Left Ventricular Cavity Volume Research Articles

Factors That Impact Evaluation of Left Ventricular Systolic Parameters in Myocardial Perfusion Gated SPECT with 16 Frame and 8 Frame Acquisition Models.

Objective:Evaluating the effects of heart cavity volume, presence and absence of perfusion defect, gender and type of study (stress and rest) on the difference of systolic parameters of myocardial perfusion scan in 16 and 8 framing gated SPECT imaging.Methods:Cardiac gated SPECT in both 16 and 8 framing simultaneously and both stress and rest phases at one-day protocol was performed for 50 patients. Data have been reconstructed by filter back projection (FBP) method and left ventricular (LV) systolic parameters were calculated by using QGS software. The effect of some factors such as LV cavity volume, presence and absence of perfusion defect, gender and type of study on data difference between 8 and 16 frames were evaluated.Results:The differences in ejection fraction (EF), end-diastolic volume (EDV) and end-systolic volume (ESV) in both stress and rest were statistically significant. Difference in both framing was more in stress for EF and ESV, and was more in rest for EDV. Study type had a significant effect on differences in systolic parameters while gender had a significant effect on differences in EF and ESV in rest between both framings.Conclusion:In conclusion, results of this study revealed that difference of both 16 and 8 frames data in systolic phase were statistically significant and it seems that because of better efficiency of 16 frames, it cannot be replaced by 8 frames. Further well-designed studies are required to verify these findings.

Assessment of cardiac hemodynamics indicators in patients with arterial hypertension and non-alcoholic fatty liver disease depending on angiotensin II type 1 receptor A1166C gene polymorphism

Aim of study is to estimate the indicators of cardiac hemodynamics in patients with arterial hypertension and non-alcoholic fatty liver disease depending on angiotensin II type 1 receptor (A1166C) gene polymorphism.Materials and methods. 55 patients with arterial hypertension and non-alcoholic fatty liver disease were comprehensively examined. The study of angiotensin II type 1 receptor (A1166C) gene polymorphism was carried out by means of the polymerase chain reaction method. Accuracy of genotype frequency distribution was assessed in accordance with the Hardy-Weinberg Equilibrium (pi2 + 2 pipj + pj2 = 1).Results. In the subgroup of patients with arterial hypertension and non-alcoholic fatty liver disease with the angiotensin II type 1 receptor gene (A1166C) C/C genotype the values of end-diastolic volume exceeded by 13.45 % and 28.31 %; the end-systolic volume –by 22.41 % and 39.09 %; the end-diastolic diameter – by 10.67 % and 38.95 %; the end systolic diameter – by 15.63 % and 29.11 %; the left ventricular mass – by 11.18 % and 19.38 %, whereas the ejection fraction was lower compared to patients with the A/C and A/A genotypes, respectively (p<0.05). According to our study results, no differences in left ventricular diastolic dysfunction were found depending on angiotensin II type 1 receptor (A1166C) gene polymorphism in the examined patients.Conclusions. The C allele of angiotensin II type 1 receptor (A1166C) gene polymorphism in patients with arterial hypertension and non-alcoholic fatty liver disease is associated with the heart morphofunctional changes, namely, hypertrophy progression, left ventricular cavity size and volume enlargement and decrease in myocardial contractility.

Reduced First-Phase Ejection Fraction and Sustained Myocardial Wall Stress in Hypertensive Patients With Diastolic Dysfunction: A Manifestation of Impaired Shortening Deactivation That Links Systolic to Diastolic Dysfunction and Preserves Systolic Ejection Fraction.

Impaired shortening deactivation of cardiac myocytes could sustain myocardial contraction, preserving ejection fraction at the expense of diastolic dysfunction. We examined the relationship between first-phase ejection fraction (EF1), the fraction of left ventricular volume ejected from the start of systole to the time of the first peak in left ventricular pressure (corresponding to the time of maximal ventricular shortening) to the duration of myocardial contraction and diastolic function in patients with hypertension (n=163), and varying degrees of diastolic dysfunction. Left ventricular systolic pressure was estimated by carotid tonometry; time-resolved left ventricular cavity and wall volume were obtained by echocardiography with speckle wall tracking. Measurements were repeated after nitroglycerin, a drug known to influence ventricular dynamics, in a subsample (n=18) of patients. EF1 and time of onset of ventricular relaxation (as determined from the temporal pattern of myocardial wall stress) were independently correlated with diastolic relaxation as measured by tissue Doppler early diastolic mitral annular velocity (E', standardized regression coefficients 0.48 and -0.34 for EF1 and time of onset of ventricular relaxation, respectively, each P<0.001, irrespective of adjustment for age, sex, antihypertensive treatment, measures of afterload, and ventricular geometry) and with diastolic function measured by the ratio of transmitral Doppler early filling velocity (E) to E' (E/E', regression coefficients -0.34 and 0.34, respectively, each P<0.001). Nitroglycerin increased EF1, decreased time of onset of ventricular relaxation, and improved diastolic function (each P<0.05). Hypertensive patients with diastolic dysfunction exhibit reduced EF1 which may sustain myocardial contraction, preserving systolic ejection fraction at the expense of impaired diastolic function.

