Reply to “Letter to the editor: Characterizing preclinical model of ischemic heart failure: difference between LAD and LCx infarctions”

Abstract

REPLY: We thank Dr. Katz and colleagues (7) for their interest and comments on our recent study (3). The study was conducted to develop and characterize a large animal model of chronic heart failure (HF) associated with large myocardial infarction (MI).In the six-lead electrocardiography, ST-segment elevation was observed in all the animals, usually in the lateral electrodes, in both the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx) MIs. In addition, as shown in Fig. 3 (3), all the infarctions had similar transmurality, which is not likely to be found in non-ST-segment elevation MI.In terms of the scar size, we believe the question arose from the different methods to analyze this index. While Katz et al. probably consider the scar size as a percent surface area, we calculated it as a percent volume of the left ventricle (LV). Infarct expansion occurs in both circumferential and longitudinal directions, while there is a significant thinning in the radial direction. Therefore, even though the scar increases in surface area, scar volume decreases (11). Additionally, scar volume relative to total LV myocardial volume further decreases as the remote myocardium becomes more hypertrophic. We estimated the scar/myocardium volumes by planimetry of the short-axis cross sections. Although we do not have MRI data on scar size at this time, our method shows a strong relationship to the measured scar/myocardium weight in explanted hearts.We fully agree with the comments by Katz et al. that dP/dt max is highly dependent on hemodynamic conditions and load-independent measures of contractility would add more information. In fact, we found significant differences in echocardiographic longitudinal strain among the groups, which is considered a less load-dependent indicator of systolic function (2). We would like to emphasize, however, that the important message from the similar dP/dt max in LCx MI and shamoperated animals is that this parameter is one of many performance parameters that need to be considered together rather than individually, especially in ischemic cardiac disease, in which there is heterogeneity of myocardial contractility. Consistent with the present finding, we have previously demonstrated that LV ejection fraction was a better indicator than dP/dt max to indicate the presence of systolic dysfunction in post-MI pigs (4).One of the major aims in our study was to develop a large-animal model of HF that mimics HF in ischemic patients who require novel therapeutic approaches. Thus achieving advanced LV remodeling was one of our goals in developing this model. Presumably in sheep based on their publications, Katz et al. report that their animals experience HF symptoms after LCx MI that require daily diuretics and ␤-blocking agents. In contrast, we did not observe such HF symptoms in LCx MI pigs, whereas a few pigs after LAD MI died from HF. The difference in HF severity is likely because of the development of ischemic mitral regurgitation after LCx MI in sheep. Llaneras et al. (1...

Reduced longitudinal contraction is associated with ischemic mitral regurgitation after posterior MI

“…Scar area relative to the remaining myocardium was measured by digital planimetry. No significant differences were found in the ratio of scar to myocardium area (LCx group: 12.0 Ϯ 4.1%, LCx ϩ D1 group: 14.3 Ϯ 2.4%, and OM ϩ D1 group: 12.3 Ϯ 2.8%), likely attributed to a different degree of scar tissue thinning and remodeling of the noninfarcted myocardium (18). In general, the addition of D1 infarcts on top of the LCx infarcts resulted in increased infarct areas at the posterolateral wall toward the papillary muscle periphery (Fig.…”