Tissue blood flow and exercise
•Brain
•Heart
•Muscle
BLOOD FLOW
Rate of metabolism
Control of tissue flow
• Intrinsic Control
• Extrinsic control
• Long term control
Height~ perfusion pressure
Tissue
Blood flow (ml/min/100g)
14
12
10
8
6
4
2
0
0
20
40
60
80
100 120 140 160 180
Perfusion pressure (mmHg)
Figure 20-14 Autoregulation of blood flow.
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© 2005 Elsevier
Local Control of Blood Flow
• Metabolic hypothesis: Blood flow is
governed by the metabolic activity of the
tissue. Any intervention that reduces O2
supply gives rise to the formation of
vasodilator metabolites.
• Myogenic hypothesis: The vascular
smooth muscle contracts in response to
stretch
Metabolic hypothesis
•
•
The metabolic hypothesis suggests that the
tissue releases a vasodilator;
The potential mediators of this
vasodilation are:
Adenosine
Prostaglandins
Lactate
Metabolic Hypothesis
Adenosine
cells
Smooth muscle
Smooth muscle
Arteriole
Precapillary sphincter
Capillary
Adenosine Hypothesis
 Flow  Oxygen delivery
O2 ATP ADP AMP
Adenosine vasodilation
 restore oxygen delivery
Reactive Hyperemia
Inflowing pressure (mmHg)
120
100
80
60
40
20
0
100
Blood Flow
80
60
40
20
0
0
1
2
3
4
Time (min)
5
6
7
Transmural pressure
Po
Pi
Pt= Pi-Po
Myogenic Hypothesis
1.0
DIAMETER
NORMALIZED
0.9
0.8
0.7
0.6
0.5
0
50
100
150
TRANSMURAL PRESSURE (mmHg)
Local modulators of blood flow
• Nitric Oxide is a potent vasodilator that
relaxes vascular smooth muscle and is
released when flow is increased to a
vascular bed.
• Endothelin is a family of peptides that are
potent vasoconstrictors.
What causes exercise hyperemia?
• A collection of examples that do not alter exercise hyperemia ?
– Substances released by active muscle
• Nitric oxide, ATP, Prostaglandins, Adenosine
– Mechanical pumping of muscle
– Nerves
• Sympathetic withdrawal, Sympathetic vasodilator fibers,
Acetylcholine from muscle nerve fibers
•
Maybe a combination of factors synergize.
• Maybe there is (are) some unknown factor(s).
• Note: Some of these substances are important during ischemia
(e.g. adenosine) or when oxygen demand and delivery are briefly
mismatched
Steady state exercise causes intermittent ischemia
Figure 84-8 Effects of muscle exercise on blood flow in the calf of a leg during strong rhythmical contraction. The blood flow was much less during contraction than between contractions.
(Redrawn from Barcroft H, Dornhors AC: Blood flow through human calf during rhythmic exercise. J Physiol 109:402, 1949.)
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Extrinsic Control
• Autonomic Nervous system
• Circulating hormones
Typical integrated (mean voltage) record of multiunit muscle sympathetic
nerve activity (MSNA)
Muscle Nerve Vol.36, 5 Pages: 595-614
Muscle Nerve Vol.36, 5 Pages: 595-614
Illustration showing the predominant neural control systems that regulate skeletal muscle blood flow
during exercise
Thomas, G. D. et al. J Appl Physiol 97: 731-738 2004;
doi:10.1152/japplphysiol.00076.2004
Copyright ©2004 American Physiological Society
Muscle arteries are, but capillaries and veins are not, innervated in C57BL6 mice
Mesenteric
vein
Femoral
artery
Scale bar = 100 m .
J. Of Neuroscience Methods 184:124-128,2009
Mesenteric
Artery
Gracilis Feed
artery
Working muscles compete for blood
flow
Med. Sci. Sports Exer. 38:797,2006
Capillaries are not just smooth
tubes
endothelial glycocalyx
Current Opinion in Anaesthesiology. 22(2):155-162, April 2009.
3
Current Opinion in Anaesthesiology. 22(2):155-162, April 2009.
With regard to control of blood
flow all tissues are not created
equal
Cerebral Blood Flow
Sports Medicine. 37(9):765-782, 2007.
Brain Blood Flow is very
sensitive to PaCO2
X
X
Mohrman and Heller et al
Arterial PCO2 is a cerebral vasodilator
Contrary to popular belief cerebral
blood flow increases during exercise
• The magnitude of the increase is dependent
on the method used to assess blood flow
– Xenon gas washout
– Doppler flow
• The flow response is dependent on exercise
intensity
Exercise & Sport Sciences Reviews. 37(3):123-129, July 2009.
Skeletal Muscle
Figure 84-8 Effects of muscle exercise on blood flow in the calf of a leg during strong rhythmical contraction. The blood flow was much less during contraction than between contractions.
(Redrawn from Barcroft H, Dornhors AC: Blood flow through human calf during rhythmic exercise. J Physiol 109:402, 1949.)
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© 2005 Elsevier
Exercise Physiology, McArdle, Katch and Katch, Lippincott Williams and Wilkins 7th edition
CV=Collecting venule
AA=Arcade artery
TA=Transverse
arteriole
AV=Arcade Venule
Figure 24-5 Microvascular units in skeletal muscle. A, A feed artery (FA) branches into primary arterioles, which after two more orders of branching gives rise to transverse arterioles (3A),
which in turn gives rise to terminal arterioles (4A). B, The terminal arteriole supplies a microvascular unit (1 mm in length).
