Oxygen Transport Systems

1. Oxygen Transport Systems Integration of Ventilation, Cardiac, and Circulatory Functions

2. Cardiovascular Function • transportation of O2 and CO2 • transportation of nutrients/waste products • distribution of hormones • thermoregulation • maintenance of blood pressure

7. Long Refractory Period in Cardiac Muscle Prevents Tetany

8. Cardiac Fibers Develop Graded Tension • Frank-Starling Law of the Heart • graded Ca2+ release from SR • dependent on Ca2+ influx through DHP channels

9. Autorhythmic cells depolarize spontaneously leaky membrane SA and AV node

10. Group III Central command input and output

12. Cardiac output affected by: • preload – end diastolic pressure (amount of myocardial stretch) • affected by venous return • afterload – resistance blood encounters as it leaves ventricles • affected by arterial BP • contractility – strength of cardiac contraction • heart rate

13. Mechanisms affecting HRVO2 = HR SV  (a-v O2) Sinoatrial node is pacemaker for heart • spontaneously depolarizes • leakiness to Na+ • influenced by autonomic NS • training down-regulates ß-adrenergic system causing bradycardia

14. Cardiac Output Regulation Extrinsic control • autonomic nervous system • sympathetic NS (1 control at HR >100 bpm) • parasympathetic NS (1 control at HR <100 bpm) • stimulates ß-adrenergic receptors on myocardium • hormonal • EPI, NE

15. Mechanisms affecting SVVO2 = [HR  SV]  (a-v O2) • amount of Ca2+ influx • APs open Ca2+ channels on t-tubules • also stimulates Ca2+ release from SR • length-tension relationship • [Ca2+]-tension relationship • ß1-adrenergic modulation • activates cAMP  phosphorylates L-type Ca2+, SR Ca2+ channels and pumps, troponin •  Ca2+ influx and Ca2+ release from SR • training  LV EDV

16. Intrinsic control • Frank-Starling Principle •  Ca2+ influx w/ myocardial stretch • stretched fibers work at optimal length-tension curve Dotted lines indicate end-systole and end-diastole

17. Cardiovascular Response to Exercise Laughlin, M.H. Cardiovascular responses to exercise. Adv. Physiol. Educ. 22(1): S244-S259, 1999. [available on-line]

18. Cardiovascular Response to Exercise Fick principle VO2 = Q (CaO2 – CvO2) VO2 = [HR SV] (CaO2 – CvO2) VO2 = [BP TPR] (CaO2 – CvO2)

19. Exercise Effects on Cardiac Output •  HR caused by •  sympathetic innervation •  parasympathetic innervation •  release of catecholamines •  SV, caused by •  sympathetic innervation •  venous return

20. Myocardial Mechanisms Influencing SV During Exercise • SV = EDV – ESV • Factors that influence SV • Heart size (LVV) • LV compliance during diastole • Progressive  in ESV with graded exercise is from  contractility • Attributed to  sympathetic NS, length-tension changes • Influx of Ca2+ through L-type Ca2+ channels stimulates Ca2+ from SR release channels (Ca2+-induced Ca2+-release)

21. Role of Ca2+ in Cardiac Function • influx of Ca2+ through L-type Ca2+ channels stimulates Ca2+ from SR release channels (Ca2+-induced Ca2+-release) • amount of Ca2+ released from SR dependent on sarcomere length • SERCA pumps return Ca2+ to sarcoplasmic reticulum • sympathetic -adrenergic stimulation  contractile force and relaxation time • affects Ca2+ sensitivity through phosphorylation • increases length of diastole to  filling time

22. HR and Q responses to exercise intensity

23. SV during graded running Zhou et al., MSSE, 2001

24. Effect of training and maximal exercise on VO2, Q, and a-v O2 difference

25. Effect of training and maximal exercise on VO2, Q, and a-v O2 difference

26. Effects of Exercise on Blood PressureBP = Q  TPR

28. Arterioles and Capillaries • arterioles  terminal arterioles (TA) capillaries collecting venules (CV)  • arterioles regulate circulation into tissues • under sympathetic and local control • precapillary sphincters fine tune circulation within tissue • under local control • capillary density 1 determinant of O2 diffusion

31. Regulation of Blood Flow and Pressure Blood flow and pressure determined by: A. Vessel resistance (e.g. diameter) to blood flow B. Pressure difference between two ends A cardiac output arterioles B A B

32. Effects of Exercise Intensity on TPR

33. Effects of Incremental Exercise on BP

34. Effects of Isometric Exercise on BP

35. Control of Blood Flow Blood flow to working muscle increases linearly with muscle VO2

36. Blood Distribution During Rest

37. Blood Flow Redistribution During Exercise

38. Effect of exercising muscle mass on blood flow

39. (1-adrenergic receptor blocker) 30 s Onset of exercise

41. Local Control of Microcirculation • metabolic factors that cause local vasodilation • PO2 • PCO2 • H+ • adenosine • endothelial factors that cause local vasodilation • nitric oxide (NO) • released with  shear stress and EPI • redistributed from Hb—greater O2 release from Hb induces NO release as well

42. Adenosine metabolism in myocytes and endothelial cells ATP  ADP  AMP  adenosine Adenosine is released in response to hypoxia, ischemia, or increased metabolic work

43. Single layer of endothelial cells line innermost portion of arterioles that releases nitric oxide (NO) causing vasodilation

45. Hemoglobin • consists of four O2-binding heme (iron containing) molecules • combines reversible w/ O2 (oxy-hemoglobin) • Bohr Effect – O2 binding affected by • PO2 • PCO2 • pH • temperature • 2,3-DPG (diphosphoglycerate)

46. CO2 transport

47. Factors affecting Oxygen Extraction Fick principle VO2 = Q  (CaO2 – CvO2)

48. O2 extraction during graded exercise Sympathetic stimulation causes spleen to constrict releasing RBC into blood, thus increasing O2-carrying capacity

49. Bohr effect on oxyhemoglobin dissociation • PO2, pH and  PCO2, temperature, and 2,3 DPG shift curve to left causing greater O2 release

50. Cardiovascular Adaptations to Training