CPR flow to prime the ischemic heart during cardiac arrest?

Cardiac arrest is unique among cardiac ischemic syndromes in that all circulation must be generated external to the heart. Although, chest compressions deliver limited blood flow, it may be possible to take advantage of this cardiopulmonary resuscitation (CPR) low-flow state to “prime” the heart in advance of return of restoration of spontaneous circulation. Prior investigation has demonstrated improved cardiac function after perfusing the globally ischemic heart with a cardioprotective agent under low-flow perfusion conditions (modeling CPR flow). These results raise the question as to whether CPR-generated flow can be utilized to induce pharmacological post-conditioning in the arrested heart.

low-flow, CPR, post-conditioning, cardioprotect

1. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 2003 Aug;285(2):H579-88.

2. Penna C, Mancardi D, Raimondo S, Geuna S, Pagliaro P. The paradigm of postconditioning to protect the heart. J Cell Mol Med 2008 Apr;12(2):435-58.

3. Penna C, Rastaldo R, Mancardi D, Raimondo S, Cappello S, Gattullo D, et al. Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation. Basic Res Cardiol 2006 Mar;101(2):180-9.

4. Andreadou I, Iliodromitis EK, Farmakis D, Kremastinos DT. To prevent, protect and save the ischemic heart: antioxidants revisited. Expert Opin Ther Targets 2009 Aug;13(8):945-56.

5. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis 2009 Jun;204(2):334-41.

6. Nemlin C, Benhabbouche S, Bopassa JC, Sebbag L, Ovize M, Ferrera R. Optimal pressure for low pressure controlled reperfusion to efficiently protect ischemic heart: an experimental study in rats. Transplant Proc 2009 Mar;41(2):703-4.

7. Bopassa JC, Michel P, Gateau-Roesch O, Ovize M, Ferrera R. Low-pressure reperfusion alters mitochondrial permeability transition. Am J Physiol Heart Circ Physiol 2005 Jun;288(6):H2750-5.

8. Nichol G, Thomas E, Callaway CW, Hedges J, Powell JL, Aufderheide TP, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA 2008 Sep 24;300(12):1423-31.

9. Brown CG, Werman HA, Davis EA, Hobson J, Hamlin RL. The effects of graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine. Circulation 1987 Feb;75(2):491-7.

10. Bradley SM, Gabriel EE, Aufderheide TP, Barnes R, Christenson J, Davis DP, et al. Survival Increases with CPR by Emergency Medical Services before defibrillation of out-of-hospital ventricular fibrillation or ventricular tachycardia: Observations from the Resuscitation Outcomes Consortium. Resuscitation 2010 Feb;81(2):155-62.

11. Wik L, Hansen TB, Fylling F, Steen T, Vaagenes P, Auestad BH, et al. Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation: a randomized trial. JAMA 2003 Mar;19;289(11):1389-95.

12. Jacobs IG, Finn JC, Oxer HF, Jelinek GA. CPR before defibrillation in out-of-hospital cardiac arrest: a randomized trial. Emerg Med Australas 2005 Feb;17(1):39-45.

13. Iwami T, Nichol G, Hiraide A, Hayashi Y, Nishiuchi T, Kajino K, et al. Continuous improvements in “chain of survival” increased survival after out-of-hospital cardiac arrests: a large-scale population-based study. Circulation 2009 Feb

10;119(5):728-34.

14. Zhou Y, Chen D, Ma X, Yang G. Postconditioning in cardiopulmonary resuscitation: a better protocol for cardiopulmonary resuscitation. Med Hypotheses 2009 Sep;73(3):321-3.

15. Yeh ST, Lee HL, Aune SE, Chen CL, Chen YR, Angelos MG. Preservation of mitochondrial function with cardiopulmonary resuscitation in prolonged cardiac arrest in rats. J Mol Cell Cardiol 2009 Dec;47(6):789-97.

16. Aune SE, Yeh ST, Kuppusamy P, Kuppusamy ML, Khan M, Angelos MG. Sivelestat attenuates myocardial reperfusion injury during brief low flow postischemic infusion. Oxid Med Cell Longev 2013;2013:279847. doi: 10.1155/2013/279847. Epub; 2013 May 22.:279847.

17. Abe T, Usui A, Oshima H, Akita T, Ueda Y. A pilot randomized study of the neutrophil elastase inhibitor, Sivelestat, in patients undergoing cardiac surgery. Interact Cardiovasc Thorac Surg 2009 Aug;9(2):236-40.

18. Kambe M, Bessho R, Fujii M, Ochi M, Shimizu K. Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia. Interact Cardiovasc Thorac Surg 2009 Jun;8(6):629-34.

19. Maeda Y, Mitsumizo S, Guo F, Kishi H, Matsuo S, Kobayashi S, et al. Sivelestat relaxes porcine coronary artery via inhibition of Ca2+ sensitization induced by a receptor agonist. J Cardiovasc Pharmacol 2008 May;51(5):476-82.

20. Khan M, Meduru S, Mostafa M, Khan S, Hideg K, Kuppusamy P. Trimetazidine, administered at the onset of reperfusion, ameliorates myocardial dysfunction and injury by activation of p38 MAPK and Akt signaling. J Pharmacol Exp Ther 2010 May;333(2):421-29.