Myocardial hypertrophy, rate of change of free wall thickness and directional components of ventricular power in man

The diastolic (Vd) and systolic volumes, the average free wall diastolic thickness (hd) and left cardiac cavity pressures were determined in 25 subjects using monoplan angiography. Ten subjects presented a normal angiogram (NA), 5 a myocardiopathy with predominant dilatation (MCD), 4 a myocardiopathy with predominant non obstructive hypertrophy (MCH), and 6 a volume overload (VO). All the subjects had a normal coronary-cineangiogram. Myocardial volume (Vw) and systolic thickness were calculated from hd and from end-diastolic and end-systolic internal dimensions. The degree of myocardial hypertrophy was estimated from the value of Vw/Vd. The directional components of the total systolic elemental power due to thickening (average radial power : Pr) and to midwall circumferential shortening (average equatorial power : Pe) were calculated for each subject. Patients with NA, with MCD and with VO presented a positive linear correlation between Pr/Pe and Vw/Vd (r = 0.90). Patients with MCH were clearly below the regression line defined by the other groups. This relationship suggests that the contribution to the total power due to the thickening component is greater with increasing cardiac hypertrophy, except in the case of subjects showing an "inappropriate" hypertrophy.     

Left ventricular systolic performance during prolonged strenuous exercise in female triathletes

BACKGROUND: The effect of prolonged strenuous exercise (PSE) on left ventricular (LV) systolic function has not been well studied in younger female triathletes. This study examined LV systolic function prior to, during and immediately following PSE (i.e., 40 km bicycle time trial followed by a 10 km run) in 13 younger (29 PlusMinus; 6 years) female triathletes. METHODS: Two-dimensional echocardiographic images were obtained prior to, at 30-minute intervals during and immediately following PSE. Heart rate, systolic blood pressure, end-diastolic and end-systolic cavity areas were measured at each time point. Echocardiographic and hemodynamic measures were also combined to obtain LV end-systolic wall stress and myocardial contractility (i.e., systolic blood pressure - end-systolic cavity area relation). RESULTS: Subjects exercised at an intensity equivalent to 90 PlusMinus; 3% of maximal heart rate. Heart rate, systolic blood pressure, systolic blood pressure - end-systolic cavity area relation and fractional area change increased while end-diastolic and end-systolic cavity areas decreased during exertion. CONCLUSIONS: PSE is associated with enhanced LV systolic function secondary to an increase in myocardial contractility in younger female triathletes.     

Maturation of end-systolic stress-strain relations in chick embryonic myocardium

The embryonic myocardium increases functional performance geometrically during cardiac morphogenesis. We investigated developmental changes in the in vivo end-systolic stress-strain relations of embryonic chick myocardium in stage 17, 21, and 24 white Leghorn chick embryos (n = 10 for each stage). End-systolic stress-strain relations were linear in all developmental stages. End-systolic strain decreased from 0.50 +/- 0.02 to 0.31 +/- 0.01 (mean +/- SE, P < 0.05), while average end-systolic wall stress was similar at 3.29 +/- 0.34 to 4.19 +/- 0.43 mmHg (P = 0.14) from stage 17 to 24. Normalized end-systolic myocardial stiffness, a load-independent index of ventricular contractility, increased from 2.98 +/- 0.19 to 6.03 +/- 0.39 mmHg from stage 17 to 24 (P < 0.05). Zero-stress midwall volume increased from 0.024 +/- 0.002 to 0.124 +/- 0.004 microl from stage 17 to 24 (P < 0.05). These results suggest that the embryonic ventricle increases normalized ventricular "contractility" while maintaining average end-systolic wall stress over a relatively narrow range during cardiovascular morphogenesis.     

