Chapter 21
Muscle Blood Flow and Cardiac Output During Exercise; the Coronary Circulation and Ischemic Heart Dz
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Regulation of blood flow to skeletal muscles and coronary system mainly by local control of vascular resistance based on tissues
metabolic need
Cardiac Output Control During Exercise
 Nonathlete: cardiac output can increase 4-5X Athlete: cardiac output can increase 6-7X
 Blood flow fluctuates w/each heart contraction
o End of contractions - blood flow is high for a few secs
 Contracted muscle will compress vessels lowering flow
o Strong tetanic muscle contractions -> sustained compression of vessels -> flow almost stopped -> rapid weakening
of muscle contraction
 Rest: some capillaries have little or no blood flow, Exercise: all capillaries open 2/3X cap surface area
 Skeletal Muscle
o Chemical act directly on arterioles - dilation
o O2 is used by activated muscle, Dec. [O2] in tissue fluids -> local arteriolar vasodilation b/c contraction cannot be
maintained, and b/c O2 def may cause release vasodilator substances
o Adenosine cannot increase blood flow to same extent, and cannot sustain vasodilation for more than 2 hours
(good but not good enough)
o Maintanence of increased capillary blood flow
 Potassium ions, ATP, lactic acid, CO2
o Sympathetic Vasoconstrictor Nerves
 Fibers secrete norepinephrine at nerve endings -> decrease blood flow thru resting m's
 Adrenal medullae secrete large amounts of norepinephrine and epinephrine into circulating blood during
exercise
 Circulating norepinephrine -> vasoconstrictor effect, excites alpha vasoconstrictor receptors
 Epinephrine -> slight vasodilator effect b/c excites more of the beta-adrenergic receptors of vessels
(vasodilator receptors)
o Major effects during exercise
 Mass discharge of SNS
 Signals from brain to muscle sand vasomotor center to initiate sym discharge
 Simultaneously parasym signals to heart are reduced
 Heart is stim to increase HR and Inc. pumping strength
 Most arterioles of peripheral circulation are strongly contracted
a. Active muscle arterioles are dilated
b. Heart stim to supply Inc. flow (2L/min of extra blood flow to muscles)
c. Coronary/cerebral systems have poor vasoconstrictor innervation, are spared
 Muscle walls of veins/capacitative areas are contracted -> Inc. the mean systemic filling pressure ->
promotes venous return -> Inc. cardiac output
 Inc. in arterial pressure
 Inc. sym stim -> Inc. arterial pressure
 Vasoconstriction of arterioles and small arteries (except in active muscle)
 Inc. pumping of heart
 Inc. in mean systemic filing pressure caused by venous contraction
 Inc. pressure can be 20-80mmHg
 Exercise under tense conditions using few muscle still cause total body sym stim, mean arterial
pressure can be as high as 170mmHg
 Exercise using whole body Inc. pressure often only 20-40mmHg b/c of extreme vasodilation is large
masses of active muscle
 Muscle stimulation in lab -> 8X normal blood flow
 Real life: Raise in arterial pressure, vessel wall stretch, locally released vasodilators -> higher
BP -> can increase total flow to 20X normal
 Inc. in cardiac output
 Cardiac output Inc. in order to supply skeletal muscles w/O2 and nutrients required for the Inc.
activity
 Sym stim causes Inc. HR and increased strength of contraction (often 2X normal) -> w/o this cardiac
output Inc. would be limited to plateau level of the normal heart (2.5 fold vs. 4 fold untrained runner
vs. 7 fold marathon runner) Damn!
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Two important changes
 Mean systemic filling pressure rises at onset of heavy exercise
 Sym stim contracts veins
 Abd tenses -> more compression of entire capacitative vascular system -> greater Inc. in
mean systemic filling pressure from 7 to 30mmHg
 Slope of the venous return curve rotates upward
 Dec. resistance in all vessels in active muscle
 Resistance to venous return Dec.
