh tubes (stents) sometimes placed inside coronary artery dilated by angioplasty
to hold artery open – endothelium usually grows over it in a few weeks, allowing blood to flow smoothly
through stent
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Restenosis of blocked coronary artery occurs in 25-40% of patients treated with angioplasty, often
within 6 months of initial procedure, due to excessive formation of scar tissue that develops underneath
healthy new endothelium that has grown over stent
Drug-eluting stents (slowly release drugs) can prevent excessive growth of scar tissue