Left-ventricular shape determines intramyocardial mechanical heterogeneity

Left-ventricular remodeling is considered to be an important mechanism of disease progression leading to mechanical dysfunction of the heart. However, the interaction between the physiological changes in the remodeling process and the associated mechanical dysfunction is still poorly understood. Clinically, it has been observed that the left ventricle often undergoes large shape changes, but the importance of left-ventricular shape as a contributing factor to alterations in mechanical function has not been clearly determined. Therefore, the interaction between left-ventricular shape and systolic mechanical function was examined in a computational finite-element study. Hereto, finite-element models were constructed with varying shapes, ranging from an elongated ellipsoid to a sphere. A realistic transmural gradient in fiber orientation was considered. The passive myocardium was described by an incompressible hyperelastic material law with transverse isotropic symmetry. Activation was governed by the eikonal-diffusion equation. Contraction was incorporated using a Hill model. For each shape, simulations were performed in which passive filling was followed by isovolumic contraction and ejection. It was found that the intramyocardial distributions of fiber stress, strain, and stroke work density were shape dependent. Ejection performance was reduced with increasing sphericity, which was regionally related to a reduction in the active fiber stress development, fiber shortening, and stroke work in the midwall and subepicardial region at the midheight level in the left-ventricular wall. Based on these results, we conclude that a significant interaction exists between left-ventricular shape and regional myofiber mechanics, but the importance for left-ventricular remodeling requires further investigation.     

Dependence of heart chamber dimensions and dynamics on chamber demands and myocardial properties

A heart chamber undergoes eccentric hypertrophy in response to a chronic elevation of stroke-displacement demand, and it undergoes concentric hypertrophy in response to a chronic elevation of systolic-pressure demand. Both of these adaptations, which occur in various combinations, involve two myocardial plastic properties, "stretch normalization" and "stress normalization". We have developed a model which predicts dimensions and dynamics of the left ventricle as functions of myocardial properties and of the loads to which the chamber is adapted. The model involves: a stress-normalization rule which describes how myocardial volume depends on average systolic pressure, cavity volumes and the responsiveness of growth to stress; a stretch-normalization rule which describes how the cavity volume of standard stretch relates to average end-diastolic and end-systolic volumes; and a pressure-volume-curve equation giving isometric pressures as functions of cavity volume and myocardial volume relative to standard-stretch cavity volume, and elastic properties including contractility. The model shows how the relations among average dimensions, dynamics and loads depend on myocardial properties, particularly contractility and the growth response to stress. These properties are the main determinants of myocardial performance. In addition to the load adaptations mentioned above, the model predicts eccentric hypertrophy incident to reduced contractility, chronic dilation incident to reduced growth response to stress, myocardial stricture incident to excessive growth response to stress, and concentric hypertrophy (similar to high-pressure adaptation) incident to deposition of inert material. It allows some refinements in the evaluation of myocardial performance and in the evaluation of the abnormal properties responsible for abnormal performance.     

Excessive sympathetic nervous system activity decreases myocardial contractility

The objective of this study was to determine whether myocardial contractility is depressed by intense activation of the sympathetic nervous system. A massive sympathetic discharge was produced by injecting veratrine or sodium citrate into the cisterna magna of anesthetized rabbits (n = 10). Two and one-half hr later, the hearts were isolated and their left ventricular (LV) performance evaluated and compared with the LV performance of hearts isolated from control animals (n = 10). LV performance was evaluated from steady-state peak isovolumic systolic and end-diastolic pressures that were generated at various end-diastolic volumes (LV function curves). The relationship between peak LV systolic pressure (or the average peak developed LV wall stress) and LV end-diastolic volume was rotated downward (P less than 0.01) in the hearts removed from rabbits treated with veratrine or citrate. The LV end-diastolic pressure or LV end-diastolic wall stress of these hearts was not different from control at any end-diastolic volume. The diminished ability of the experimental hearts to develop systolic pressure or wall stress suggests that intense sympathetic activation depressed contractility. Severely damaged myofibers, located largely in the subendocardium, were found in these hearts. Furthermore, the depressed contractility was not related to pulmonary edema since only 2 of 10 rabbits developed edema.     

Relation between left ventricular cavity pressure and volume and systolic fiber stress and strain in the wall.

Pumping power as delivered by the heart is generated by the cells in the myocardial wall. In the present model study global left-ventricular pump function as expressed in terms of cavity pressure and volume is related to local wall tissue function as expressed in terms of myocardial fiber stress and strain. On the basis of earlier studies in our laboratory, it may be concluded that in the normal left ventricle muscle fiber stress and strain are homogeneously distributed. So, fiber stress and strain may be approximated by single values, being valid for the whole wall. When assuming rotational symmetry and homogeneity of mechanical load in the wall, the dimensionless ratio of muscle fiber stress (sigma f) to left-ventricular pressure (Plv) appears to depend mainly on the dimensionless ratio of cavity volume (Vlv) to wall volume (Vw) and is quite independent of other geometric parameters. A good (+/- 10%) and simple approximation of this relation is sigma f/Plv = 1 + 3 Vlv/Vw. Natural fiber strain is defined by ef = In (lf/lf,ref), where lf,ref indicates fiber length (lf) in a reference situation. Using the principle of conservation of energy for a change in ef, it holds delta ef = (1/3)delta In (1 + 3Vlv/Vw).     

