Evaluation of Changes in the Cardiac Function before and after Transcatheter Edge-to-Edge Mitral Valve Repair in Healthy Dogs: Conventional and Novel Echocardiography

Mitral valve regurgitation is a common canine heart disease. Transcatheter Edge-to-Edge Repair (TEER) is a transcatheter, edge-to-edge mitral repair device that uses a hybrid approach. No detailed information has been published on the hemodynamic effect of TEER on cardiac function. The aim of this report is to provide a longitudinal observation of the cardiac functional changes observed after TEER implantation in normal dogs using traditional, two-dimensional speckle tracking, and color M-mode echocardiographic methods. In the current report, TEER was implanted into two healthy dogs under general anesthesia. An echocardiographic examination was performed at baseline and weekly postoperative follow-ups were conducted until the fourth week. Successful TEER implantation was achieved with a short operation time (98 and 63 min) in the two dogs. Functional mitral valve regurgitation, elevated E/e’ ratio, elevated radial strain, and stable intraventricular pressure gradients (IVPG) were observed after the operation in the dogs. Mild non progressive mitral valve stenosis was observed in both dogs. TEER is a minimally invasive method for mitral valve surgery that necessitates more clinical trials. With longitudinal observation of heart function using novel approaches, better outcomes will be expected.

Identification and Characterization of Circulating MicroRNAs as Novel Biomarkers in Dogs With Heart Diseases

Background: Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. However, studies on circulating miRNAs in dogs with various heart diseases are limited in number. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases.Materials and Methods: Circulating levels of 11 miRNAs were investigated in serum samples of 82 dogs (72 with heart diseases and 10 healthy dogs) using quantitative reverse transcription-polymerase chain reaction. The results were correlated to clinical data including echocardiographic results and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels.Results: Upregulation of cfa-miR-130b was observed in dogs with myxomatous mitral valve degeneration (MMVD) stage B, patent ductus arteriosus, and pulmonic stenosis. In dogs with MMVD stage B, cfa-miR-130b was upregulated and correlated with clinical indices. In receiver operating characteristic (ROC) analysis, cfa-miR-130b accurately distinguished dogs with diseases from healthy dogs. We also observed that cfa-miR-375 and cfa-let-7b were upregulated in dogs with concentric cardiac hypertrophy. The cfa-miR-375 was correlated with concentric hypertrophy indices and was an accurate indicator of concentric hypertrophy in ROC analysis.Conclusions: The miRNAs identified in this study may be used as novel biomarkers and possible candidates for therapeutic targets in various canine heart diseases.

Electrophysiological Effects of the Transient Receptor Potential Melastatin 4 Channel Inhibitor 4-chloro-2-(2-chlorophenoxy)acetamido) Benzoic Acid (CBA) in Canine Left Ventricular Cardiomyocytes

Transient receptor potential melastatin 4 (TRPM4) plays an important role in many tissues, including pacemaker and conductive tissues of the heart, but much less is known about its electrophysiological role in ventricular myocytes. Our earlier results showed the lack of selectivity of 9-phenanthrol, so CBA ((4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) was chosen as a new, potentially selective inhibitor. Goal: Our aim was to elucidate the effect and selectivity of CBA in canine left ventricular cardiomyocytes and to study the expression of TRPM4 in the canine heart. Experiments were carried out in enzymatically isolated canine left ventricular cardiomyocytes. Ionic currents were recorded with an action potential (AP) voltage-clamp technique in whole-cell configuration at 37 °C. An amount of 10 mM BAPTA was used in the pipette solution to exclude the potential activation of TRPM4 channels. AP was recorded with conventional sharp microelectrodes. CBA was used in 10 µM concentrations. Expression of TRPM4 protein in the heart was studied by Western blot. TRPM4 protein was expressed in the wall of all four chambers of the canine heart as well as in samples prepared from isolated left ventricular cells. CBA induced an approximately 9% reduction in AP duration measured at 75 and 90% of repolarization and decreased the short-term variability of APD90. Moreover, AP amplitude was increased and the maximal rates of phase 0 and 1 were reduced by the drug. In AP clamp measurements, CBA-sensitive current contained a short, early outward and mainly a long, inward current. Transient outward potassium current (Ito) and late sodium current (INa,L) were reduced by approximately 20 and 47%, respectively, in the presence of CBA, while L-type calcium and inward rectifier potassium currents were not affected. These effects of CBA were largely reversible upon washout. Based on our results, the CBA induced reduction of phase-1 slope and the slight increase of AP amplitude could have been due to the inhibition of Ito. The tendency for AP shortening can be explained by the inhibition of inward currents seen in AP-clamp recordings during the plateau phase. This inward current reduced by CBA is possibly INa,L, therefore, CBA is not entirely selective for TRPM4 channels. As a consequence, similarly to 9-phenanthrol, it cannot be used to test the contribution of TRPM4 channels to cardiac electrophysiology in ventricular cells, or at least caution must be applied.

