title: Protective effects of NHE1 inhibition with sabiporide in an experimental model of asphyxia-induced cardiac arrest in piglets.
abstract: The present study investigated the protective effects of a novel NHE1 selective inhibitor, sabiporide, in a porcine model of asphyxia-induced cardiac arrest. Asphyxial cardiac arrest was induced by endotracheal tube clamping (ETC). The animals remained untreated for 3 min after loss of aortic pulsations (LOAP), and followed by chest compression and defibrillation. Sixteen of eighteen pigs had return of spontaneous circulation (ROSC), and were randomly assigned to two study groups. Group 1: vehicle control. Group 2: 3mg/kg sabiporide was given at 15 min after ROSC. Post-arrest myocardial dysfunction was present in both groups, and progressed over hours. Animals treated with sabiporide had less wall motion abnormality and higher left ventricular ejection fraction than control animals (33% in control group vs. 47% in sabiporide group). Sabopiride treatment also significantly improved post-arrest arterial blood pressure by 25% and cardiac stroke volume by 44%, and improved mixed-venous blood oxygen saturation by 38% and oxygen delivery by 118%. Furthermore, compared to the control group, the sabiporide group also had higher blood flows in the brain, heart, kidney, liver and spleen at 30 min after ROSC. There was no significant blood flow difference in distal ileum mucosa between control and sabiporide groups. In addition, sabiporide treatment significantly reduced cardiac myeloperoxidase (MPO) activity by 53% and cardiac troponin I by 51%, and reduced the plasma level of TNF-α by 52% and IL-6 by 41%. This study shows that post-arrest pharmacological conditioning with sabiporide affords protection from whole body ischemia-reperfusion injury in this model of asphyxia-induced cardiac arrest and resuscitation.
authors.affiliation: Department of Research, Mount Sinai Medical Center, Miami Beach, FL, USA.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Lin
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D015850:Interleukin-6 / Q000097:blood; D023421:Models, Animal; D017682:Myocardial Stunning / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D019210:Troponin I / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D002316:Cardiotonic Agents; D027682:Cation Transport Proteins; D006146:Guanidines; D015850:Interleukin-6; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D010100:Oxygen; C476560:sabiporide