 Inc. the upward slope of venous return curve
Strong hearts - R atrial pressure often falls below normal in heavy exercise b/c Inc. sym stim of heart
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Coronary Circulation
 L coronary artery supplies anterior and L lateral portions of L ventricle
 R coronary artery supplies most of R ventricle and posterior part of L ventricle
 Coronary sinus - most coronary venous blood from L ventricular muscle, empties into R atrium (75% of total coronary
blood flow)
o Venous blood from R vent muscle returns to R atrium thru small anterior cardiac veins
o Small amount of venous blood flows back into heart thru thebesian veins (very minute) - empty into all heart
chambers
 Resting coronary blood flow = 70ml/min/100g heart weight (225ml/min) ~ 4-5% total cardiac output
 Strenuous exercise
o cardiac output Inc. 4-7fold
o work output Inc. 6-9 fold
o coronary blood flow Inc. 3-4fold (supply extra nutrients)
 Coronary cap blood flow in L ventricular muscle
o Systole: falls to low value -> cap constricted
o Diastole: raises to higher value -> cardiac muscle relaxes no longer obstructing flow
 Epicardial coronary arteries - outer surface, supply most of the muscle
o Smaller arteries branch off and penetrate muscle supplying nutrients
Subendocardial
arteries - plexus immediately under endocardium
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o Extra vessels can compensate for reduced flow caused by muscle contraction during systole
 Control of Flow
o Reg by local arteriolar vasodilation in response to nutritional needs
 contraction increased -> rate of flow is increased
 Contraction decreased -> rate of flow is decreased
o ~70% O2 in coronary arterial blood removed as blood flows thru heart
 Very little O2 left for heart muscle unless coronary flow Inc.
 Current theory:
 Dec. in [O2] in heart -> vasodilator substances released from muscle cells -> dilate arterioles
 Adenosine - great vasodilator
 STP degrades to AMP -> degraded to release adenosine into tissue fluids of heart
muscle -> Inc. local coronary blood flow
 Pharm agents that block/partially block vasodilator effect of adenosine doesn't prevent
coronary vasodilation caused by Inc. heart muscle activity
 Infusion of adenosine maintains vascular dilation for only 1-3 hours -> muscle activity
still dilates local blood vessels even when adenosine can't any longer
 Other vasodilators: Adenosine phosphate compounds, K+ ions, H+ ions, CO2, prostaglandins,
nitric oxide
o Nervous Control
 Direct Effects - action of nervous transmitter substances
 Acetylcholine from vagus nerves
 Released by parasym stim, dilates coronary arteries
 Norepinephrine/epinephrine from sym nerves on coronary vessels
 Either vascular constrictor or vascular dilator effects
 Depends on presence/absence of constrictor or dilator receptors in vessel walls
 Constrictor receptors = alpha receptors
 Epicardial coronary vessels
 Alpha effects can be crazy severe -> vasospastic myocardial ischemia during
periods of excess sym drive -> anginal pain
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Dilator receptors = beta receptors
 Intramuscular arteries
Indirect Effects - secondary changes in coronary blood flow (Inc./Dec. heart activity)
 More important in normal control
 Mostly opposite to direct effects
Sym stim -> release of norepinephrine/epinephrine -> Inc. in HR and heart contractility and Inc. rate of
metabolism of the heart; Inc. in metabolism -> coronary vessels dilate and blood flow Inc.
Vagal stim -> release of acetylcholine -> slows heart and depressive effect on heart contractility -> Dec.
cardiac O2 consumption & indirectly constricts coronary arteries
Metabolic factors - major controllers of myocardial blood flow
 Usually overrides nervous effects w/in sec
Metabolism
o Resting conditions: cardiac muscle consumes fatty acids (70% fatty acids) instead of carbs
o Anaerobic/ischemic conditions: anaerobic glycolysis
 Uses lots of blood glucose
 Forms lots of lactic acid in the tissue -> cardiac pain
o >95% of energy from food used to form ATP in mitochondria
o Severe coronary ischemia: ATP degrades (cardiac muscle cell membrane is permeable to adenosine) -> adenosine
diffuses from muscle cells into bloodstream
 Released adenosine -> dilation of coronary arterioles during coronary hypoxia
 Loss of adenosine -> ~1/2 adenine base can be lost w/in 30 min, synthesis at rate of 2% per hour
 after persistence of 30+ minutes injury or death of tissue can occur
---> major cause of cardiac cellular death during myocardial ischemia
Heart Attacks/Dz
 Ischemic Heart Dz
o Most common cause of death in Western culture, 35% of people in the US die of this
o Results from insufficient coronary blood flow
o Atherosclerosis - most frequent cause of diminished coronary blood flow
 People at risk
 Genetic predisposition
 Overweight or obese and sedentary lifestyle
 High blood pressure and damage to endothelial cells of coronary blood vessels
 Atherosclerotic Plaques
 Large quantities of cholesterol (chol) gradually deposit beneath endothelium of arteries
 Become invaded by fibrous tissue, frequently become calcified
 Development of atherosclerotic plaques that protrude into lumen and block/partially block blood
flow
 Common site is first few centimeters of major coronary arteries
o Acute Coronary Occlusion
 Most frequently in pts w/underlying atherosclerotic coronary heart dz, almost never in a person w/normal
coronary circulation
 Results from:
 Atherosclerotic plaque -> thrombus (local blood clot) -> occludes the artery
 Thrombus usually occurs where the plaque has broken thru the endothelium, coming in direct
contact w/flowing blood
 Plaque surface is not smooth -> blood platelets adhere, fibrin is deposited, RBCs become
entrapped to form a blood clot -> grows until it occludes
 Occasionally - clot breaks away and flows to a more peripheral point and occludes.
