Invited Commentary

Abstract

Progressive dilation of the left ventricle (LV) and deterioration of LV pump performance often occur after myocardial infarction (MI). A number of pharmacological or nonpharmacological interventions, or both, have been used to attenuate or even reverse these progressive adverse changes in LV geometry and function. However, mechanisms that contribute to these changes, especially the role of the changes in the material properties of the MI region, remain largely unexplored. In this article, Pilla and colleagues [1Pilla J.J. Gorman III, J.H. Gorman R.C. et al.Theoretical impact of infarct compliance on left ventricular function.Ann Thorac Surg. 2009; 87: 803-811Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar] describe a mathematical simulation for changes in hemodynamics and LV geometry as a function of changing the compliance (or stiffness) of a hypothesized MI region. The authors refer to the mathematical model as a “lumped parameter” simulation, which comprised of resistive, capacitive, and unidirectional flow (diode) components. This model was first used to simulate normal hemodynamics and LV geometry based on database records of normal ovine physiology. An important component of this model was the inclusion of a compensatory element that accounted for maintenance of stroke volume through a feedback input that altered total blood volume. Next, this model was used to simulate LV pressures and volumes while incorporating a noncontributing portion of the LV (the MI region) at a set compliance value for the MI region. The authors report that the simulated LV pressure-volume curves closely approximated recorded values in an ovine MI model. A significant finding from this model was the attenuation in LV dilation and oxygen consumption with a stiffer (noncompliant) infarct region. An important implication of this finding with respect to remodeling of the infarct region is that modification of the composition and content of the MI scar can provide a means to prevent the almost inevitable LV dilation and deterioration in pump function after MI. Moreover, these findings provide a mathematical basis for the attenuation in post-MI LV dilation that has been reported in prior studies where biocompatible scaffolding/matrix was injected into the MI region. However, it must be recognized that any mathematical model is built on a series of assumptions and that these conditions are even more difficult to apply to the heterogeneous “border” region between the viable myocardium and the MI region. It has been postulated that the differential stress and strain patterns at the transition between viable myocardium and the border zone, as well as the interface between the border zone and the MI region, likely exacerbate expansion of the MI region. The relative paucity of critical basic science detailing of myocardial material properties, in particular at the border region, precludes more comprehensive mathematical modeling of LV remodeling post-MI. An important consideration for any model is its clinical applicability or application of the model, or both, to better understand where and when a certain therapeutic modality may confer clinical benefit. For example, if a hypothesized intervention were known to provide a specific time-dependent effect on the material properties of the MI region, then this model could be implemented to determine long-term effects of the intervention on LV dilation post-MI. In this light, further validation from complementary in vivo studies in which the relationship between compliance and the extent of LV dilation post-MI are warranted. Nevertheless, the findings from the mathematical model developed by Pilla and colleagues [1Pilla J.J. Gorman III, J.H. Gorman R.C. et al.Theoretical impact of infarct compliance on left ventricular function.Ann Thorac Surg. 2009; 87: 803-811Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar] form an important first step to further understanding the role of changes in myocardial material properties and pathologic remodeling after MI. Theoretic Impact of Infarct Compliance on Left Ventricular FunctionThe Annals of Thoracic SurgeryVol. 87Issue 3PreviewAfter coronary occlusion, the infarct region loses contractile function immediately and then undergoes a progressive healing process. This causes complex and time-dependent changes in infarct material properties that have not been well described experimentally. We used a theoretic approach to assess how infarct compliance effects left ventricular (LV) size and function after myocardial infarction. Full-Text PDF