Cardiac dilatation and pump dysfunction without intrinsic myocardial systolic failure following chronic beta-adrenoreceptor activation

There is no direct evidence to indicate that pump dysfunction in a dilated chamber reflects the impact of chamber dilatation rather than the degree of intrinsic systolic failure resulting from myocardial damage. In the present study, we explored the relative roles of intrinsic myocardial systolic dysfunction and chamber dilatation as mediators of left ventricular (LV) pump dysfunction. Administration of isoproterenol, a beta-adrenoreceptor agonist, for 3 mo to rats (0.1 mg.kg(-1).day(-1)) resulted in LV pump dysfunction as evidenced by a reduced LV endocardial fractional shortening (echocardiography) and a decrease in the slope of the LV systolic pressure-volume relation (isolated heart preparations). Although chronic beta-adrenoreceptor activation induced cardiomyocyte damage (deoxynucleotidyl transferase-mediated dUTP nick-end labeling) as well as beta(1)- and beta(2)-adrenoreceptor inotropic downregulation (attenuated contractile responses to dobutamine and salbutamol), these changes failed to translate into alterations in intrinsic myocardial contractility. Indeed, LV midwall fractional shortening (echocardiography) and the slope of the LV systolic stress-strain relation (isolated heart preparations) were unchanged. A normal intrinsic myocardial systolic function, despite the presence of cardiomyocyte damage and beta-adrenoreceptor inotropic downregulation, was ascribed to marked increases in myocardial norepinephrine release, to upregulation of alpha-adrenoreceptor-mediated contractile effects as determined by phenylephrine responsiveness, and to compensatory LV hypertrophy. LV pump failure was attributed to LV dilatation, as evidenced by increased LV internal dimensions (echocardiography), and a right shift and increased volume intercept of the LV diastolic pressure-volume relation. In conclusion, chronic sympathetic stimulation, despite reducing beta-adrenoreceptor-mediated inotropic responses and promoting myocyte apoptosis, may nevertheless induce pump dysfunction primarily through LV dilatation, rather than intrinsic myocardial systolic failure.     

Functional alterations after cardiac sodium-calcium exchanger overexpression in heart failure

The sodium-calcium exchanger (NCX) is discussed as one of the key proteins involved in heart failure. However, the causal role and the extent to which NCX contributes to contractile dysfunction during heart failure are poorly understood. NCX overexpression was induced by infection with an adenovirus coding for NCX, which coexpressed green fluorescence protein (GFP) (AdNCX) by ex vivo gene transfer to nonfailing and failing rabbit cardiomyocytes. Myocardial gene transfer in rabbits in vivo was achieved by adenoviral delivery via aortic cross-clamping. Peak cell shortening of cardiomyocytes was determined photo-optically. Hemodynamic parameters in vivo were determined by echocardiography (fractional shortening) and tip catheter [maximal first derivative of left ventricular (LV) pressure (dP/dt(max)); maximal negative derivative of LV pressure (-dP/dt(max))]. Peak cell shortening was depressed after NCX gene delivery in isolated nonfailing and in failing cardiomyocytes. In nonfailing rabbits in vivo, basal systolic contractility (fractional shortening and dP/dt(max)) and maximum rate of LV relaxation (-dP/dt(max)) in vivo were largely unaffected after NCX overexpression. However, during heart failure, long-term NCX overexpression over 2 wk significantly improved fractional shortening and dP/dt(max) compared with AdGFP-infected rabbits, both without inotropic stimulation and after beta-adrenergic stimulation with isoproterenol. -dP/dt(max) was also improved after NCX overexpression in the failing rabbits group. These results indicate that short-term effects of NCX overexpression impair contractility of isolated failing and nonfailing rabbit cardiomyocytes. NCX overexpression over 2 wk in vivo does not seem to affect myocardial contractility in nonfailing rabbits. Interestingly, in vivo overexpression of NCX decreased the progression of systolic and diastolic contractile dysfunction and improved beta-adrenoceptor-mediated contractile reserve in heart failure in rabbits in vivo.     

