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