1. Zeljko Dujic, MD, PhD Department of Integrative Physiology, University of Split School of Medicine, Croatia

2. Presentation outline Breath hold diving a)Historical overview b)Challenging the traditional concepts c)Physiological diving response d)Hemodynamic impacts e)Similarities to OSA

3. Historical overview of breath-hold diving  Reaches long ago in the past (fishing, collection of sponges and pearls)  Ama divers – 2 000 years ago  After World War II became an international sport

4. Apnea disciplines and current records  Static apnea World record: 11 min 35 sec  Dynamic apnea World record: 265 m  Constant weight World record: 123 m  No limit World record: 214 m

6. Diving depth: Boyle’s law (the volume to which compressed gas is reduced due to increase in surrounding pressure) Boyle’s law (the volume to which compressed gas is reduced due to increase in surrounding pressure) The influence of the hydrostatic pressure on the chest wall, heart and arteries Professional breath hold diver, - TLC on the surface 9.6 l, RV 2.2 l - on the depth of 133 msw according Boyle’s law TLC should be reduced to 0.67 l? - collapse of the lungs?

7.  Redistribution of the blood from the periphery to the intrathoracic vascular pool and heart (more than 1 liter) under the influence of the increased hydrostatic pressure  For the enlargement of maximal diving depth, diver begins with the largest volume of the air in the lungs (squeezing out the blood from intra-thoracic vascular pool before dive)  Ama exhalation through the whistle  Air packaging in lungs (squeezes out the blood and increases VC from 22-39 %) Danger: rupture of the alveoli and loss of the consciousness

8. Apnea time

9. Apnea time depends on following parameters: 1.Physiologic response to hypercapnia and hypoxia 2. Intensity of metabolism (assisted dives-pendulums, cold water increases 3 fold O2 consumption) 3. Capacities for O2 and CO2 (TLC, training - larger activity of the anaerobic and reduced aerobic metabolism, hyperventilation) 4. Psychological tolerability to hypercapnia and hypoxia

10. Physiological challenges during apnea diving  Physiological/psychological response to hypoxia and hypercapnia  PaO 2 – 30 mmHg, SaO 2 – 50%, PaCO 2 – 55 mmHg  Extreme ambient hydrostatic pressure  Barotrauma at descent and ascent  Pulmonary edema and alveolar hemorrhage  Increased gas uptake and nitrogen supersaturation  N 2 narcosis  Decompression sickness (Deco stops) From Lindholm & Lundgren, J Appl Physiol. 2009 Jan;106(1):284-92.

11. Diving response Paul Bert (1870) reported reduced heart rate (bradycardia) in forcefully diving ducks Numerous animal (birds and mammals) and human research

12. Human Diving response 1. Changes of cardiac rhythm (bradycardia) 2. Peripheral vasoconstriction and redistribution of blood to the central blood reservoir 3. Arterial pressure increase 4. Reduction of cardiac output 5. Contraction of the spleen? (observation from our laboratory)

13. 1. Changes in cardiac rhythm  Initial anticipatory tachycardia (stimulation of the lung mechanoreceptors; hyperventilation; excitement?)  Increased parasympathetic input to SA node (Irving 1963.)  immersion of the face in the cold water  enlargement of venous inflow and distention of heart cavities  Arrhythmias (bradyarrhythmia and extra beats)

14. Slika 5.8

15. 2. Peripheral vasoconstriction and blood redistribution  Increased sympathetic outflow to the periphery – reduced blood flow to the peripheral tissues and skin  A naerobic metabolism on the periphery (lactate increase)  Blood centralization to the brain and heart  100 % increase of cerebral flow through middle cerebral artery (MCA)

17.  significant increase of blood flow through the carotid artery  100 % ↑ of the cerebral flow through middle cerebral artery (MCA) with ultrasound (TCD)  CO 2 retention - cerebral vasodilatation - prevention of hypoxic damages  cerebral desaturation

18. OSA

19. Near InfraRed Spectroscopy  noninvasive  continuous  measurement of oxygen availability at the level of microcirculation  laser diodes set at four different wavelengths (776, 826, 845, 905 nm)  absorption of NIR light by the oxygenated and deoxygenated forms of hemoglobin  emission and detection probe

22. From Palada et al., Respir Physiol Neurobiol. 2007 Aug 1;157(2-3):374-81 MCAV = mid cerebral artery flow BHD = breath-hold divers ND – controls (non divers) Increase of cerebral flow through middle cerebral artery (MCA)

23. 3. Increase in arterial pressure  Significant pressure rise - invasively measured to 290/150 mmHg; a few systolic values to 345 mmHg  Our recent data do not support this findings  Caused by peripheral vasoconstriction

24. 4. Alterations in cardiac output  Increased/ reduced  Surface dry vs. diving apneas

25.  contribution of contractions of diaphragm to the enlargement of the venous inflow throughout struggle phase of the apneas?

