sabiporide and Asphyxia

The present study tested the hypothesis that addition of an inhibitor of Na(+)/H(+) exchanger (NHE1) to sodium bicarbonate might improve the response to base therapy from prolonged asphyxial cardiac arrest in piglets.. Asphyxial cardiac arrest was induced by endotracheal tube clamping. Animals were randomly assigned to four study groups: (i) vehicle control, (ii) administration of sabiporide (NHE1 inhibitor), (iii) administration of sodium bicarbonate, and (iv) administration of sabiporide and sodium bicarbonate.. Administration of sodium bicarbonate alone did not affect survival, hemodynamic measures, and regional blood flow to critical tissues such as brain, heart, kidney, liver, and spleen. In contrast, sabiporide given alone or combined with sodium bicarbonate improved these. Furthermore, treatment with sabiporide reduced accumulation of neutrophils, reduced cytokine production in the lung, and reduced plasma levels of cardiac troponin-I, alanine aminotransferase, aspartate aminotransferase, and urea. In addition, the combined use of sabiporide and sodium bicarbonate had more profound reduction in interleukin (IL)-6 and IL-10, compared to sabiporide alone.. These results suggest that addition of sabiporide to the administration of sodium bicarbonate might improve hemodynamic response and dampen the inflammatory cascade noted with cardiac arrest, and therefore being an attractive option in the treatment of cardiac arrest.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Asphyxia; Cytokines; Echocardiography; Guanidines; Heart Arrest; Hemodynamics; Neutrophils; Regional Blood Flow; Sodium Bicarbonate; Sodium-Hydrogen Exchangers; Swine; Troponin I; Urea

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.

Topics: Animals; Asphyxia; Blood Circulation; Blood Pressure; Cardiotonic Agents; Cation Transport Proteins; Guanidines; Heart Arrest, Induced; Interleukin-6; Models, Animal; Myocardial Stunning; Myocardium; Oxygen; Oxygen Consumption; Peroxidase; Reperfusion Injury; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers; Stroke Volume; Swine; Troponin I; Tumor Necrosis Factor-alpha