1. An introduction to Intrathoracic Pressure Regulation Therapy 49-2057-000, 01

3. What is Intrathoracic Pressure Regulation? Intrathoracic Pressure Regulation (IPR) is a therapy that enhances negative pressure in the chest and has been shown in studies to effectively improve circulation of blood to the brain and other vital organs. 1

4. Pressure and Natural Physiology

5. Intrathoracic Pressure The body continually regulates the circulation of blood by using positive and negative pressures inside the thoracic cavity to maintain equilibrium.

6. Positive vs. Negative Pressure  PUSHES air away  Inhibits blood return  Principle behind CPAP therapy The thoracic cavity is like a bellows…  Creates a vacuum  PULLS fluid and air in  Principle behind IPR therapy Negative Pressure Positive Pressure

7. Normal Physiology Conversely when you inhale (inspiration), you create a slight negative pressure, which…  Pulls air into lungs  Returns blood to the chest  Lowers ICP When you exhale (exhalation), you create a slight positive pressure, which…  Forces air out  Inhibits blood return to the heart  Increases intracranial pressure (ICP)

8. Moreno et al. Respiratory regulation of splanchnic and systemic venous return. Am J Physiol 1967;213:455-465. Effect of Intrathoracic Pressure on Blood Flow Intrathoracic Pressure (cmH 2 O) Blood Flow, Abdominal Vena Cava (l/min -1 ) Respiration and circulation are closely linked. Dating back to 1967, we have known there is an inverse relationship between intrathoracic pressure and blood flow. As intrathoracic pressure decreases... blood flow increases.

9. 2 Seconds per Division 5 -10 0 mmHg 55 mmHg 75 35 -5 cmH 2 O 5 -15 55 mmHg 75 35 Aortic Pressure Intracranial Pressure Intrathoracic Pressure Cerebral Perfusion Pressure Pressures with No Intervention Intrathoracic Pressure and ICP Linked Convertino et al. Resp Care 2011;56:846-857. Animal Model with 40% Bleed - No Intervention

10. Compensation and Decline

11. Normal Physiology - Compensation The body regulates pressures as part of its normal compensatory response. Under stress, such as when exercising, one breathes harder, faster, deeper; this… Enhances negative pressure in the thoracic cavity Lowers intracranial pressure (ICP) to improve blood flow to the brain

12. However, sometimes a body is unable to adequately compensate. Example: Shock 1.Heart rate increases in an effort to maintain sufficient blood flow 2.Intrathoracic pressure is modulated in an effort to increase perfusion 3.Eventually, body is unable to adequately compensate and blood pressure drops Result: Insufficient perfusion to protect the brain and other vital organs. Body in Trouble

13. Intrathoracic Pressure Regulation (IPR)

14. Positive Pressure Results: 1.Drives fluid out of the lungs 2.Decreases preload 3.Decreases cardiac output 4.Decreases blood pressure Continuous positive airway pressure (CPAP) and positive pressure ventilation (PPV) are common and well accepted therapies for pulmonary edema.

15. IPR = Negative Pressure IPR leverages negative intrathoracic pressure to enhance perfusion; studies 1 have shown that it... Enhances negative intrathoracic pressure 2 (i.e. increases the vacuum in the chest), which... ① Draws more blood back to the heart 3,7 (i.e. increases preload), which leads to increased cardiac output and blood pressure and ① Decreases intracranial pressure (ICP) 4,5,6 which makes it easier to get blood into and out of the brain (i.e. increases cerebral perfusion)

16. Intrathoracic Pressure Regulation (IPR) Normal Breathing IPR Therapy Enhances Negative Pressure (Increased cardiac output) (Decreased cardiac output)

18. IPR Therapy is simply using the “other side of pressure,” enhancing negative pressure to improve perfusion. Studies 1 show that IPR Therapy:  Enhances negative intrathoracic pressure 2  Increases preload 3  Increases cardiac output 3  Increases blood pressure 7  Lowers ICP 4,5  Results in more forward cerebral blood flow, better perfusion of the brain. 6 Impact of IPR ResQGARD ITDResQPOD ITD

19. Intrathoracic Pressure Regulation Therapy helping the body help itself Intrathoracic Pressure

20. Impedance Threshold Devices (ITDs) Deliver IPR ResQGARD ITD ResQPOD ITD Studies Show 1 How it Works Enhances circulation in patients undergoing CPR during cardiac arrest (profound shock) Prevents the influx of air during chest wall recoil to enhance negative intrathoracic pressure Enhances circulation in spontaneously breathing patients with low blood pressure (shock) Creates a slight amount of therapeutic resistance during inhalation to enhance negative intrathoracic pressure

21. The Evidence

22. 2 Seconds per Division Aortic Pressure Intracranial Pressure Intrathoracic Pressure Cerebral Perfusion Pressure No IPR 5 -10 0 mmHg 55 mmHg 75 35 -5 cm H 2 O 5 -15 55 mmHg 75 35 With IPR Impact of IPR on Pressures Convertino et al. Resp Care 2011;56:846-857. Animal Model with 40% Bleed

23. Time (secs) Mean CBF Velocity (cm/sec) IPR On IPR Off 4003002001000 30 40 50 60 70 80 Cooke et al. Human autonomic and cerebrovascular responses to inspiratory impedance. J Trauma 2006;60:1275-1283. Cerebral Blood Flow ON / OFF Effect of IPR

24. For More Information www.AdvancedCirculatory.com info@AdvancedCirculatory.com 1-877-737-7763

25. References 1.The generally cleared indication for the ResQPOD and ResQGARD ITDs available for sale in the United States is for a temporary increase in blood circulation during emergency care, hospital, clinical, and home use. Research is ongoing in the United States (US) to evaluate the longer-term benefits of the ResQPOD and ResQGARD for other specific indications. The studies listed here are not intended to imply specific outcomes-based claims not yet cleared by the US FDA. 2.Lurie KG, Zielinski T, McNite S, Aufderheid T, Voelckel W. Use of an inspiratory impedance valve improves neurologically intact survival in a porcine model of ventricular fibrillation. Circulation 2002; 105(1):124-129. 3.Lurie, KG, Voelckel WG, Zielinski T, et al. Improving standard cardiolpulmonary resuscitation with an inspiratory impedance threshold valve in a porcine model of cardiac arrest. Anesth Analg 2001;93:649- 55. 4.Aufderheide TP, Alexander C, Lick C, et al. from laboratory science to 6 emergency medical services systems: new understanding of the physiology of cardiopulmonary resuscitation increases survival rates after cardiac arrest. Crit Care Med 2008;36(11):S397-S404. 5.Alexander C, Yannopoulos D, Aufderheide T, et al. Dual mechanism of blood flow augmentation to the brain using an impedance threshold device in a pediatric model of cardiac arrest. Circulation 2007; 116(16):II-433. 6.Lurie KG, Mulligan KA, McNite S, Detloff B, Lindstrom P, Lindner KH. Optimizing standard cardiopulmonary resuscitation with an inspiratory impedance threshold valve. Chest 1998;113(4):1084- 1090. 7.Pirrallo RG, Aufderheide TP, Provo TA, Lurie KG. Effect of an inspiratory impedance threshold device on hemodynamics during conventional manual cardiopulmonary resuscitation. Resuscitation 2005;66:13-20.