title: Understanding pacing postconditioning-mediated cardiac protection: a role of oxidative stress and a synergistic effect of adenosine.
abstract: We and others have demonstrated a protective role for pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury in the heart; however, the underlying mechanisms behind these protective effects are not completely understood. In this study, we wanted to further characterize PPC-mediated cardiac protection, specifically identify optimal pacing sites; examine the role of oxidative stress; and test the existence of a potential synergistic effect between PPC and adenosine. Isolated rat hearts were subjected to coronary occlusion followed by reperfusion. PPC involved three, 30 s, episodes of alternating left ventricular (LV) and right atrial (RA) pacing. Multiple pacing protocols with different pacing electrode locations were used. To test the involvement of oxidative stress, target-specific agonists or antagonists were infused at the beginning of reperfusion. Hemodynamic data were digitally recorded, and cardiac enzymes, oxidant, and antioxidant status were chemically measured. Pacing at the LV or RV but not at the heart apex or base significantly (P < 0.001) protected against ischemia-reperfusion injury. PPC-mediated protection was completely abrogated in the presence of reactive oxygen species (ROS) scavenger, ebselen; peroxynitrite (ONOO-) scavenger, uric acid; and nitric oxide synthase inhibitor, L-NAME. Nitric oxide (NO) donor, snap, however significantly (P < 0.05) protected the heart against I/R injury in the absence of PPC. The protective effects of PPC were significantly improved by adenosine. PPC-stimulated protection can be achieved by alternating LV and RA pacing applied at the beginning of reperfusion. NO, ROS, and the product of their interaction ONOO-play a significant role in PPC-induced cardiac protection. Finally, the protective effects of PPC can be synergized with adenosine.
authors.affiliation: Department of Physiology, Faculty of Medicine, Health Sciences Center, Kuwait University, Jabriya, Kuwait. Fawzi.b@hsc.edu.kw.
authors.forename: Fawzi A
authors.initials: FA
authors.lastname: Babiker
authors.affiliation: Biochemistry, Faculty of Medicine, Health Sciences Center, Kuwait University, Jabriya, Kuwait.
authors.forename: Aishah
authors.initials: A
authors.lastname: Al-Jarallah
authors.affiliation: Department of Physiology, Faculty of Medicine, Health Sciences Center, Kuwait University, Jabriya, Kuwait.
authors.forename: Shaji
authors.initials: S
authors.lastname: Joseph
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000009:adverse effects; D003326:Coronary Circulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000009:adverse effects / Q000627:therapeutic use; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D057775:Ischemic Postconditioning / Q000009:adverse effects / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D020030:Nitric Oxide Donors / Q000009:adverse effects / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019001:Nitric Oxide Synthase; D000241:Adenosine
keywords: Ischemia reperfusion; No; Pacing postconditioning; ROS