Normal Left Ventricular Myocardium Research Articles

Left and right ventricular strain using fast strain-encoded cardiovascular magnetic resonance for the diagnostic classification of patients with chronic non-ischemic heart failure due to dilated, hypertrophic cardiomyopathy or cardiac amyloidosis

AimsTo compare the ability of left ventricular (LV) and right ventricular (RV) strain measured by fast-strain encoded cardiovascular magnetic resonance (CMR) (fast-SENC) with LV- and RV-ejection fraction for the diagnostic classification of patients with different stages of chronic heart failure (stages A-D based on American College of Cardiology/American Heart Association guidelines) due to non-ischemic cardiomyopathies.MethodsOur study population consisted of 276 consecutive patients who underwent CMR for clinical reasons, and 19 healthy subjects. Wall motion score index and non-infarct related late gadolinium enhancement (LGE), LV ejection fraction (LVEF) and RV ejection fraction (RVEF) and global LV- and RV-longitudinal (GLS) and circumferential strain (GCS) based on fast-SENC acquisitions, were calculated in all subjects. The percentage of LV and RV myocardial segments with strain ≤ − 17% (%normal LV and RV myocardium) was determined in all subjects.ResultsLVEF and RVEF, LV-GLS, LV-GCS, RV-GLS, RV-GCS and %normal LV- and RV myocardium depressed with increasing heart failure stage (p < 0.001 for all by ANOVA). By multivariable analysis, %normal LV and RV myocardium exhibited closer associations to heart failure stages than LVEF and RVEF (rpartial = 0.79 versus rpartial = 0.21 for %normal LV myocardium versus LVEF and rpartial = 0.64 versus rpartial = 0.20 for %normal RV myocardium versus RVEF, respectively). Furthermore, %normal LV and RV myocardium exhibited incremental value for the identification of patients (i) with subclinical myocardial dysfunction and (ii) with symptomatic heart failure, surpassing that provided by LVEF and RVEF (ΔAUC = 0.22 for LVEF and ΔAUC = 0.19 for RVEF with subclinical dysfunction, and ΔAUC = 0.19 for LVEF and ΔAUC = 0.22 for RVEF with symptomatic heart failure, respectively, p < 0.001 for all). %normal LV myocardium reclassified 11 of 31 (35%) patients judged as having no structural heart disease by clinical and imaging data to stage B, i.e., subclinical LV-dysfunction.ConclusionsIn patients with non-ischemic cardiomyopathy, %normal LV and RV myocardium, by fast-SENC, enables improved identification of asymptomatic patients with subclinical LV-dysfunction. This technique may be useful for the early identification of such presumably healthy subjects at risk for heart failure and for monitoring LV and RV deformation during pharmacologic interventions in future studies.

Preparation of Nano Zinc Particles and Evaluation of Its Application in Mouse Myocardial Infarction Model.

Nanometer zinc particles were synthesized by orthogonal test with manganese chloride, iron chloride and zinc sulfate as raw materials and NaOH as coprecipitating agent. The optimum synthesis conditions of coprecipitation method were obtained and the samples were characterized by various means. In this experiment, the SV, EF, FS, lvaws, lvawd, lvpws and lvpwd of left ventricle in mice with myocardial infarction were decreased, while the LVEDd, lveds and lvevs were increased in the environment exposed to ultrafine zinc nanoparticles, which proved that exposure to ultrafine zinc nanoparticles could lead to the enlargement of left ventricle, the thinning of ventricular wall, and the decrease of cardiac systolic and diastolic function. Further study on the heart tissue sections showed that the normal left ventricular myocardium of mice exposed to ultrafine zinc nanoparticles decreased, apoptotic cells increased, collagen content increased significantly, and myocardial fibrosis intensified. At the same time, WGA staining results of myocardial cell membrane showed that inhalation of ultra-fine nano zinc particles increased the size of myocardial infarction cells and disordered cell arrangement, which further proved that inhalation of ultra-fine nano zinc particles accelerated left ventricular pathological remodeling. The results of this study prove that the ultra-fine zinc nanoparticles in the air play an important role in the structural remodeling of myocardial infarction heart, and provide a theoretical basis for formulating targeted policies to control air pollution.