The dynamics of contraction and walls motion of the calf heart left ventricle

The echocardiographic research of the left ventricular has revealed heterogeneity of thickness of the posterior wall and interventricular septum in three parallel planes in the transverse direction of the left ventricle in calves. The amplitude of systolic motion of the left ventricle posterior wall is larger than that of the interventricular septum at the level of the mitral valve, at the level of the papillary muscles, and at the apical level. The excursion of left ventricular walls in the basal level is twice as large as the mobility of ventricular walls in the apical level. During the contraction of the myocardium, the shortness of the left ventricular transversal diameter is to great extent determined by the degree of contraction of the left ventricular wall rather than of the interventricular septum. The high contractility is revealed in calves.     

Influence of left-ventricular shape on passive filling properties and end-diastolic fiber stress and strain

Passive filling is a major determinant for the pump performance of the left ventricle and is determined by the filling pressure and the ventricular compliance. In the quantification of the passive mechanical behaviour of the left ventricle and its compliance, focus has been mainly on fiber orientation and constitutive parameters. Although it has been shown that the left-ventricular shape plays an important role in cardiac (patho-)physiology, the dependency on left-ventricular shape has never been studied in detail. Therefore, we have quantified the influence of left-ventricular shape on the overall compliance and the intramyocardial distribution of passive fiber stress and strain during the passive filling period. Hereto, fiber stress and strain were calculated in a finite element analysis of passive inflation of left ventricles with different shapes, ranging from an elongated ellipsoid to a sphere, but keeping the initial cavity volume constant. For each shape, the wall volume was varied to obtain ventricles with different wall thickness. The passive myocardium was described by an incompressible hyperelastic material law with transverse isotropic symmetry along the muscle fiber directions. A realistic transmural distribution in fiber orientation was assumed. We found that compliance was not altered substantially, but the transmural distribution of both passive fiber stress and strain was highly dependent on regional wall curvature and thickness. A low curvature wall was characterized by a maximum in the transmural fiber stress and strain in the mid-wall region, while a steep subendocardial transmural gradient was present in a high curvature wall. The transmural fiber stress and strain gradients in a low and high curvature wall were, respectively, flattened and steepened by an increase in wall thickness.     

Load-sensitive measures may overestimate global systolic function in the presence of left ventricular hypertrophy: a comparison with load-insensitive measures

Transgenic animal models have provided a vital insight into the pathogenesis of cardiovascular disease, but functional cardiac assessment is often limited by high heart rates and small heart size. We hypothesized that in the presence of concentric left ventricular (LV) hypertrophy (LVH), load-sensitive measures of contractility may be misinterpreted as overestimating global cardiac function, because the normal function of excess sarcomeres may displace a greater volume of blood during contraction. Conductance catheter technology was used to evaluate pressure-volume (P-V) relationships as a load-insensitive method of assessing cardiac function in vivo in 18-wk-old heterozygous (mRen-2)27 transgenic rats (a model of LVH), compared with age-matched Sprague-Dawley (SD) controls. Anesthetized animals underwent echocardiography followed by P-V loop analysis. Blood pressure, body weight, and heart rate were higher in the Ren-2 rats (P < 0.05). Load-sensitive measures of systolic function, including fractional area change, fractional shortening, ejection fraction, and positive peak rate of LV pressure development, were greater in the Ren-2 than control animals (P < 0.05). Load-insensitive measures of systolic function, including the preload recruitable stroke work relationship and the end-systolic P-V relationship, were not different between Ren-2 and SD rats. Regional wall motion assessed by circumferential shortening velocity suggested enhanced circumferential fiber contractility in the Ren-2 rats (P = 0.02), but tissue Doppler imaging, used to assess longitudinal function, was not different between groups. Although conventional measures suggested enhanced systolic function in the Ren-2 rat, load-insensitive measures of contractility were not different between Ren-2 and SD animals. These findings suggest that the normal range of values for load-sensitive indexes of contractility needs to be altered according to the degree of LVH. To accurately identify changes in systolic function, we suggest that a combination of echocardiography with assessment of load-insensitive measures be used routinely.     

Increase in cardiac contractility during puberty

Pubertal growth of heart was analyzed. Growth rates of "diastolic variables" of heart size were compared with that of 'systolic', and both with growth intensities of some body structures and functions that are related to cardiac growth. Longitudinal echocardiographic, ergometric and anthropometric measurements were performed in 84 healthy boys, aged 11.5 years at the beginning and 14.5 at the end of study. Diastolic thickness of left ventricular walls increased by a mean rate of 15% and systolic by 36% (p < 0.001). As a result, percent systolic wall thickening increased from 20% to 41% during the 3 years (p < 0.001). Other measures of cardiac contractility increased in the same manner. Increase in measures of cardiac preload and afterload corresponds to the increase in heart "diastolic" and "systolic" variables, respectively. The study gave evidences for an increase in cardiac contractility during puberty. Coexistence of two simultaneous growth models for pubertal heart: diastolic and systolic, is suggested.     

