Both high energy transthoracic and direct epicardial defibrillation can result in RV and LV myocardial damage, but little is known about the damage due to defibrillation using an endocardial RV electrode. Furthermore, disturbances in postdefibrillation oxidative metabolism have been reported and may be caused by primary injury of mitochondrial integrity and function, but information about ultrastructural mitochondrial alterations is rare. We therefore studied, in 13 fox hounds, RV and LV ultrastructural alterations following multiple low energy endocardial countershocks. Using an ICD and an endocardial defibrillation system a median of 54 (43-74) countershocks with a cumulative energy of 1,558 J (844-2,141 J) was delivered. After termination of countershocks, RV and LV myocardium was examined by electron microscopy. In both ventricles, severe myocardial alterations were found, including swollen mitochondria, disruption of mitochondrial crests, and loss of integrity of the mitochondrial inner and outer membranes. At the first time a semiquantitative score, originally developed for postischemic injury, was successfully used to grade the postcountershock mitochondrial alteration, which showed a more pronounced damage in the RV (2.69 +/- 0.22 points) compared to the LV (2.18 +/- 0.22 P = 0.021). We conclude that even the use of endocardial lead systems with low energy countershocks may lead to severe mitochondrial damage, especially in the RV.