 Coronary embolus - thrombus that flows along the artery and occludes the vessel more
distally
 Local muscular spasm of a coronary artery
 Results from:
direct irritation of the smooth muscle by edges of a plaque
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 Local nervous reflexes -> excess coronary vascular wall contraction
 May lead to secondary thrombosis
o Collateral Circulation
 Normal heart:
 almost no large communications b/w larger coronary arteries
 Many anastomoses b/w smaller arteries
Sudden Occlusion in one of the larger arteries
 Small anastomoses dilate w/in secs - flow usually <1/2 needed
 Collateral vessels do NOT enlarge much for next 8-24 hours, but double by 2-3 day, reaching
normal/almost normal w/in 1 month
 Athrerosclerosis constricts over a period of years
 Collateral vessels can develop at the same time
 Acute episode of cardiac dysfunction may not occur
 Sclerotic process may develop beyond collateral limits or collateral vessels may develop
atherosclerosis -> work output severely limited
---> most common causes of the cardiac failure
o Myocardial Infarction
 Immediately:
 Acute coronary occlusion -> blood flow ceases in coronary vessels beyond occlusion
 Infarction - area of muscle w/zero to little flow that cannot sustain muscle function
 Soon after onset:
 Small amounts of collateral blood seep into infarcted area + progressive dilation of local blood
vessels = area overfills w/stagnant blood
 O2 is used up and hemoglobin becomes totally deoxygenated (infarcted area - bluish-brown hue, and
vessels appear engorged despite lack of flow)
 Later Stages:
 Vessel walls become highly permeable and leak fluid
 Local muscle tissue becomes edematous
 Cardiac muscle cells begin to swell, w/in a few hours of almost no blood supply -> cardiac muscle
cells die
*Cardiac muscle requires ~1.3ml of O2/100g of muscle tissue/min to remain alive
o Subendocardial Infarction
 Frequently occurs even when no evidence of infarction in outer surface portions
 Subendocardial muscle has extra difficulty getting adequate blood flow b/c vessels are intensely
compressed by systolic contraction
 Compromised blood flow usually damages first to subendocardial regions
o Causes of Death
 Decreased cardiac output
 Systolic Stretch
 Normal portions of the vent muscle contract, ischemic portion is forced outward by pressure
inside the vent
 Pumping force is dissipated by bulging area - overall pumping strength is Dec.
 Coronary shock, cardiogenic shock, cardiac shock or low cardiac output failure
 Heart becomes incapable of contracting w/sufficient force to pump enough blood into
peripheral arterial tree, cardiac failure and death of peripheral tissues
 Damming of blood in venous system
 Heart not pumping forward -> blood dams in atria, lung vessels or systemic cir.
 Little difficulty during 1st few hours after MI
 Sx develop few days later
 Acutely diminished cardiac output - diminished blood flow to kidneys
 Kidneys fail to excrete enough urine
 Adds progressively to total blood volume -> congestive symptoms
V-fib
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 Many people who die of occlusion die b/c of sudden V-fib
 Danger Periods
 1st 10 minutes after the infarction occurs
 ~ 1 hour later - lasting for a few hours
 Factors in heart beginning to fibrillate
 Acute loss of blood supply to cardiac muscle
 rapid loss of K+ from ischemic muscle
 Inc. [K+] in extracellular fluids -> irritation of cardiac musculature
 Ischemic muscle cause "injury current"
 Ischemic muscle often cannot completely repolarize its membranes
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 External surface of muscle stays negative
 Electric current flows from ischemic area to normal area
 Can elicit abnormal impulses
 Powerful sympathetic reflexes
 Heart does NOT pump an adequate volume of blood into arterials
 Leads to reduced BP
 Sym Inc. irritability of cardiac muscle
 Cardiac muscle weakness
 Causes vent to dilate excessively
 Inc. pathway length for impulse conduction in heart
 Freq causes abnormal conduction pathways around infarcted area
 Predispose development of circus movements
 Rupture of Infarcted Area
 1st day or so little risk of rupture
 Few days later -> dead muscle fibers begin to degenerate, heart wall stretched thin
 Dead muscle bulges outward w/each contraction (bigger and bigger bulge) until the heart ruptures
 When vent ruptures
 Loss of blood into pericardial space -> rapid development of cardiac tamponade (compression
of heart by blood collecting in the pericardial cavity) -> blood cannot flow into the R atrium ->
pt dies of Dec. cardiac output (oh sad!)