17 A case-control study with computational modelling of acute left ventricular dysfunction

Introduction The pathophysiology of acute left ventricular dysfunction after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. In this study, we carried out a case-control study of left ventricular (LV) biomechanical behaviour in vivo using an immersed boundary-finite element (IB/FE) method. Methods Cardiac magnetic resonance images were acquired from six healthy volunteers (the healthy group) and six patients with acute LV dysfunction post-acute STEMI (the MI group) with no-reflow, defined as an acute reduction in myocardial blood flow despite a patent epicardial coronary artery. The two groups were age matched. The passive and active myocardial parameters were determined from the measured in vivo data (LV cavity volume and strain) to match the LV dynamics in diastole and systole. Results Student’s t-test was used for significance test. Our results show that even though the average measured peak cuff-pressure in the MI group is much lower than the healthy group (122 ± 21 vs. 150 ± 20mmHg, p Conclusions In summary, we have shown for the first time that, compared with controls, patients with recent ST-elevation myocardial infarction exhibit increased active tension generation in combination with predictable changes in end-diastolic volume and ejection fraction. Active tension generation is a novel biomechanical index, and its clinical and prognostic significance merits further study. Funding British Heart Foundation (PG/14/64/31043)

Elevated ejection-phase myocardial wall stress in children with chronic kidney disease.

Myocardial wall stress (MWS) is thought to be the mechanical stimulus to ventricular hypertrophy. The objective of this study was to examine whether MWS is elevated in children with chronic kidney disease (CKD) who are at high risk of developing adverse cardiovascular events related to left ventricular (LV) hypertrophy. MWS, a function of left ventricular pressure, myocardial wall volume, and cavity volume, was obtained using carotid tonometry to estimate ventricular pressure and 2-dimensional transthoracic echocardiographic wall-tracking to obtain LV cavity and wall volumes. Ninety-two children (50 boys) aged 11.2±3.2 (mean±SD) years, including healthy controls (n=16), and those with CKD disease divided into 3 groups according to estimated glomerular filtration rate (mL/min per 1.73 m2) >90 (CKD 1, n=26), 60 to 90(CKD 2, n=23), and <60 (CKD≥3, n=27) were studied. There was no significant difference in age, height, weight, central or peripheral blood pressure, LV mass, or mass index in the 4 study groups. By contrast, peak, mean, and end-systolic MWS were higher in children with CKD and increased across stages of CKD (peak MWS, 338.8±18.5 and 397.5±14.3 s/cm2 in controls and CKD≥3, respectively; P=0.01). Higher systolic MWS was explained by a form of LV dysfunction whereby dynamic values of the ratio of wall volume/cavity size during systole were lower in children with CKD than in those without (P=0.001). Children with CKD exhibit blood pressure–independent LV dysfunction which results in increased systolic MWS and which may predispose to LV hypertrophy in later life.

Assessment of left ventricular volume overload: comparison of 2-D echo and cardiac MRI

Background Left ventricular cavity dimensions and volumes are useful parameters to diagnose and monitor cardiac pathologies which lead to LV volume overload. 2-D echo/ Doppler is the most commonly used imaging modality to assess LV volume overload in patients with valvular regurgitant disease. However, 2-D echo suffers from inherent limitations related to adequacy of the intercostal echo window, anatomic positioning for cavity dimensions and volumes and incomplete visualization of the entire left ventricular cavity. This study was designed to compare assessment of LV cavity dimensions and volumes by 2-D echo and cardiac magnetic resonance (CMR) techniques in patients with LV volume overload due to valvular regurgitation

A primer on the methods and applications for contrast echocardiography in clinical imaging.