The approaches to prevention and therapy of cardiovascular disorders in children with chronic bronchopulmonary pathology

The purpose of this study was to develop and evaluate the algorithm for cardiovascular disorders prevention and therapy effectiveness in children with chronic bronchopulmonary pathology. Materials and methods. There was catamnestic examination of 57 patients with chronic bronchopulmonary pathology (29 children with severe, controlled or partially controlled persistent bronchial asthma and 28 children with cystic fibrosis and pancreatic insufficiency) who were analyzed the dynamics of left ventricular myocardial remodeling, depending on the administrated treatment. Catamnesis duration was 1 year. The average age of children in the observation group was 9.2 ± 0.6 years. The ultrasound examination of the heart was performed using the Medison SonoAce 8000 ultrasound machine (USA) according to the standard procedure. The mathematical analysis and statistical processing of data were performed on a PC using the licensed software package of Statistic for Windows 10.RU using variation, correlation, regression and nonparametric methods of statistical analysis. Variables were expressed as M ± m and P value <0.05 was considered to indicate statistical significance. Results . It has been established that there is a structural and functional left ventricular myocardium rearrangement on the background of left ventricular diastolic dysfunction development, sympathetic branch of the autonomic nervous system functional impairment, myocardium electrical instability and endothelium-depended vasodilation disturbance in children with chronic bronchopulmonary diseases. The algorithm has been worked out for choosing tactics of cardiovascular disorders therapy based on the study results, which is a complex of non-medicamentous and medicamentous methods with drug modulators of – nitric oxide system – ACE and L-arginine inhibitors inclusion in the therapy. The effectiveness of proposed algorithm was estimated in 27 children with chronic bronchopulmonary diseases. The other 30 patients, who were treated with traditional therapy, made up a comparison group. It has been found that proposed therapeutic method application in the complex treatment of children with chronic bronchopulmonary pathology contributed to left ventricular myocardium morphofunctional state improvement by slowing processes of left ventricular remodeling and increasing the number of patients who had normal left ventricular myocardium geometry. There was a progression of the left ventricle morphofunctional state changes in the comparison group, which was manifested by an increase in the left ventricular myocardium mass and structural-geometric myocardial restructuring by concentric type of cardiac remodeling. Conclusions. The use of proposed algorithm can prevent cardiovascular disorders progression and provide more effective rehabilitation of children with chronic bronchopulmonary diseases.

Application of ripple mapping to visualize slow conduction channels within the infarct-related left ventricular scar.

Ripple mapping (RM) displays each electrogram at its 3-dimensional coordinate as a bar changing in length according to its voltage-time relationship with a fiduciary reference. We applied RM to left ventricular ischemic scar for evidence of slow-conducting channels that may act as ventricular tachycardia (VT) substrate. CARTO-3© (Biosense Webster Inc, Diamond Bar, CA) maps in patient undergoing VT ablation were analyzed on an offline MatLab RM system. Scar was assessed for sequential movement of ripple bars, during sinus rhythm or pacing, which were distinct from surrounding tissue and termed RM conduction channels (RMCC). Conduction velocity was measured within RMCCs and compared with the healthy myocardium (>1.5 mV). In 21 maps, 77 RMCCs were identified. Conduction velocity in RMCCs was slower when compared with normal left ventricular myocardium (median, 54 [interquartile range, 40-86] versus 150 [interquartile range, 120-160] cm/s; P<0.001). All 7 sites meeting conventional criteria for diastolic pathways coincided with an RMCC. Seven patients had ablation colocating to all identified RMCCs with no VT recurrence during follow-up (median, 480 [interquartile range, 438-841] days). Fourteen patients had ≥1 RMCC with no ablation lesions. Five had recurrence during follow-up (median, 466 [interquartile range, 395-694] days). One of the 2 patients with no RMCC locations ablated had VT recurrence at 605 days post procedure. RMCCs were sensitive (100%; negative predictive value, 100%) for VT recurrence but the specificity (43%; positive predictive value, 35.7%) may be limited by blind alleys channels. RM identifies slow conduction channels within ischemic scar and needs further prospective investigation to understand the role of RMCCs in determining the VT substrate.

