Abstract 12131: Mechanism of Hypokalemia-dependent Arrhythmias in a New Porcine Model of Advanced Heart Failure: Insights Into the Pathophysiology of Increased Afterload in Chronic Myocardial Infarction
Introduction: Hypertension worsens the prognosis of post-myocardial infarction (MI) patients. To examine the underlying mechanisms, we developed a new porcine model of post-MI heart failure with chronically increased afterload (HF/iAL). We identified the mode-of-initiation and mechanism-of-arrhythmias in this model, which accounts for arterial hypertension observed in a significant proportion of post-MI patients.
Methods and Results: Yorkshire pigs underwent aortic banding 1-month following large anterior MI, and were allowed to survive for another 2-months. Aortic banding resulted in 1.3-fold increase in systemic vascular resistance index. HF/iAL pigs presented with mildly decreased left ventricular ejection fraction without significant changes in the end-diastolic and end-systolic volume indexes. Pressure-volume relationship during the preload reduction study revealed stiffer left ventricle in the HF/iAL pigs consistent with remote non-ischemic myocardial hypertrophy found in macroscopic and histological assessment. Increased afterload in HF/iAL pigs also led to a major increase in interstitial fibrosis in non-ischemic remote areas. HF/iAL pigs were highly prone to pacing-induced VT/VF, specifically under conditions of hypokalemia. Investigation of the electrophysiological substrate revealed the dependence of hypokalemia-mediated arrhythmias on conduction rather than repolarization abnormalities. HF/iAL pigs exhibited conduction slowing down to critical levels that were not achieved in normal preparations. Altered rate-dependent kinetics of conduction slowing in HF/iAL were consistent with a higher safety margin for successful propagation of abnormally slow wavefronts that gave rise to reentrant activity.
Conclusions: Increased afterload in the post-MI heart is associated with cellular hypertrophy, widespread interstitial fibrosis, and increased ventricular stiffness. These changes predispose patients to congestive HF and promote reentrant arrhythmias during hypokalemia by facilitating the successful propagation of critically-slow wavefronts. Our findings reveal a novel mechanism by which non-K sparing diuretics promote lethal arrhythmias in hypertensive post-MI patients.
Author Disclosures: K. Ishikawa: None. C. Xie: None. L.J. Motloch: None. J. Aguero: None. J. Hu: None. L. Leonardson: None. K.M. Fish: None. R.J. Hajjar: None. F.G. Akar: None.
- © 2015 by American Heart Association, Inc.