Left Ventricular Myocardial Contractility Is Depressed in the Borderzone After Posterolateral Myocardial Infarction

Abstract

Background Contractility in the borderzone (BZ) after antero-apical myocardial infarction (MI) is depressed. We tested the hypothesis that BZ contractility is also decreased after postero-lateral MI. Methods Five sheep underwent postero-lateral MI. Magnetic resonance imaging (MRI) was performed 2 weeks before and 16 weeks after MI, and left ventricular (LV) volume and regional strain were measured. Finite element (FE) models were constructed and the systolic material parameter, Tmax, was calculated in the BZ and remote myocardium by minimizing the difference between experimentally measured and calculated LV strain and volume. Sheep were sacrificed 17 weeks after MI and myocardial muscle fibers were taken from the BZ and remote myocardium. Fibers were chemically demembranated, and isometric developed force, Fmax, was measured at supra-maximal [Ca2+]. Routine light microscopy was also performed. Results There was no difference in Tmax between pre-MI and remote myocardium 16 weeks after MI. However, there was a large decrease (63.3%, p=0.005) in Tmax in the BZ when compared with the remote myocardium 16 weeks after MI. In addition, there was a significant reduction of BZ Fmax for all samples (18.9%, p=0.023). Myocyte cross-sectional area increased by 61% (p=0.021) in the BZ, but there was no increase in fibrosis. Conclusion Contractility in the borderzone is significantly depressed relative to the remote myocardium after postero-lateral MI. The reduction in contractility is due at least in part to a decrease in contractile protein function.

A Novel Method for Quantifying Smooth Regional Variations in Myocardial Contractility Within an Infarcted Human Left Ventricle Based on Delay-Enhanced Magnetic Resonance Imaging

“…We demonstrated that a linear variation in contractility within the BZ, when compared to a homogeneous BZ contractility, reduces the mean square errors between the measured and the predicted strain fields. This result was later confirmed by direct force measurements in skinned fiber preparations from infarcted sheep LVs [5,6]. This improved description of regional ventricular mechanics is critical for using patientspecific models to predict the efficacy of existing or novel surgical procedures or devices for treating ischemic cardiomyopathy [7,8].…”

“…In Ref. [6], BZ T max was significantly reduced for all samples (18.9%, p ¼ 0.0067); moreover, myocyte cross-sectional area increased by 61% (p ¼ 0.021) in the BZ, but there was no increase in fibrosis.…”

“…When Shimkunas et al [5] studied the effect of doxycycline, an inhibitor of matrix metalloproteinases, rigor stiffness, and essential light-chain phosphorylation was not reduced in BZ myocardium, suggesting that doxycycline had a protective effect on BZ contractility. Fortunately, ex vivo biaxial tissue testing is not required to quantify in vivo regional contractilities for the case of a posterobasal or posterolateral MI because the thickness of the infarcted wall segment is at least 50% of normal [3,6,13]. In the previous studies [3,6,13], we could measure 3D myocardial strain in the MI.…”

“…Fortunately, ex vivo biaxial tissue testing is not required to quantify in vivo regional contractilities for the case of a posterobasal or posterolateral MI because the thickness of the infarcted wall segment is at least 50% of normal [3,6,13]. In the previous studies [3,6,13], we could measure 3D myocardial strain in the MI. In all three of those studies, however, it was not necessary to use a nonzero T max value in the MI for the LV finiteelement models to predict strain fields as measured with tagged MRI.…”

Bioengineered Stromal Cell-Derived Factor-1α Analogue Delivered as an Angiogenic Therapy Significantly Restores Viscoelastic Material Properties of Infarcted Cardiac Muscle

“…Following a myocardial infarction (MI), scar tissue gradually replaces myocardium that is lost through a process of collagen deposition and an increase in tensile strength of the tissue [2]. Borderzone myocardium becomes hypocontractile, leading to left ventricular dilation, increased left ventricle (LV) wall stress, and a decrease in ejection fraction [3]. LV dilation perpetuates infarct expansion, adverse ventricular remodeling, and dysfunction, which ultimately leads to heart failure.…”