Although strategies have focused on myocardial salvage/regeneration in the context of an acute coronary syndrome and a myocardial infarction (MI), interventions targeting the formed MI region and altering the course of the post-MI remodeling process have not been as well studied. This study tested the hypothesis that localized high-frequency stimulation instituted within a formed MI region using low-amplitude electrical pulses would favorably change the trajectory of changes in left ventricle geometry and function.Methods
At 7 days following MI induction, pigs were randomized for localized high-frequency stimulation (n = 5, 240 bpm, 0.8 V, and 0.05 ms pulses) or unstimulated (n = 6). Left ventricle geometry and function were measured at baseline (pre-MI) and at 7, 14, 21, and 28 days post-MI using echocardiography. MI size at 28 days post-MI was determined by histochemical staining and planimetry.Results
At 7 days post-MI and before randomization to localized high-frequency stimulation, left ventricular ejection fraction and end-diastolic volume was equivalent. However, when compared with 7-day post-MI values, left ventricle end-diastolic volume increased in a time-dependent manner in the MI unstimulated group, but the relative increase in left ventricle end-diastolic volume was reduced in the MI localized high-frequency stimulation group. For example, by 28 days post-MI, left ventricle end-diastolic volume increased by 32% in the MI unstimulated group but only by 12% in the MI localized high-frequency stimulation group (P < .05). Whereas left ventricular ejection fraction appeared unchanged between MI groups, estimates of pulmonary capillary wedge pressure, a marker of adverse left ventricle performance and progression to failure, increased by 62% in the MI unstimulated group and actually decreased by 17% in the MI localized high-frequency stimulation group when compared with 7-day post-MI values (P < .05). MI size was equivalent between the MI groups, indicative of no difference in the extent of absolute myocardial injury.Conclusions
The unique findings from this study are 2-fold. First, targeting the MI region following the resolution of the acute event using a localized stimulation approach is feasible. Second, localized stimulation modified a key parameter of adverse post-MI remodeling (dilation) and progression to heart failure. These findings demonstrate that the MI region itself is a modifiable tissue and responsive to localized electrical stimulation.