Absolute values of late enhancement volume is superior to percentage of late enhancement volume per total LV myocardium volume to predict MACE in hypertrophic cardiomyopathy: a CMR Study

Purpose: To determine a useful predictor of major adverse cardiac events (MACE) in patients with hypertrophic cardiomyopathy (HCM), we compared focal late enhancement (LE) volume (LEV) in the left ventricular myocardium (LVM) to the percentage of LEV per total LVM volume (TLVMV) (%LEV/TLVMV) by cardiac magnetic resonance (CMR), and followed subjects for a median of 16 months. Methods: Fifty-five consecutive HCM subjects (33 males, mean age 62.5±13.6 years) undergoing CMR (1.5T Intra achieva, Philips) were recruited. CMR was acquired at 15 min after injection of Gadopentetate dimeglumine for detecting LEV in LVM quantitatively. Areas with signal-intensity ≥ mean+2SD of signal-intensity of remote normal LVM were regarded as LE. LEV was measured by the threshold method (Ziostation 2, Zio). Result: LE in LVM was detected in 46 subjects, and LEV and %LEV/TLVMV were 35.4±27.1cm3 and 25.0±19.2%, respectively. Ten subjects (18%) had MACE. According to Receiver Operating Characteristic (ROC) curves, at a cutoff of 45.6cm3 (LEV) and 23.8% (%LEV/TLVMV), the sensitivity and specificity of LEV for MACE detection were 80% and 75%, respectively (Area under curve (AUC) 0.766) and those of %LEV/TLVMV were 100% and 59% (AUC 0.811), respectively. HCM subjects were divided into groups on the basis of 1) LEV ≥ and <45.6cm3 and (2) %LEV/TLVMV ≥ and <23.8%. Significant differences between Group 1 and Group 2 subjects were observed on Kaplan Meier analysis and log rank test (both P<0.01). On Cox proportional hazard models, the hazard ratios for the occurrence of MACE were 8.08 (LEV, P=0.008) and 60.8 (%LEV/TLVMV, P=0.118), and only the former was significant. ![Figure][1] ROC curves Conclusion: Both LEV and %LEV/TLVMV by CMR may be useful to predict the risk of MACE in HCM subjects, and LEV is superior to %LEV/TLVMV. [1]: pending:yes

Detection and quantification of myocardial perfusion defects by resting single-phase 64-slice cardiac computed tomography angiography compared with SPECT myocardial perfusion imaging

Hypoenhanced regions on cardiac computed tomography angiography (CCTA) correlate with myocardial hypoperfusion. We evaluated the ability of resting single-phase 64-slice CCTA to detect the presence of myocardial infarction (MI) compared with nuclear myocardial perfusion imaging (MPI). One hundred and forty symptomatic patients (age 66±12 years, 64% men) with an irreversible perfusion defect (n=69) or a normal/reversible perfusion defect (n=71) on MPI were subjected to CCTA for further evaluation. MI on CCTA was detected visually on the basis of areas of hypoattenuation (dark) in the myocardium and the corresponding Hounsfield Units (HU) were measured. CCTA accurately detected MI in 62 patients with an irreversible perfusion defect on MPI, yielding a sensitivity of 90%, a specificity of 94%, a negative predictive value of 91%, and a positive predictive value of 94%. The mean HU of normal and infarcted left ventricular myocardium was 107±23 and 16±40, respectively (P<0.001). An HU cut-off of 28 detected the presence of myocardial scar with 86% sensitivity and 59% specificity. The infarct volume measured by CCTA correlated well with the summed rest score (r=0.567; P<0.001) and the summed stress score (r=0.489; P<0.001) on MPI. In a substudy of 50 patients, the GE perfusion tool yielded a sensitivity of 92%, a specificity of 73%, an negative predictive value of 91%, and a positive predictive value of 76% in detecting MI. Resting single-phase CCTA is highly accurate in detecting and quantifying MI. This study highlights a novel clinical utility of CCTA in addition to assessment of plaque burden and stenosis with no risk of additional radiation or contrast exposure to the patient.