Contrast echocardiography is broadly described as a variety of techniques whereby the blood pool on cardiac ultrasound is enhanced with encapsulated gas-filled microbubbles or other acoustically active nano- or microparticles. The development of this technology has occurred primarily in response to the need improve current diagnostic applications of echocardiography such as the need to better define left ventricular cavity volumes, regional wall motion, or the presence or absence of masses and thrombi. A secondary reason for the development of contrast echocardiography has been to expand the capabilities of echocardiography. These new applications include myocardial perfusion imaging for detection of ischemia and viability, perfusion imaging of masses/tumors, and molecular imaging. The ability to fill all of these current and future clinical roles has been predicated on the ability to produce robust contrast signal which, in turn, has relied on technical innovation with regards to the microbubble contrast agents and the ultrasound imaging paradigms. In this review, we will discuss the basics of contrast echocardiography including the composition of microbubble contrast agents, the unique imaging methods used to optimize contrast signal-to-noise ratio, and the clinical applications of contrast echocardiography that have made a clinical impact.

An Inverse Finite Element Method for Determining the Tissue Compressibility of Human Left Ventricular Wall during the Cardiac Cycle

The determination of the myocardium’s tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle.

Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR

Injection of Algisyl-LVR, a treatment under clinical development, is intended to treat patients with dilated cardiomyopathy. This treatment was recently used for the first time in patients who had symptomatic heart failure. In all patients, cardiac function of the left ventricle (LV) improved significantly, as manifested by consistent reduction of the LV volume and wall stress. Here we describe this novel treatment procedure and the methods used to quantify its effects on LV wall stress and function. Algisyl-LVR is a biopolymer gel consisting of Na+-Alginate and Ca2+-Alginate. The treatment procedure was carried out by mixing these two components and then combining them into one syringe for intramyocardial injections. This mixture was injected at 10 to 19 locations mid-way between the base and apex of the LV free wall in patients. Magnetic resonance imaging (MRI), together with mathematical modeling, was used to quantify the effects of this treatment in patients before treatment and at various time points during recovery. The epicardial and endocardial surfaces were first digitized from the MR images to reconstruct the LV geometry at end-systole and at end-diastole. Left ventricular cavity volumes were then measured from these reconstructed surfaces. Mathematical models of the LV were created from these MRI-reconstructed surfaces to calculate regional myofiber stress. Each LV model was constructed so that 1) it deforms according to a previously validated stress-strain relationship of the myocardium, and 2) the predicted LV cavity volume from these models matches the corresponding MRI-measured volume at end-diastole and end-systole. Diastolic filling was simulated by loading the LV endocardial surface with a prescribed end-diastolic pressure. Systolic contraction was simulated by concurrently loading the endocardial surface with a prescribed end-systolic pressure and adding active contraction in the myofiber direction. Regional myofiber stress at end-diastole and end-systole was computed from the deformed LV based on the stress-strain relationship.

Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR

Injection of Algisyl-LVR, a treatment under clinical development, is intended to treat patients with dilated cardiomyopathy. This treatment was recently used for the first time in patients who had symptomatic heart failure. In all patients, cardiac function of the left ventricle (LV) improved significantly, as manifested by consistent reduction of the LV volume and wall stress. Here we describe this novel treatment procedure and the methods used to quantify its effects on LV wall stress and function.Algisyl-LVR is a biopolymer gel consisting of Na+-Alginate and Ca2+-Alginate. The treatment procedure was carried out by mixing these two components and then combining them into one syringe for intramyocardial injections. This mixture was injected at 10 to 19 locations mid-way between the base and apex of the LV free wall in patients.Magnetic resonance imaging (MRI), together with mathematical modeling, was used to quantify the effects of this treatment in patients before treatment and at various time points during recovery. The epicardial and endocardial surfaces were first digitized from the MR images to reconstruct the LV geometry at end-systole and at end-diastole. Left ventricular cavity volumes were then measured from these reconstructed surfaces.Mathematical models of the LV were created from these MRI-reconstructed surfaces to calculate regional myofiber stress. Each LV model was constructed so that 1) it deforms according to a previously validated stress-strain relationship of the myocardium, and 2) the predicted LV cavity volume from these models matches the corresponding MRI-measured volume at end-diastole and end-systole. Diastolic filling was simulated by loading the LV endocardial surface with a prescribed end-diastolic pressure. Systolic contraction was simulated by concurrently loading the endocardial surface with a prescribed end-systolic pressure and adding active contraction in the myofiber direction. Regional myofiber stress at end-diastole and end-systole was computed from the deformed LV based on the stress-strain relationship.

