TY - JOUR T1 - Ischemic Preconditioning and Left Ventricular Dysfunction: A Novel Mechanism & Model for Pulseless Electrical Activity JF - bioRxiv DO - 10.1101/468710 SP - 468710 AU - Kaustubha D Patil AU - Richard S Tunin AU - Sarah J Fink AU - Susumu Tao AU - Henry R Halperin Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/11/12/468710.abstract N2 - Background Pulseless electrical activity (PEA) is a very common rhythm in cardiac arrest and survival is ≈ 5%. Population data suggest coronary ischemia significantly contributes to PEA, but the mechanism is unknown.Objectives We hypothesize ischemic preconditioning (IPC) in the setting of left ventricular (LV) dysfunction can convert ischemia-induced ventricular fibrillation (VF) into ischemia-induced PEA.Methods Using percutaneous coronary interventions in anesthetized swine, we studied the effect of IPC prior to ischemia on arrhythmic burden in normal animals and in animals with LV dysfunction. IPC protocol: four cycles of three minutes of coronary occlusion followed by seven minutes of reperfusion. Chronic LV dysfunction protocol: two serial infarcts in two coronary territories, separated by one week of recovery.Results In normal animals, IPC prior to ischemia significantly reduced VF incidence (2/8 IPC vs. 7/8 control). In IPC animals with VF, the time to VF was significantly delayed (37.2 ± 7.3 min vs. 20.7 ± 4.9 min, p<0.005). In chronic LV dysfunction animals (EF 15% ± 5%), ischemia caused PEA in all animals (18/18). In non-preconditioned animals, VF followed PEA in all cases (12/12). In preconditioned animals, PEA sustained without VF in 2/6 animals. In 4/6 animals, PEA was prolonged and time to VF was significantly delayed compared to non-preconditioned animals (33.7 ± 7.8 min vs. 12.2 ± 5.0 min, p<0.0001).Conclusion IPC delays/prevents VF. IPC with LV dysfunction prior to ischemia produces prolonged PEA. IPC with LV dysfunction prior to ischemia is likely an important mechanism for human PEA arrest. This is the first animal model of ischemic pulseless electrical activity.AbbreviationsVTventricular tachycardiaVFventricular fibrillationPEApulseless electrical activityIPCischemic preconditioningLVleft ventricleLADleft anterior descendingRCAright coronary arteryLCXleft circumflexACLSadvanced cardiac life supportRHreactive hyperemiaECGelectrocardiogramMAPmean arterial pressure ER -