Troponin T and Plasma Collagen Peptides in Heart Failure

The extracellular matrix of the heart is made up of a number of structural proteins including fibrillar collagen, smaller amounts of elastin, laminin, fibronectin, and signaling peptides. The complex collagen 3-dimensional weave, mainly consisting of type I collagen, interconnects individual myocytes through a collagen–integrin–cytoskeletal–myofibril arrangement.1 This network supports cardiac myocytes during contraction and relaxation and also provides a mechanism for translating individual myocyte shortening and force generation into ventricular contraction. It is also responsible for much of the ventricle’s passive diastolic stiffness.2 In both human and animal studies, progressive left ventricular remodeling and dysfunction are associated with significant changes in the extracellular matrix.3–5 Article see p 406 The structural hallmark of prolonged pressure-overload hypertrophy is increased collagen accumulation between individual myocytes and myocyte fascicles (Figure 1).6,7 Thus, the highly organized architecture of the extracellular matrix undergoes significant alterations in collagen structure, composition, and geometry caused by increased collagen synthesis, postsynthetic processing, posttranslational modification, and decreased degradation and turnover. This “reactive” collagen deposition is characterized by both perivascular and interstitial fibrosis.2,8,9 The changes in collagen homeostasis that occur during the development of chronic pressure-overload hypertrophy are directly associated with increased myocardial diastolic stiffness properties, which in turn cause abnormal diastolic filling.7,10,11 Indeed, clinical evidence suggests that progressive extracellular matrix accumulation and diastolic dysfunction are important underlying pathophysiological mechanisms for heart failure in patients with pressure-overload hypertrophy.12,13 Figure 1. Scanning electron micrographs taken from normal nonhuman primate left ventricular myocardium following the induction of pressure-overload hypertrophy (POH). These microscopic studies demonstrated thickening of the collagen weave and overall increased relative content between myocytes with POH. Reproduced with permission.6 In volume-overload hypertrophy because of the persistently elevated preload, a much different pattern of extracellular …

Distinguishing focal fibrotic lesions and non-fibrotic lesions in hypertrophic cardiomyopathy by assessment of regional myocardial strain using two-dimensional speckle tracking echocardiography: Comparison with multislice CT

PurposeTo distinguish focal fibrotic and non-fibrotic lesions in left-ventricular myocardium (LVM) in hypertrophic-cardiomyopathy (HCM)-subjects, we compared myocardial regional peak-strain values using two-dimensional speckle-tracking transthoracic-echocardiography (TTE) in multislice computed-tomography (CT)-detected fibrotic, non-fibrotic and normal control lesions. MethodsTwenty subjects (10 consecutive HCM-subjects (8-males, mean 63.4-years), 10 healthy controls (5-males, mean 51.5-years)) underwent speckle-tracking TTE (iE-33), and analysis of regional peak-longitudinal (LS) and radial-strain (RS), and corresponding strain rates in each of 17 LVM segments (American-Heart-Association classification). In HCM-subjects, fibrotic lesions were identified by early-phase defective enhancement and late-phase abnormal enhancement by CT (Light-Speed-Ultra-16). Regional peak LS and RS at basal, mid and apical levels were measured in MSCT-detected fibrotic and non-fibrotic LVM lesions. ResultsIn 10 HCM subjects, 143 lesions (84.1%) yielded good tracking on TTE. Twenty lesions showed fibrotic changes in 5 subjects by CT.Regional peak-LS and RS absolute values were significantly lower in both fibrotic and non-fibrotic lesions in HCM subjects than in controls at basal, mid, apical levels (all P<0.05). While peak-LS (%) absolute values were significantly lower in fibrotic than non-fibrotic lesions at basal, mid and apical levels (all P<0.05), regional peak-RS absolute values were significantly lower only at mid levels. LS was a more sensitive indicator than the corresponding rate, with better reproducibility. ConclusionsIn HCM, regional peak-LS was significantly lower in fibrotic than non-fibrotic lesions in LVM by CT. Regional peak-LS by speckle-tracking provides useful information noninvasively to distinguish fibrotic from non-fibrotic lesions in LVM in HCM and normal LVM in healthy controls.

The significance of pore microarchitecture in a multi-layered elastomeric scaffold for contractile cardiac muscle constructs

Multi-layered poly(glycerol-sebacate) (PGS) scaffolds with controlled pore microarchitectures were fabricated, combined with heart cells, and cultured with perfusion to engineer contractile cardiac muscle constructs. First, one-layered (1L) scaffolds with accordion-like honeycomb shaped pores and elastomeric mechanical properties were fabricated by laser microablation of PGS membranes. Second, two-layered (2L) scaffolds with fully interconnected three dimensional pore networks were fabricated by oxygen plasma treatment of 1L scaffolds followed by stacking with off-set laminae to produce a tightly bonded composite. Third, heart cells were cultured on scaffolds with or without interstitial perfusion for 7 days. The laser-microablated PGS scaffolds exhibited ultimate tensile strength and strain-to-failure higher than normal adult rat left ventricular myocardium, and effective stiffnesses ranging from 220 to 290 kPa. The 7-day constructs contracted in response to electrical field stimulation. Excitation thresholds were unaffected by scaffold scale up from 1L to 2L. The 2L constructs exhibited reduced apoptosis, increased expression of connexin-43 (Cx-43) and matrix metalloprotease-2 (MMP-2) genes, and increased Cx-43 and cardiac troponin-I proteins when cultured with perfusion as compared to static controls. Together, these findings suggest that multi-layered, microfabricated PGS scaffolds may be applicable to myocardial repair applications requiring mechanical support, cell delivery and active implant contractility.