A Probabilistic Patch-Based Label Fusion Model for Multi-Atlas Segmentation With Registration Refinement: Application to Cardiac MR Images

The evaluation of ventricular function is important for the diagnosis of cardiovascular diseases. It typically involves measurement of the left ventricular (LV) mass and LV cavity volume. Manual delineation of the myocardial contours is time-consuming and dependent on the subjective experience of the expert observer. In this paper, a multi-atlas method is proposed for cardiac magnetic resonance (MR) image segmentation. The proposed method is novel in two aspects. First, it formulates a patch-based label fusion model in a Bayesian framework. Second, it improves image registration accuracy by utilizing label information, which leads to improvement of segmentation accuracy. The proposed method was evaluated on a cardiac MR image set of 28 subjects. The average Dice overlap metric of our segmentation is 0.92 for the LV cavity, 0.89 for the right ventricular cavity and 0.82 for the myocardium. The results show that the proposed method is able to provide accurate information for clinical diagnosis.

Left Ventricular Global Function Index by Magnetic Resonance Imaging—A Novel Marker for Assessment of Cardiac Performance for the Prediction of Cardiovascular Events

Left ventricular (LV) function is generally assessed independent of structural remodeling and vice versa. The purpose of this study was to evaluate a novel LV global function index (LVGFI) that integrates LV structure with global function and to assess its predictive value for cardiovascular (CV) events throughout adult life in a multiethnic population of men and women without history of CV diseases at baseline. A total of 5004 participants in the Multi-Ethnic Study of Atherosclerosis underwent a cardiac magnetic resonance study and were followed up for a median of 7.2 years. The LVGFI by cardiac magnetic resonance was defined by the ratio of stroke volume divided by LV total volume defined as the sum of mean LV cavity and myocardial volumes. Cox proportional hazard models were constructed to predict the end points of heart failure, hard CV events, and a combined end point of all CV events after adjustment for established risk factors, calcium score, and biomarkers. A total of 579 (11.6%) CV events were observed during the follow-up period. In adjusted models, the end points of heart failure, hard CV events, and all events were all significantly associated with LVGFI (heart failure, hazard ratio=0.64, P &lt;0.0001; hard CV events, hazard ratio=0.79, P =0.007; all events, hazard ratio=0.79, P &lt;0.0001). LVGFI had a significant independent predictive value in the multivariable models for all CV event categories. The LVGFI was a powerful predictor of incident HF, hard CV events, and a composite end point, including all events in this multiethnic cohort.

Advancements in pressure–volume catheter technology – stress remodelling after infarction

Microconductance catheters have been successfully applied to measure left ventricular (LV) function in the mouse to assess cardiac or pharmacological interventions for a number of years. New complex admittance methods produce an estimate of the parallel admittance of cardiac muscle that can be used to correct the measurement in real time. This contrasts with existing conductance technologies that require in vivo calibration using a bolus of hypertonic saline. Here, we report the application of this emerging technology in the context of myocardial infarction and LV remodelling. Using a combination of high-resolution ultrasound and LV conductance catheters, we compared measures of LV function using an admittance system and a traditional conductance-derived pressure-volume (PV) system. We subjected C57BL/6 mice to focal myocardial ischaemia-reperfusion by transient ligation of the left anterior descending coronary artery and assessed cardiac function with different systems to determine the reliability and accuracy of these methods to distinguish between normal and dysfunctional ventricle. We demonstrate that the admittance PV system, in our hands, provides a straightforward solution for assessing LV function in mice. Using this technique in combination with other established methods, we measured LV dysfunction following coronary artery occlusion and reperfusion, which can be ameliorated using a known preconditioning agent (CORM-3), and found that functional read-outs are representative of other methods. We have found that, especially in diseased tissue, LV pressure-volume loops derived from complex admittance provide a reproducible and reliable method of determining LV function without the need for technically challenging calibration. Our data suggest that admittance records accurate/physiological LV cavity volumes when compared with other invasive methods in the same animal. This emerging technology is both effective and reproducible for measuring LV function and dysfunction in the mouse, without the need for complicated interventions to calibrate the measurements or training in a new technology. This may mark the way towards a fast and accurate assessment of murine cardiac function in normal animals and disease models.