26. Two phases of apnea

27. Points of interest  Cardiovascular effects of breath-hold diving  Cerebrovascular impacts of apnea

28. Methodology used  FingerAP, MAP, SV, CO, - Finometer (Modelflow technique); invasive BP  Brain/tissue hemoglobin oxygenation; oxygenation index - NIRS  MCAV – TCD  Microneurography - muscle sympathetic neural activity (MSNA)  Respiratory mechanics – esophageal and gastric balloons From Macefield et al. Auton. Neurosci. 2002.

29. Cerebral and peripheral hemodynamics and oxygenation during maximal dry breath-holds  Despite large increases in cerebral perfusion, regional cerebral desaturation may become a factor limiting the maximal breath- hold duration From Palada et al., Respir Physiol Neurobiol. 2007 Aug 1;157(2-3):374-81

30. Cardiovascular regulation during apnea in elite divers From Heusser et al., Hypertension. 2009 Apr;53(4):719-24

31. Restoration of hemodynamics in apnea struggle phase in association with involuntary breathing movements  Contribution of diaphragm contractions to the enlargement of the venous inflow throughout struggle phase of the apnea From Palada et al., Respir Physiol Neurobiol. 2008 Apr 30;161(2):174-81.

32. Importance of “diving response”  in the saving and redistribution of oxygen reserve throughout apneas  increase in blood flow through vital organs (brain and heart)  decrease of blood flow trough the periphery (splanchnic, muscular and skin vascular pool)

33. Diving response will appear in:  breath hold diving in the depth  the surface apnea with face immersion in the cold water  the surface apnea without face immersion (with or without cold stimulus to the face)

34. Influence of the face immersion on diving response

35. Involuntary breathing movements improve cerebral oxygenation during apnea struggle phase From Dujic et al., J Appl Physiol. 2009 Dec;107(6):1840-6.

36. Involuntary breathing movements improve cerebral oxygenation during apnea struggle phase From Dujic et al., J Appl Physiol. 2009 Dec;107(6):1840-6.

37. Fainting during breath-hold From Dzamonja et al Clin Auton Res 2010, 20(6):381-4. Sympathetic withdrawal

38. Conclusion Increased sympathetic activity, restoration of hemodynamic parameters through the IBM and CO2-mediated central vasodilatation act synergistically to improve cerebral oxygenation and enable prolongation of maximal apnea time.

39. The role of spleen in diving response  Significant reservoir of blood to many land and water mammals (RBC, WBC, platelets)  Exercise and diving cause the contraction of the spleen  Increased adrenergic activity (α1-stimulation)  Constitutive part of SNS? From Bakovic et al., J Appl Physiol. 2003;95(4):1460-6.

40. Spleen volume and blood flow response to repeated breath-hold apneas From Bakovic et al., J Appl Physiol. 2003;95(4):1460-6.

41. Breath-hold diving and Obstructive sleep apnea  Includes three most important symptoms of sleep apnea syndrome: cyclic hypoxemia, hypercapnia and absence of ventilation  Extrapolation of the results to the OSA and connection between OSA and hypertension  Unique human model of OSA?

42. Breath-hold divers as models for studying OSA  Cerebrovascular reactivity and sympathetic central chemoreflex sensitivity are unchanged in elite breath- hold divers during hypercapnia From Dujic et al., J Appl Physiol. 2008;104(1):205-11.

43. Breath-hold divers as models for studying OSA From Narkiewicz er al., Circulation. 1999 Mar 9;99(9):1183-9. From Breskovic et al., Auton Neurosci. 2010;154(1-2):42-7. Isocapnic hypoxia

44. Conclusions  Contrary to obstructive sleep apnea patients, breath hold divers are not exposed to excessive sympathetic activation.  Autonomic, ventilatory, and cardiovascular responses to hypoxia and hypercapnia are normal in elite divers  Repeated voluntary exposure to intermittent hypoxia/hypercapnia in the absence of additional risk factors do not have a negative chronic impact on central and peripheral chemosensitivity Apnea divers OSA voluntary; end-inspiratoryinvoluntary; end-expiratory 3-4 times weekly; 1-1.5hevery time while sleeping usually younger ageusually older age usually healthyusually have comorbidities

45. Ongoing studies  Further characterization of IBMs – respiratory mechanics – transdiaphragmatic pressure  IBMs – brain survival response/reflex  Analyses of discharge properties of sympathetic neural system  Unique coactivation of SNS and PNS  Spleen – the importance of large platelets recruitment in acute coronary incidents  Heart failure – autonomic adaptations, mitochondrial function, intervention

46. Thank you www.mefst.hr/physiology