Multimodality Noninvasive Imaging for Assessment of Congenital Heart Disease

Major advances in the field of pediatric cardiology and cardiac surgery over the last several decades have led to a dramatic improvement in survival rates for most forms of congenital heart disease (CHD). For example, hypoplastic left heart syndrome, a previously lethal defect, now has early survival rates up to 90% at major centers.1 These improved outcomes have produced a growing population of survivors with complex CHD who are now reaching adulthood (Figure 1). During this period, improvements in surgical and medical treatments have been accompanied by developments in diagnostic modalities. Echocardiography has replaced catheterization as the primary diagnostic modality, and it is now uncommon for newborn infants to undergo catheterization for purely diagnostic purposes. Although echocardiography remains the bedrock of noninvasive cardiac imaging, the array of diagnostic modalities and techniques available continue to grow and this has spawned the specialty of “noninvasive cardiac imaging” and the need for the “cardiac imager” to be adept in all the different modalities. Figure 1. Percentage of patients under the age of 1 year (grey bars) and over the age of 18 years (black bars) undergoing echocardiography at Children’s Hospital Boston from 1983 through 2006. Note the reverse trends of these age groups reflecting the steady increase in the proportion of adult patients with congenital heart disease. Although the absolute number of infants undergoing echocardiography during this time period has increased, their proportion has steadily declined. Echocardiography, cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT) are the primary modalities used for noninvasive cardiac imaging in patients with CHD. Nuclear scintigraphy is used in selected circumstances. The Table summarizes the strengths and weaknesses of each modality. Figure 2 shows temporal trends in utilization for the various noninvasive cardiac imaging techniques at our center. It is clear that echocardiography is the most frequently …

The influence of fat thickness on the human epicardial bipolar electrogram characteristics: measurements on patients undergoing open-heart surgery

Reference values exist for endocardial but not for epicardial (EPI) substrate mapping in cases of cardiomyopathy-associated ventricular tachycardia. We sought to establish such values for EPI electrogram voltage, including areas with overlying fat. Ten patients (six males) undergoing cardiac surgery were studied. After opening the pericardium, the distal bipole of an electrophysiology catheter was placed tangential to the EPI surface to obtain an electrogram recording. The bipole was tangentially rotated 90 degrees and the higher of the two amplitudes (mV) was taken as the local amplitude. Recordings were taken from normal left and right ventricular myocardium (n = 26 data points each), over thick (> or = 0.5 cm) fat at both ventricular bases (n = 16) and thin (<0.5 cm) fat at the mid-ventricular level (n = 32). A total of 100 recordings (mean 10/patient) were analysed. Four patients underwent valvular surgery, three bypass surgery, and three combined procedures. Mean age was 61.7 +/- 10.4 years and mean left ventricular ejection fraction was 46 +/- 12%. Electrogram amplitude was inversely related to EPI fat thickness. Over thick fat, 31% of recordings were <0.5 mV. Human EPI electrogram amplitude varies by ventricular chamber and significantly by EPI fat thickness. A cut-off of 0.5 mV to define 'scar' will include normal areas with thick overlying fat. EPI substrate maps should include data on EPI fat thickness for higher specificity.

Mechanisms of Preejection and Postejection Velocity Spikes in Left Ventricular Myocardium

Normal left ventricular myocardium demonstrates distinct spikes in the velocity trace before and after left ventricular ejection. We tested the hypothesis that the preejection and postejection velocity spikes reflect early systolic shortening and late systolic lengthening that are interrupted by mitral and aortic valve closure, respectively. In 11 anesthetized dogs, timing of valve closure was determined by pressure variables; left ventricular dimensions were determined by sonomicrometry. Myocardial shortening started 20+/-10 ms (mean+/-SD; P<0.001) before mitral valve closure and was interrupted at the time of mitral valve closure (time difference, 4+/-7 ms). Similarly, myocardial lengthening started 31+/-15 ms (P<0.001) before aortic valve closure and was interrupted at the time of aortic valve closure (time difference, 0+/-3 ms). Prevention of mitral (n=4) and aortic (n=4) valve closure by stenting the valves abolished the preejection and postejection velocity spikes, respectively. Echocardiographic measurements of patients (n=15) with severe mitral regurgitation showed that the preejection velocity spike was reduced after prosthetic valve replacement (43+/-25 versus 32+/-15 mm/s; P=0.036), indicating that preejection shortening was larger with a leaking valve. Similarly, late systolic lengthening was reduced in patients (n=15) with severe aortic regurgitation after prosthetic valve replacement; minimum postejection velocity spike was increased from -32+/-11 to -17+/-11 mm/s; P=0.0003). Asynchronous onset of contraction/relaxation and atrioventricular interaction were investigated as alternative mechanisms of the velocity spikes in dogs and patient groups but were found implausible. This study supports the hypothesis that normal left ventricular preejection and postejection velocity spikes are attributed to valve closures that interrupt early systolic shortening and late systolic lengthening, respectively.