Assessment of left ventricular systolic function in aortic stenosis and prognostic implications

This editorial refers to ‘Global longitudinal strain is a strong independent predictor of all-cause mortality in patients with aortic stenosis’ by L.G. Kearney et al ., doi:10.1093/ehjci/jes115. Left ventricular (LV) ejection fraction, most commonly assessed with two-dimensional echocardiography, is an important prognostic determinant of many cardiovascular diseases. The decision of implanting specific cardiovascular devices, such as cardiac resynchronization therapy or implantable cardioverter defibrillator, recommending valvular surgery or chemotherapy relies on the LV ejection fraction. However, the accumulating evidence shows that LV ejection fraction is an imperfect measure of LV systolic function since it simply reflects the changes in the LV cavity volume and does not take into consideration the complex architecture of the LV.1,2 The LV myocardial fibre changes the three-dimensional spatial orientation from a right-handed helix in the subendocardial region to a left-handed helix in the subepicardium.1 This counterclockwise and clockwise spiral muscle configuration results in a characteristic three-dimenisonal LV deformation with shortening in the longitudinal and circumferential directions, thickening in the radial direction, and twist in the circumferential-longitudinal plane and permits LV emptying and filling with optimal mechanical efficiency. Thus, 15% of myofibre shortening during systole results in 40% myocardial wall thickening and >60% change in the LV ejection fraction in the normal heart.3 In addition, the extracellular collagen matrix of the myocardium supporting this myofibre arrangement is key to maintain the LV shape and size. Any change in the myofibre alignment or extracellular matrix may lead to LV dysfunction. Current imaging techniques, such as diffusion tensor and tagged magnetic resonance imaging and speckle tracking, permit non-invasive evaluation of the LV spiral muscle configuration and quantification of LV shortening, thickening, and twisting deformations. Particularly, speckle tracking echocardiography permits accurate assessment of multidirectional LV …

Assessment of cardiac function in mice using ventricular catheterization and MRI derived Pressure‐Volume loops

Stroke work normalized to end diastolic volume derived from pressure‐ volume (PV) relationships is regarded as a gold standard for measurement of the contractile status. Though conductance catheters are widely used to obtain PV relationships in the heart, it does not provide accurate measurements of absolute ventricular volumes. Magnetic resonance imaging (MRI) on the other hand provides accurate measurement of Left ventricular (LV) cavity volume but does not provide absolute measurement of LV pressure. The aim of this study was to demonstrate the feasibility of obtaining MRI volume data while invasively measuring LV pressure in wild type C57BL/6 and δ sarcoglycan null (Scgd−/−). LV pressure was measured invasively using a MR compatible fluid filled pressure transducer and volume data collected simultaneously from a 7 Tesla scanner at rest and during infusion of Dobutamine. Stroke work was calculated from the integrated area within the PV loop. Stroke work of Scgd−/− decreased from 2.8±0.56 mmHg mL at rest to 1.1±0.49 mmHg mL at stress but did not change significantly in WT. Decreased stroke work in Scgd−/− mice under stress was associated with LV pressure decline which may be related to vascular abnormalities in these mice as previously reported. This study demonstrates for the first time that invasive pressure and MRI derived volume measurements can be made simultaneously in mice.

The Combined Administration of Multiple Soluble Factors in the Repair of Chronically Infarcted Rat Myocardium

The purpose of this study was to investigate a potential benefit of simultaneous administration of multiple soluble factors (SFs) in the repair of chronically infarcted rat myocardium. Rats subjected to a permanent coronary artery occlusion (myocardial infarction) received a cocktail of SF or a phosphate buffer. Four SFs, fibroblast growth factor-2 (2 μg), insulin-like growth factor-1 (1 μg), hepatocyte growth factor (2 μg), and stromal cell-derived factor-1α (0.6 μg) were injected directly into the ischemic myocardium at the onset of occlusion and subsequently at 3, 7, 14, and 21 days of surgery (intraperitoneally). Cardiac contractile function, infarct size and remodeling, and blood vessel density were studied at 4 weeks postsurgery. Infarct size, left ventricular circumference and cavity volume, thinning ratio, and expansion index were not statistically different between groups. Treatment of SF did not alter ejection fraction, compared with control. No statistical difference in total blood vessel density in the infarct zone was observed in SF versus control. In conclusion, our results that there were no enhancements in cardiac function, reductions in infarct size, improvements in remodeling, or increases in vasculature density in SF versus control do not support the study hypothesis that the combined use of multiple SF benefits the hearts with myocardial infarct.

Impact of left ventricular trabeculations and papillary muscles on measures of cavity volume and ejection fraction

Left ventricular (LV) trabeculations are typically considered LV cavity volume (i.e. ignored) when analyzing cardiac magnetic resonance (CMR) images as they are difficult to manually segment, but they are not actually part of the LV bloodpool. The treatment of papillary muscles is more variable, but they too have often been considered bloodpool.