Stages of Recovery from Acute MI
 Damage
 Dead Area - center of large area of ischemia
 Fibers die rapidly (w/in 1-3 hours) from total loss of blood supply
 Nonfunctional Area - immediately around dead area
 Failure of contraction and usually failure of impulse conduction
 Weak Area - around nonfunctional area
 Still contracting but weakly b/c of mild ischemia
Scar
Tissue
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 Dead fiber area gets bigger b/c many marginal fibers finally succumb to prolonged ischemia (is
succumb one of those non-dirty dirty words?)
 Nonfunctional muscle (not all) recovers b/c enlargement of collateral arterial channels
 Rest of nonfunctional muscle either recovers or dies after few days to 3 weeks
 Fibrous tissue begins developing among dead fibers b/c ischemia can stim growth of fibroblast and
promote development of greater than normal quantities of fibrous tissue
(rises from the dead!!)
 Dead tissue gradually replace by fibrous tissue
 fibrous scar may grow smaller over period of several months to yr
 b/c fibrous tissue tends to undergo progressive contraction and dissolution
 Normal areas of heart gradually hypertrophy to compensate
 Rest! Because it's good for you.
 Degree of cardiac cellular death determined by degree of ischemia and workload on heart muscle
 Inc. workload (i.e. exercise, emotional strain, fatigue) - heart needs Inc. O2 and other nutrients
 Anastomotic blood vessels supplying ischemic areas must also supply their normal areas
 "Coronary steal" syndrome - Vessels dilate when heart is excessively active -> little blood left to
go thru small channels to ischemic areas
One
of the MOST important factors is tx of MI pt is absolute body rest during recovery process!
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Heart fully recovered from MI frequently permanent Dec. pumping capability below a normal heart
Pain in Coronary Heart Dz
 Ischemic cardiac muscle often causes pain sensation
 Theory: ischemia causes muscle to release acidic substances that are NOT removed rapidly enough by slow
blood flow; high [abnormal products] stim pain nerve endings
 Sensory afferent nerve fibers into CNS
Angina Pectoris - cardiac pain - progressive constriction of their coronary arteries
 Usually felt
 Beneath upper sternum over heart
 Left arm and left shoulder
 Neck, & even side of the face
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EMBRYO: heart and arms originate in the neck, both receive nerve fibers from same SC segments
Chronic Angina Pectoris
 Feel pain when exercising or experiencing emotions that Inc. heart metabolism or constrict coronary
vessels b/c sym vasoconstrictor nerve signals
 Exacerbated by cold temps or a full stomach -> Inc. heart's workload
 Pain lasts ~few minutes
 "Hot, pressing, and constricting" ---------- "It's a constricting, hot pain…."
o Drug Tx:
 Short-acting vasodilators - nitroglycerin and other nitrate drugs
 Vasodilators - angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel
blockers and ranolazine -> tx chronic stable angina pectoris
 Beta blockers - propranolol -> prolonged tx of angina pectoris
 Block sym beta-adrenergic receptors - prevents sym enhancement of HR and cardiac metabolism
o Surgical Tx - coronary artery dz
 Aortic-coronary bypass surg
 Remove a section of a subcut vein from an arm or leg
 Graft vein from the root of the aorta to the side of a peripheral coronary artery beyond the
atherosclerotic blockage
 1-5 grafts usually performed
 Anginal pain relieved in most pts
 Coronary angioplasty
 Small balloon-tipped catheter (~1mm in diameter)
 pushed thru partially occluded artery until balloon portion of the catheter straddles partially
occluded point
 balloon inflated w/high pressure -> markedly stretches the dz artery
 Blood flow thru the vessel often Inc. 3-4fold; more than 75% of pts are relieved of the coronary
ischemic symptoms for at least several years
 Small stainless steel mesh tubes called "stents" inserted to hold the artery open
 endothelium usually grows over the metal surface of the stent
 Reclosure (restenosis) occurs in ~25-40% often w/in 6mos of procedure
 usually due to excessive scar tissue formation
 Stents that slowly release drugs (drug-eluting stents) may help prevent excessive scar tissue
growth
 Laser beam!!
 Laser beam from the tip of a coronary artery catheter aimed at the atherosclerotic lesion
 dissolves lesion w/o substantially damaging the rest of the arterial wall