736 Mechanism behind pre- and postejection velocity spikes in normal left ventricular myocardium

s S123 Eur J Echocardiography Abstracts Supplement, December 2006 736 Mechanism behind preand postejection velocity spikes in normal left ventricular myocardium E.W. Remme 1 ; O.A. Smiseth 1 ; T. Helle-Valle 1 ; A. Opdahl 1 ; E. Pettersen 1 ; T. Vartdal 1 ; T. Edvardsen 1 ; E. Lyseggen 1 1Rikshospitalet-Radiumhospitalet Medical Center, Cardiology (Ifkf) Dept., Oslo, Norway Background: The velocity trace of normal left ventricular (LV) wall motion has distinct waves corresponding to the different phases of the cardiac cycle. However, there are two unexplained velocity spikes in the trace one just before and one just after the ejection wave. We hypothesize that the preand postejection velocity spikes are due to early-systolic shortening and late-systolic lengthening that is interrupted by mitral (MVC) and aortic valve closure (AVC), respectively. Methods and results: LV longand short-axis diameters were measured by sonomicrometry in 11 anesthetised dogs. Myocardial shortening started prior to MVC (21±10 ms). There was excellent agreement between MVC and interruption of the initial shortening during early systole (4±7 ms) where the interruption was defined as peak deceleration of shortening. Onset of lengthening preceded AVC by (31±15 ms). Interruption of the late systolic lengthening, defined as peak deceleration of lengthening, corresponded (0±3 ms) to AVC. We further investigated if abolishing aortic and mitral valve closure by stenting the valves would eliminate the preand postejection velocity spikes in separate experiments. Stenting of the mitral valve essentially abolished the preejection velocity spike, and stenting the aortic valve essentially abolished the postejection velocity spike. In a group of 10 healthy individuals LV longitudinal and radial shortening were measured by speckle tracking echocardiography. Peak deceleration of the early systolic shortening coincided (2±14 ms) with MVC, while peak deceleration of late systolic lengthening coincided (5±12 ms) with AVC. Conclusion: This study support the hypothesis that the normal LV preand postejection velocity spikes are attributed to mitral and aortic valve closure that temporarily interrupt early systolic shortening and late systolic lengthening, respectively.

Comparison of 99mTc-sestamibi/18FDG DISA SPECT with PET for the detection of viability in patients with coronary artery disease and left ventricular dysfunction

Dual-isotope simultaneous acquisition (DISA) single-photon emission computed tomography (SPECT) is an attractive technique as it permits assessment of both myocardial glucose metabolism and perfusion within a single session, but few data on its accuracy for the assessment of viability are available as yet. In the present study, DISA SPECT was compared with positron emission tomography (PET) for the detection of myocardial viability in normal and dysfunctional left ventricular (LV) myocardium. Fifty-eight patients with chronic coronary artery disease and LV dysfunction (LV ejection fraction 33+/-12%) were studied. Patients underwent a 1-day dipyridamole stress 99mTc-sestamibi/18F-fluorodeoxyglucose (18FDG) DISA SPECT and 13N-ammonia/18FDG PET protocol. Within 1 week, resting MRI was performed to assess contractile function. Comparison of PET and SPECT data was performed using both visual and quantitative analysis. The correlation of normalised activities of the flow tracers 99mTc-sestamibi and 13N-ammonia was good (r = 0.82; p < 0.001). The correlation between the two 18FDG studies was also good (r = 0.83; p < 0.001). The agreement for the assessment of viability for all segments between DISA SPECT and PET was 82%, with a kappa-statistic of 0.59 (95% CI 0.53-0.64), without a significant difference; in dysfunctional segments only, the agreement was 82%, with a kappa-statistic of 0.63 (95% CI 0.56-0.70), without a significant difference. When the DISA SPECT data were analysed visually, the agreement between DISA SPECT and PET was 83%, with a kappa-statistic of 0.58 (95% CI 0.52-0.63), without a significant difference. Moreover, there was no significant difference between visual and quantitative DISA SPECT analysis for the detection of viability. This study shows an overall good agreement between 99mTc-sestamibi/18FDG DISA SPECT and PET for the assessment of myocardial viability in patients with severe LV dysfunction. Quantitative or visual analysis of the SPECT data did not influence the agreement with PET, suggesting that visual assessment may be sufficient for clinical purposes.