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© 2005 Elsevier
August Krogh (Univ. of Copenhagen)
was awarded the Nobel Prize for
Medicine on October 28, 1920 for
discovering how increased O2 uptake
by tissue is regulated via the
recruitment of capillaries
Basic premise: Diffusion depends on the concentration gradient
and diffusion distance.
To increase the rate of O2 diffusion (e.g. exercise) you either
increase the concentration gradient or decrease diffusion
distance
200510:44
Elsevier
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PM)
rat spinotrapezius muscle
44% type I
6% type IIA
18% type IID/X
32% type II B
Microcirculation
(rat spinotrapezius)
Terminal
Arteriole
2 capillaries
Collecting
Venule
Microcirculation Exercise
(rat spinotrapezius)
Microcirculation Vasodilator
(rat spinotrapezius)
Sodium Nitroprusside=releases nitric oxide
Krogh’s model is incomplete?
• Capillaries are not straight and they are
stretched when sarcomere length is increased
• Capillaries are not recruited they are always
open
• Capillary hematocrit increases during exercise
(10-15% to 30-40%)
• PO2 is very low in mitochondria at rest
• Oxygen can diffuse from arterioles
• Flow can be countercurrent
• Mouse Soleus Muscle
Erythrocyte
Mitochondria
0.5 m
Dynamics of Muscle Microcirculatory Oxygen Exchange. POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports &
Exercise. 37(9):1559-1566, September 2005.
Tissue oxygen is very low
Dynamics of Muscle Microcirculatory Oxygen Exchange. POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports &
Exercise. 37(9):1559-1566, September 2005.
Flow increases very rapidly with the first contraction
POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
Diffusion is determined by capillary PO2 and diffusive capacity
POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
Spinotrapesius muscle and microvascular PO2
POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
Low flow states limit dynamic vascular response to exercise
CHF=congestive heart failure
POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
Counter current flow
Microvas. Res 55:249-259,1998.
Proposed schematic blood flow patterns in muscle in vivo under basal conditions and
following a physiological rise in plasma insulin
Clark, M. G. Am J Physiol Endocrinol Metab 295: E732-E750 2008;
As O2delivery decreases, the speed with which the tissue can respond to O2 demand
slows (↑τ)
Delivery
dependent
VO2 kinetics
Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008.
Muscle
metabolism
dependent
VO2 kinetics
All muscles are not the same
Figure 60-2 A to C, Properties of fiber types (i.e., motor units in gastrocnemius muscle). The top row shows the tension developed during single twitches for each of the muscle types; the
arrows indicate the time of the electrical stimulus. The middle row shows the tension developed during an unfused tetanus at the indicated stimulus frequency (pps, pulses per second). The
bottom row shows the degree to which each of the fiber types can sustain force during continuous stimulation. The time scales become progressively larger from the top to bottom rows,
with a break in the bottom row. In addition, the tension scales become progressively larger from left (fewer fibers per motor unit) to right (more fibers per motor unit). (Data from Burke
RE, Levine DN, Tsairis P, et al. J Physiol 1977; 234:723-748.)
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Muscles are not the same
• Slow-twitch oxidative
• Fast-twitch glycolytic
• Fast-twitch oxidative
• e.g. slow-twitch vs. white fast twitch fibers
have increased capillarization, arteriolar
density, oxidative capacity, and
endothelium-dependent dilation
Microvascular PO2 following 1Hz stimulation
Soleus
White Gastroc.
Mixed Gastroc.
Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008.
They are recruited differently in response
to gradual increases in exercise intensity
• First recruit slow oxidative then fast
glycolytic
Figure 60-6 Dependence of VO2 on mechanical power output. Training increases VO2max.
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© 2005 Elsevier
Training
• Structural remodeling of the vascular tree
• Altered vasomotor activity of arteries and
arterioles
Acta Physiologica Vol. 193, 2 Pages: 139-150,2008
ET= endurance trained
10–12 weeks of treadmill running
30 m/min
60 min/day,
5 days/week
IST=interval sprint-training
six 2.5-min exercise bouts
4.5-min rest between bouts
(60 m/min, 15% incline)
5 days/week
Gr=red gastroc
s=soleus
Gw=white gastroc Gm=mixed gastroc
J Physiol Pharmacol. 2008 December; 59(Suppl 7): 71–88.
Coronary blood flow
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Figure 24-4 Coronary blood flow cycle. Bands at beginning of systole and diastole reflect isovolumetric contraction and relaxation, respectively.
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© 2005 Elsevier
Figure 21-5 Diagram of the epicardial, intramuscular, and subendocardial coronary vasculature.
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© 2005 Elsevier
Hemodynamic responses to treadmill exercise in dogs
Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008;
Overview of the effect of exercise on myocardial oxygen balance
Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008;
Schematic drawing of a coronary arteriole and the various influences that determine
coronary vasomotor tone and diameter
Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008;
Nitric oxide (NO) release throughout the exercise training cycle. The improvement in NO-related vasodilation is observed in short- to
medium-term exercise training, whereas prolonged exercise is associated with arterial remodelling through an increase in vessel diameter.
Furthermore, strenuous exercise may promote endothelium release of reactive oxygen species (ROS) as an additive source of oxidative
stressors (modified from Green et al.[32]). cGMP = cyclic guanosine monophosphate; eNOS = endothelial nitric oxide synthase; GC =
guanylate cyclase; GTP = guanosine triphosphate.
Sports Medicine. 39(10):797-812, October 1, 2009.
The end