Tissue blood flow and exercise Brain Heart Muscle.
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Transcript of Tissue blood flow and exercise Brain Heart Muscle.
Tissue blood flow and exercise
•Brain
•Heart
•Muscle
BL
OO
D F
LO
W
Rate of metabolism
Control of tissue flow
• Intrinsic Control
• Extrinsic control
• Long term control
Tissue
Height~ perfusion pressure
Perfusion pressure (mmHg)
0 20 40 60 80 100 120 140 160 180
Blo
od
flo
w (
ml/m
in/1
00g
)
0
2
4
6
8
10
12
14
Figure 20-14 Autoregulation of blood flow.
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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
cellsSmooth muscle
Adenosine
CapillaryArteriole
Precapillary sphincter
Smooth muscle
Adenosine Hypothesis
Flow Oxygen delivery
O2 ATP ADP AMP
Adenosine vasodilation
restore oxygen delivery
Inflo
win
g pr
essu
re (
mm
Hg)
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7
Blo
od F
low
0
20
40
60
80
100
Time (min)
Reactive Hyperemia
Transmural pressure
Pi
Po
Pt= Pi-Po
Myogenic Hypothesis
0 50 100 1500.5
0.6
0.7
0.8
0.9
1.0
NO
RM
AL
IZE
D
TRANSMURAL PRESSURE (mmHg)
DIA
ME
TE
R
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
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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Steady state exercise causes intermittent ischemia
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: 595-614Muscle Nerve Vol.36, 5 Pages: 595-614
Copyright ©2004 American Physiological Society
Thomas, G. D. et al. J Appl Physiol 97: 731-738 2004;doi:10.1152/japplphysiol.00076.2004
Illustration showing the predominant neural control systems that regulate skeletal muscle blood flow during exercise
Scale bar = 100 m . J. Of Neuroscience Methods 184:124-128,2009
Muscle arteries are, but capillaries and veins are not, innervated in C57BL6 mice
Mesenteric vein Mesenteric
Artery
Femoral artery
Gracilis Feed artery
Working muscles compete for blood flow
Med. Sci. Sports Exer. 38:797,2006
Capillaries are not just smooth tubes
3
endothelial glycocalyx
Current Opinion in Anaesthesiology. 22(2):155-162, April 2009.
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
Arterial PCO2 is a cerebral vasodilator
Mohrman and Heller et al
XX
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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Exercise Physiology, McArdle, Katch and Katch, Lippincott Williams and Wilkins 7th edition
AA=Arcade artery
AV=Arcade Venule
TA=Transverse arteriole
CV=Collecting 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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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
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rat spinotrapezius muscle 44% type I
6% type IIA 18% type IID/X
32% type II B
Microcirculation(rat spinotrapezius)
Collecting Venule
Terminal Arteriole
2 capillaries
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
Dynamics of Muscle Microcirculatory Oxygen Exchange. POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
• Mouse Soleus Muscle
Erythrocyte
Mitochondria
0.5 m
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.
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
Spinotrapesius muscle and microvascular PO2
POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.
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
Microvas. Res 55:249-259,1998.
Counter current flow
Clark, M. G. Am J Physiol Endocrinol Metab 295: E732-E750 2008;
Proposed schematic blood flow patterns in muscle in vivo under basal conditions and following a physiological rise in plasma insulin
As O2delivery decreases, the speed with which the tissue can respond to O2 demand slows (↑τ)
Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008.
Delivery dependent VO2 kinetics
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
Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008.
Soleus
White Gastroc.Mixed Gastroc.
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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Training
• Structural remodeling of the vascular tree
• Altered vasomotor activity of arteries and arterioles
Acta Physiologica Vol. 193, 2 Pages: 139-150,2008
J Physiol Pharmacol. 2008 December; 59(Suppl 7): 71–88.
ET= endurance trained10–12 weeks of treadmill running30 m/min60 min/day,5 days/weekIST=interval sprint-training six 2.5-min exercise bouts4.5-min rest between bouts (60 m/min, 15% incline)5 days/week
Gr=red gastroc s=soleusGw=white gastroc Gm=mixed gastroc
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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Figure 21-5 Diagram of the epicardial, intramuscular, and subendocardial coronary vasculature.
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Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008;
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
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