Gene expression and in situ localization of diacylglycerol kinase isozymes in normal and infarcted rat hearts: effects of captopril treatment.

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attenuator of the PKC activity. In rats, five DGK isozymes have been cloned, but little is known about their role in the heart. In this study, the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybridization histochemistry and immunohistochemistry. In normal left ventricular myocardium, DGKalpha, DGKepsilon, and DGKzeta mRNAs were expressed evenly throughout the myocardium, although the DGKalpha expression was very low. In infarcted hearts, the expression of DGKzeta was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKzeta expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKepsilon in the infarcted and border areas was lower than that in the viable left ventricle (LV) throughout the postoperation period. Furthermore, DGKepsilon expression in the viable myocardium 21 days after MI decreased significantly compared with left ventricular myocardium in the sham-operated rats and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.

Hemodynamic Effects of Antiarrhythmic Compounds: Intrinsic Effects and Autonomic Modulation

Besides their proarrhythmic side-effects, most antiarrhythmic drugs exert varying degrees of depressant action on hemodynamics, which may limit their utility, especially in patients with compromised left ventricular function. Antiarrhythmic drugs have not only myocardial inotropic effects but also act on the coronary and peripheral circulation and the heart rate. Thus, sophisticated and appropriate experimental conditions are necessary to define the effect of their direct negative inotropic actions versus their circulatory effects and the impact of drug-induced autonomic modulation. This study describes an extended comparison of amiodarone, d-sotalol, d,l-sotalol, and dofetilide as class III antiarrhythmic drugs with the actions of several class I antiarrhythmic drugs in an open-chest model. The experimental model permits not only measurements in the intact circulation but also measurements of isovolumic indexes of contractility, which are independent of drug-induced changes in ventricular preload and afterload. Furthermore, after autonomic blockade, hemodynamic effects can be measured independently of modulatory adrenergic effects in such a model. d-Sotalol and amiodarone had cardiodepressant effects only at doses significantly higher than the highest doses used clinically. Dofetilide did not have a negative inotropic effect at doses up to 40 ng/kg. However, these results might be modified in experimental models with severely compromised left ventricular function, as was shown for class I antiarrhythmic drugs and for d,l- and d-sotalol. The sensitivity to a drug’s negative inotropic action is markedly increased in functionally impaired myocardium. Furthermore, in a model of postischemic myocardial dysfunction, the depressant effect of d-sotalol could largely be avoided by previous autonomic blockade, indicating the importance of the residual β-blocking potency of d-sotalol in the doses used in our experiments. Thus, in clinically relevant doses amiodarone, d-sotalol, and dofetilide were found to be devoid of negative inotropic actions in the setting of normal left ventricular myocardium. In failing hearts, such effects become more readily evident than they do in normal hearts after high doses of amiodarone and d-sotalol. From β-blocking experiments in hearts with left ventricular dysfunction, it could be inferred that residual β-blocking and other negative inotropic mechanisms may produce a net negative inotropic action, thus masking the minor positive class III effects postulated from in vitro experiments. These observations may have significant clinical implications, because they suggest that the intrinsic myocardial effects of antiarrhythmic drugs may be modified by autonomic effects, the status of ventricular function, and changes in preload and afterload.

Measurement of angiotensin II: Use of two injectors to minimize HPLC shadowing

We investigated the use of two HPLC injectors, one reserved for standards and the other for blanks or biological samples, to minimize shadowing in the measurement of angiotensin II (ANGII). HPLC carryover of standard ANGII to blank with a one-injector and a two-injector system were 47.0 ± 5.0 and 2.4 ± 0.5 fmol/ml , respectively, a 19.6-fold reduction. Measured normal canine left ventricular myocardium ANGII level by the two-injector HPLC-RIA system was 22.3 ± 2.4 fmol/g , with a signal-to-noise ratio of 11.7, an improved signal-to-noise ratio of 29.3 fold vs. the one injector. This innovation reduced the incidence of false-positive ANGII results, and thus can be applied to other compounds that exhibit HPLC-derived shadowing.

Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts.

Gap junctions are a determinant of myocardial conduction. Disturbances of gap-junctional content may account for abnormalities of impulse propagation, contributing to the arrhythmic tendency and mechanical inefficiency of ischemic and hypertrophied myocardium. The aim of this study was to characterize gap junction organization in normal human ventricular myocardium and to establish whether abnormalities exist in myocardium of chronically ischemic and hypertrophied hearts. Cardiac gap-junctional connexin43 antibodies and confocal microscopy were used in a quantitative immunohistochemical study of surgical myocardial samples to explore the structural basis of electromechanical ventricular dysfunction in chronic ischemic and hypertrophic heart diseases. Normal adult human left ventricular myocardium had a gap-junctional surface area of 0.0051 micron2/micron3 myocyte volume; gap junctions were confined to intercalated disks, of which there was a mean of 11.6 per cell. The right ventricle showed similar gap junction surface area. Left ventricular myocardium from ischemic hearts (distant from any fibrotic scarring), despite normal numbers of intercalated disks per cell, had a reduced gap junction surface area (0.0027 micron2/micron3; P = .02), as did hypertrophied myocardium (0.0031 micron2/micron3; P = .05). The cardiac myocytes in the pathological tissues were larger than normal, and estimated gap-junctional content per cell was reduced in ischemic ventricle (P = .02) compared with normal. Gap junctions in normal adult human working ventricular myocardium occupy an area of 0.0051 micron2/micron3 myocyte volume. This surface area is reduced in ventricular myocardium from hearts subject to chronic hypertrophy and ischemia, despite a normal number of intercellular abutments, and this alteration may contribute to abnormal impulse propagation in these hearts.

New interpretation of systolic time intervals from active cross-bridge model.

Using an active cross-bridge model proposed by the authors, it has been established theoretically that cross-bridge activation rate (Ka) of the left ventricular myocardium, which might correspond to the rate of binding of Ca2+ with troponin C, is approximately expressed as a simple formula: Ka = 3/electromechanical systole (sec-1), although no definitive biological proof has yet been provided for the equation. One hundred eighteen patients without significant cardiac disease and 6 patients who had atrioventricular block with a permanent pacemaker were evaluated to determine the Ka value of the normal human left ventricular myocardium (test 1), and to examine the effect of changes in heart rate (test 2) as well as afterloading (test 3) or dobutamine infusion (test 4) on Ka. The pacing rate was increased from 50 to 110 beats/min at 20-beat increments in test 2. Arterial pressure was elevated by angiotensin II infusion in test 3, and 7 subjects received a continuous dobutamine infusion in test 4. The Ka value was found to be related to heart rate, to be increased by dobutamine infusion, and to be decreased by myocardial lengthening due to afterloading. Dependence of Ka on heart rate appeared to result from changes in myocardial length. The Ka value corrected for heart rate (Kac) had an average variation of only 4.6%, and was unrelated to age or myocardial length in individual subjects. Thus, the Kac value of normal human left ventricular myocardium appears to be nearly constant between individuals but to be increased by catecholamine infusion or myocardial shortening.

Sodium-pump injury and arrhythmogenic transient depolarizations in catecholamine-induced cardiac hypertrophy

The pathogenesis of arrhythmogenic transient depolarizations (TDs) was studied by means of electrophysiological and cytochemical methods in normal and hypertrophied left ventricular myocardium of the rat. In hypertrophy induced by administration of 5 mg/kg isoprenaline once daily for 7 days, the myocardial membrane was depolarized, the action potential duration was prolonged and the V̇ max was decreased, as compared with those of age-matched normal controls. TDs induced by a train of action potentials could be observed in hypertrophied myocardium, but not in normal control myocardium. Ryanodine completely abolished TDs, but the β-adrenoceptor agonist noradrenaline and the adenylate cyclase activator forskolin were without effect. In cytochemical studies, the Na +,K +-ATPase activity was localized in the sarcolemma, and three times as much reaction product, which appeared on the inner side of the cell membrane, was found in the normal myocardium than in the hypertrophied myocardium. The results suggest that catecholamine-induced cardiac hypertrophy damages the membrane-bound Na +,K +-ATPase and causes a cAMP-independent intracellular Ca overload and TDs, thereby permitting abnormal impulse formation, which predisposes the diseased myocardium to develop arrhythmias.