Effects of Zoledronate in the Repair of Chronically Infarcted Rat Myocardium

Zoledronate (Zol), one of the class of bisphophonate drugs, is commonly used to treat postmenopausal osteoporosis. Treatment of liposomal bisphosphonates has been shown to worsen myocardial infarct repair in an experimental model. The purpose of this study was to investigate the effect of Zol in the repair of chronically infarcted myocardium without liposomal encapsulation to mimic the clinical setting. Zol (20 μg/kg, a dose known to treat experimental osteoporosis in rats, n = 15) was administered subcutaneously to female Sprague-Dawley rats 1 day before coronary artery ligation. Rats receiving phosphate-buffered saline (n = 12) were used as controls. Left ventricular function, infarct size, and remodeling were studied at 4 weeks postinfarction. Zol pretreatment did not affect left ventricular ejection fraction in hearts with myocardial infarction (49.5 ± 1.4% in Zol; 50.6 ± 2.1% in phosphate-buffered saline). Infarct size was similar in Zol versus untreated hearts (34.2% ± 2.9% in Zol; 33.4% ± 2.9% in phosphate-buffered saline). Left ventricular cavity volume and circumference, infarct thickness, and expansion index were comparable between the groups. To investigate a potential effect of Zol on tissue macrophage infiltration after myocardial infarction, heart specimens were harvested 48 hours postinfarction and sections were immunostained with CD68 antibody, a macrophage-specific marker. Results of macrophage immunostaining revealed that the level of tissue macrophage infiltration was similar between groups. In conclusion, administration of Zol before myocardial infarction had no adverse effects on cardiac contractile function, infarct size, or remodeling. These results suggest that treatment of Zol given before the onset of myocardial infarction does not cause worsening of infarct repair.

Effects of Zoledronate in the Repair of Chronically Infarcted Rat Myocardium

Zoledronate (Zol), a class of bisphophonate drugs, is commonly used to treat post‐menopausal osteoporosis. Treatment of liposomal bisphosphonates, a technique that is often used to deplete tissue macrophages, has experimentally shown to worsen myocardial infarct repair. The purpose of this study was to investigate the effect of Zol in the repair of chronically infarcted myocardium without liposomal encapsulation to mimic the clinical setting. Zol (20 μg/kg) was subcutaneously administered to rat 1 day prior to coronary ligation. Rats receiving phosphate‐buffered saline were utilized for experimental comparison (control). Left ventricular function and infarct size and remodeling were studied at 4 weeks post‐infarction. Zol pre‐treatment did not affect left ventricular ejection fraction in hearts with myocardial infarction (49.5 ± 1.4% in Zol; 50.6 ± 2.1% in control). Infarct size was similar in Zol‐treat versus control hearts (34.2 ± 2.9% in Zol; 33.4 ± 2.9% in control). Left ventricular cavity volume and circumference, infarct thickness, and expansion index were comparable between the groups. In conclusion, administration of Zol prior to myocardial infarction had no adverse effects on cardiac function, infarct size, and remodeling. These results suggest that treatment with Zol in patients with an increased risk of myocardial infarction is safe and does not cause worsening of infarct repair.

The combined administration of multiple soluble factors in the repair of chronically infarcted rat myocardium

The purpose of this study was to investigate a potential benefit of simultaneous administration of multiple soluble factors (SF) in the repair of chronically infarcted rat myocardium. Rats subjected to a permanent coronary artery occlusion (MI) received a cocktail of SF or a phosphate buffer. Four soluble factors, fibroblast growth factor‐2 (2 μg), insulin‐like growth factor‐1 (1 μg), hepatocyte growth factor (2 μg), and stromal cell‐derived factor‐1α (0.6 μg) were injected directly into the ischemic myocardium at the onset of occlusion and subsequently at 3, 7, 14, and 21 days of surgery (ip). Cardiac contractile function, infarct size and remodeling, and blood vessel density were studied at 4 weeks post surgery. Infarct size, left ventricular circumference and cavity volume, thinning ratio, and expansion index were not statistically different between groups. Treatment of SF did not alter ejection fraction, compared to control. No statistical difference in total blood vessel density in the infarct zone was observed in SF vs. control. In conclusion, our results showed that there were no enhancements in cardiac function, reductions in infarct size, improvements in remodeling, nor increases in vasculature density in SF vs. control. These results do not support the study hypothesis that the combined use of SF benefits the hearts with myocardial infarct.