Myocardial stress equations: fiberstresses of the prolate spheroid

There are occasions in physiological research and medical practice where it is desirable to estimate the average fiberstress in a chamber wall, knowing only the pressure and dimensions. Because the contribution of a strained wall element to pressure depends on its location whereas its contribution to average stress is independent of location, an equation of this kind must involve an assumption about the stress distribution. When applied to a particular chamber, it will give an exact result only if the chamber's stress distribution is in some sense like that of the model for which the equation was derived. Since the fibers of biological chambers are continually being deposited and resorbed, they tend to exhibit similar stretches under the average conditions of the chamber. To the extent that this is so, P = (2/3) sigma v ln V0/Vc, is the best simple fiberstress equation for biological chambers. (P = transmural pressure, sigma v = volume-averaged fiberstress, V0 = volume enclosed by outside surface, Vc = cavity volume). It expresses the pressure-dimension-average-fiberstress relation of a chamber of any shape whose stresses exhibit the simplest possible distribution. One can add a term to the right side to account for the influence of stress profile complexities. That term takes the form of a moment whose value is zero at one state of distension. This "stress moment" expresses the unequal weighting of complexities on the two sides of the midwall isobar. Judging from the sarcomere length profile of the left ventricular wall, the stress moment is zero and the average fiberstress equation above is exact for average developed stress (without a second term) when cavity volume is somewhere near end-diastolic. Moreover, the departures from the relation (the effects of stress moment) are small so long as the inner and outer stresses do not differ by a factor greater than two.     

Right ventricular dysfunction following acute myocardial infarction in the absence of pulmonary hypertension in the mouse

Background

Cardiac remodelling after AMI is characterized by molecular and cellular mechanisms involving both the ischemic and non-ischemic myocardium. The extent of right ventricular (RV) dilatation and dysfunction and its relation to pulmonary hypertension (PH) following AMI are unknown. The aim of the current study was to evaluate changes in dimensions and function of the RV following acute myocardial infarction (AMI) involving the left ventricle (LV).

Methods

We assessed changes in RV dimensions and function 1 week following experimental AMI involving the LV free wall in 10 mice and assessed for LV and RV dimensions and function and for the presence and degree of PH.

Results

RV fractional area change and tricuspidal annular plane systolic excursion significantly declined by 33% (P = 0.021) and 28% (P = 0.001) respectively. Right ventricular systolic pressure measured invasively in the mouse was within the normal values and unchanged following AMI.

Conclusion

AMI involving the LV and sparing the RV induces a significant acute decline in RV systolic function in the absence of pulmonary hypertension in the mouse indicating that RV dysfunction developed independent of changes in RV afterload.     

Heart size-independent analysis of myocardial function in murine pressure overload hypertrophy

Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress (sigma)-strain (epsilon) relations in normal and hypertrophied mice. LV volume was measured using two pairs of miniature omnidirectional piezoelectric crystals implanted orthogonally in the endocardium and one crystal placed on the anterior free wall to measure instantaneous wall thickness. Highly linear sigma-epsilon relations were obtained in control (n = 7) and hypertrophied mice produced by 7 days of transverse aortic constriction (TAC; n = 13). Administration of dobutamine in control mice significantly increased the load-independent measure of LV contractility, systolic myocardial stiffness. In TAC mice, systolic myocardial stiffness was significantly greater than in control mice (3,156 +/- 1,433 vs. 1,435 +/- 467 g/cm(2), P < 0.01), indicating enhanced myocardial contractility with pressure overload. However, despite the increased systolic performance, both active (time constant of LV pressure decay) and passive (diastolic myocardial stiffness constant) diastolic properties were markedly abnormal in TAC mice compared with control mice. These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload.     

