1. Tissue blood flow and exercise Brain Heart Muscle

4. Control of tissue flow Intrinsic Control Extrinsic control Long term control

5. Tissue Height~ perfusion pressure

7. Figure 20-14 Autoregulation of blood flow. Downloaded from: StudentConsult (on 25 February 2010 10:44 PM) © 2005 Elsevier

8. Local Control of Blood Flow Metabolic hypothesis: Blood flow is governed by the metabolic activity of the tissue. Any intervention that reduces O 2 supply gives rise to the formation of vasodilator metabolites. Myogenic hypothesis: The vascular smooth muscle contracts in response to stretch

9. Metabolic hypothesis The metabolic hypothesis suggests that the tissue releases a vasodilator; The potential mediators of this vasodilation are: Adenosine Prostaglandins Lactate

10. Metabolic Hypothesis cells Smooth muscle Adenosine Capillary Arteriole Precapillary sphincter Smooth muscle

11. Adenosine Hypothesis  Flow   Oxygen delivery   O 2  ATP  ADP   AMP   Adenosine  vasodilation  restore oxygen delivery

12. Reactive Hyperemia

13. Transmural pressure PiPi PoPo P t = P i -P o

14. Myogenic Hypothesis

15. 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.

16. 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

17. 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.) Downloaded from: StudentConsult (on 25 February 2010 10:27 PM) © 2005 Elsevier Steady state exercise causes intermittent ischemia

18. Extrinsic Control Autonomic Nervous system Circulating hormones

19. Typical integrated (mean voltage) record of multiunit muscle sympathetic nerve activity (MSNA) Muscle Nerve Vol.36, 5 Pages: 595-614

20. 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

21. 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

22. Working muscles compete for blood flow Med. Sci. Sports Exer. 38:797,2006

23. Capillaries are not just smooth tubes

24. 3 endothelial glycocalyx Current Opinion in Anaesthesiology. 22(2):155-162, April 2009.

26. With regard to control of blood flow all tissues are not created equal

27. Cerebral Blood Flow

28. Sports Medicine. 37(9):765-782, 2007.

29. Brain Blood Flow is very sensitive to PaCO 2 Arterial PCO 2 is a cerebral vasodilator Mohrman and Heller et al X X

30. 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

31. Exercise & Sport Sciences Reviews. 37(3):123-129, July 2009.

32. Skeletal Muscle

33. 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.) Downloaded from: StudentConsult (on 25 February 2010 10:27 PM) © 2005 Elsevier

34. Exercise Physiology, McArdle, Katch and Katch, Lippincott Williams and Wilkins 7th edition

35. AA=Arcade artery AV=Arcade Venule TA=Transverse arteriole CV=Collecting venule

36. 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). Downloaded from: StudentConsult (on 25 February 2010 10:27 PM) © 2005 Elsevier

37. August Krogh (Univ. of Copenhagen) was awarded the Nobel Prize for Medicine on October 28, 1920 for discovering how increased O 2 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 O 2 diffusion (e.g. exercise) you either increase the concentration gradient or decrease diffusion distance

38. Downloaded from: StudentConsult (on 25 February 2010 10:44 PM) © 2005 Elsevier

39. rat spinotrapezius muscle 44% type I 6% type IIA 18% type IID/X 32% type II B

40. Microcirculation (rat spinotrapezius) Collecting Venule Terminal Arteriole 2 capillaries

41. Microcirculation Exercise (rat spinotrapezius)

42. Microcirculation Vasodilator (rat spinotrapezius) Sodium Nitroprusside=releases nitric oxide

43. 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%) PO 2 is very low in mitochondria at rest Oxygen can diffuse from arterioles Flow can be countercurrent

44. 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

45. 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.

46. 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.

47. Diffusion is determined by capillary PO 2 and diffusive capacity

48. Spinotrapesius muscle and microvascular PO 2 POOLE, DAVID; BEHNKE, BRAD; PADILLA, DANIELLE Medicine & Science in Sports & Exercise. 37(9):1559-1566, September 2005.

49. Low flow states limit dynamic vascular response to exercise CHF=congestive heart failure

50. Microvas. Res 55:249-259,1998. Counter current flow

51. 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

52. As O 2 delivery decreases, the speed with which the tissue can respond to O 2 demand slows ( ↑τ ) Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008. Delivery dependent VO 2 kinetics Muscle metabolism dependent VO 2 kinetics

53. All muscles are not the same

54. 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.) Downloaded from: StudentConsult (on 25 February 2010 10:27 PM) © 2005 Elsevier

55. 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

56. Microvascular PO2 following 1Hz stimulation Medicine & Science in Sports & Exercise. 40(3):462-474, March 2008. Soleus White Gastroc. Mixed Gastroc.

57. They are recruited differently in response to gradual increases in exercise intensity First recruit slow oxidative then fast glycolytic

58. Figure 60-6 Dependence of VO2 on mechanical power output. Training increases VO2max. Downloaded from: StudentConsult (on 25 February 2010 10:27 PM) © 2005 Elsevier

59. Training Structural remodeling of the vascular tree Altered vasomotor activity of arteries and arterioles

60. Acta Physiologica Vol. 193, 2 Pages: 139-150,2008

61. J Physiol Pharmacol. 2008 December; 59(Suppl 7): 71–88. 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

62. Coronary blood flow

63. Downloaded from: StudentConsult (on 25 February 2010 11:01 PM) © 2005 Elsevier

64. Figure 24-4 Coronary blood flow cycle. Bands at beginning of systole and diastole reflect isovolumetric contraction and relaxation, respectively. Downloaded from: StudentConsult (on 25 February 2010 10:44 PM) © 2005 Elsevier

65. Figure 21-5 Diagram of the epicardial, intramuscular, and subendocardial coronary vasculature. Downloaded from: StudentConsult (on 26 February 2010 09:53 PM) © 2005 Elsevier

66. Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008; Hemodynamic responses to treadmill exercise in dogs

67. Duncker, D. J. et al. Physiol. Rev. 88: 1009-1086 2008; Overview of the effect of exercise on myocardial oxygen balance

68. 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

69. 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.

70. The end