Fractional precipitation for paclitaxel pre-purification from plant cell cultures of Taxus chinensis

Fractional precipitation is a simple and efficient procedure for pre-purification of paclitaxel. The optimal methanol composition in water, paclitaxel content in crude extract, storage temperature, and time were 61.5% (v/v), 0.5% (w/v), 0°C, and 3 days, respectively. As purity of the paclitaxel in the crude extract increases, the purity and yield of paclitaxel from fractional precipitation increases. This pre-purification process serves to minimize the solvent usage, size and complexity of the HPLC operations for paclitaxel purification. This process is readily scalable to a pilot plant and eventually to a production environment where multikilogram quantities of material are expected to be produced.     

The dependence of chamber dynamics on chamber dimensions

One can learn something about the determinants of ventricular dimensions and dynamics from a simple spherical model. We have derived equations showing how isometric pressure, compliance, isometric P-V curves and viscous resistance to wall displacement depend on dimensions of a spherical chamber whose fibers adjust for a "normal" stretch at a particular point in the pump cycle. The derivations show: (a) that isometric pressure at this point is proportional to the logarithm of total chamber volume (cavity plus wall) relative to cavity volume; (b) that compliance at this point is proportional to cavity volume and to total chamber volume relative to wall volume; (c) that the rate of wall displacement relative to the disparity between isometric pressure and actual pressure depends on dimensions like compliance depends on dimensions; and (d) since reciprocal compliance does not increase with wall/cavity ratios as much as isometric pressure at the normal-stretch volume, the P-V curves spread out on either side of the normal-stretch volume as the chamber undergoes adaptive thickening, resulting in disproportionate increases of isometric pressure at low cavity volumes. This tends to increase ejection fraction and reduce cavity volumes relative to stroke volume, and it is partly responsible for the "concentric" character of hypertrophy in response to high systolic pressure.     

Time course of changes in the expression of DHPR, RyR2, and SERCA2 after myocardial infarction in the rat left ventricle

Postinfarction left ventricular remodeling leads to the functional decline of the left ventricle (LV). Since dihydropyridine receptor (DHPR), ryanodine receptor (RyR₂), and sarco-endoplasmic reticulum (SR) Ca²⁺-ATPase2 (SERCA2a) play a major role in the contractility of the heart, the aim of our study was to evaluate the time course of changes in the expression of these proteins 1 day, 2 weeks and 4 weeks after myocardial infarction (MI). Myocardial infarction was produced by ligation of left anterior descending coronary artery of the rat. Transthoracic echocardiography was performed to characterize structural and functional changes after MI. To evaluate protein mRNA levels and the relative amount of proteins, real-time quantitative RT-PCR and Western blotting were used. LV ejection fraction and fractional shortening decreased significantly during the 4-week follow-up period (P < 0.001). Typical features of LV remodeling after MI were seen, with a decrease in anterior wall thickness (P < 0.001) and dilatation of the LV (P < 0.001). Expression of DHPR and RyR₂ mRNAs decreased and Serca2a mRNA tended to decrease 1 day after MI (P < 0.001, P < 0.01 and P = 0.06, respectively), followed by recovery of the expression during the next 4 weeks. In the infarcted hearts the quantities of SERCA2 proteins in the LV were significantly decreased at the time of 4 weeks. In conclusion, MI was associated with transient decrease in the expression of the DHPR and RyR₂ mRNAs and a reduced quantity of SERCA2 proteins in the LV. Since they have a key role in the contraction of the heart, changes in the expression of these proteins may be important regulators of LV systolic function after MI.     

A novel method for quantifying in-vivo regional left ventricular myocardial contractility in the border zone of a myocardial infarction

Homogeneous contractility is usually assigned to the remote region, border zone (BZ), and the infarct in existing infarcted left ventricle (LV) mathematical models. Within the LV, the contractile function is therefore discontinuous. Here, we hypothesize that the BZ may in fact define a smooth linear transition in contractility between the remote region and the infarct. To test this hypothesis, we developed a mathematical model of a sheep LV having an anteroapical infarct with linearly-varying BZ contractility. Using an existing optimization method (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," J. Biomech. Eng., 131(11), pp. 111001), we use that model to extract active material parameter T(max) and BZ width d(n) that "best" predict in-vivo systolic strain fields measured from tagged magnetic resonance images (MRI). We confirm our hypothesis by showing that our model, compared to one that has homogeneous contractility assigned in each region, reduces the mean square errors between the predicted and the measured strain fields. Because the peak fiber stress differs significantly (~15%) between these two models, our result suggests that future mathematical LV models, particularly those used to analyze myocardial infarction treatment, should account for a smooth linear transition in contractility within the BZ.