Vertebral heart size and cardiosternal contact evaluation in thoracic roentgenographs of the Nigerian indigenous dog

The aim of this cross-sectional prospective radiologic study was to determine reproducible biometric ratios for cardiac assessment in the indigenous dog. Thirty healthy male and female dogs were used for the study. Sixty right and left lateral thoracic projections of the dogs were acquired. Parameters in each radiograph were objectively evaluated, namely: cardiac long and short axes in right and left lateral views. Indices generated were the vertebral heart size and the cardiosternal contact (also known as intercostal heart size). The mean values of vertebral heart size (VHS) and intercostal heart size (IHS) were: 9.82±0.08/9.70±0.10 and 3.40±0.05/3.37±0.05 for the right and left lateral radiographs, respectively. Vertebral heart size correlated strongly, positively and significantly with cardiac long and short axes while IHS showed a high, positive and significant relationship with short axis but a moderately, positively significant association with long axis. The indices determined in the study are easy to use and allow for objective investigation of the canine heart. The results of this research are clinically relevant in the diagnosis and management of cardiac anomalies. Keywords: Diagnosis, Nigerian dogs, radiology, thoracic measurements

Signal Analysis For Cardiac Electrical Activation Studies

The aim of this study is to determine if some of the characteristics of reconstructed unipolar electrograms from the noncontact mapping system can be used to detect epicardial and to differentiate it from endocardial electrical activation in a canine heart. This would help the electrophysiologist know where exactly the origin of ventricular tachycardia or the critical point in tissue is located. Following this, arrhythmia can be successfully treated by ablating that part of the tissue of the heart. Virtual electrograms were recorded while pacing the right ventricle of an open-chest dog at multiple endocardial and epicardial sites using the commercially available noncontact mapping system (EnSite Array™ Catheter 3000). The endocardial and epicardial paced virtual electrograms from the juxtaposing sites allow for analyzing systematically the differences in their morphologies. Maximal dV / dt, area under the depolarization curve and latency extracted from unipolar electrograms demonstrated significant difference between epicardial and endocardial pacing sites with a p-value of less than 0.01 in all three cases. The above features were fed to a linear discriminant analysis based classifier and high classification accuracy was achieved. Therefore, reliable criteria can be proposed to allow for discrimination of an endocardial versus epicardial origin of electrical activation. And also the endocardial and epicardial paced virtual electrograms from the juxtaposing sites allows for an estimate of the transfer function of the myocardium in different positions of the right ventricles of a canine heart. The transfer function estimation will aid in better mathematical modeling of myocardium and could be a sensitive measure of myocardial homogeneity and arrhythmic foci localization.Another study was done on a human heart. This study was to evaluate the ability of virtual electrograms to predict abnormal bipolar electrograms. We tested the hypothesis of maxdV/dt, filtering and optimized DSM threshold. This allows better identification of abnormal myocardial substrate traditionally defined by contact bipolar mapping in human RVOT.

Signal Analysis For Cardiac Electrical Activation Studies

The aim of this study is to determine if some of the characteristics of reconstructed unipolar electrograms from the noncontact mapping system can be used to detect epicardial and to differentiate it from endocardial electrical activation in a canine heart. This would help the electrophysiologist know where exactly the origin of ventricular tachycardia or the critical point in tissue is located. Following this, arrhythmia can be successfully treated by ablating that part of the tissue of the heart. Virtual electrograms were recorded while pacing the right ventricle of an open-chest dog at multiple endocardial and epicardial sites using the commercially available noncontact mapping system (EnSite Array™ Catheter 3000). The endocardial and epicardial paced virtual electrograms from the juxtaposing sites allow for analyzing systematically the differences in their morphologies. Maximal dV / dt, area under the depolarization curve and latency extracted from unipolar electrograms demonstrated significant difference between epicardial and endocardial pacing sites with a p-value of less than 0.01 in all three cases. The above features were fed to a linear discriminant analysis based classifier and high classification accuracy was achieved. Therefore, reliable criteria can be proposed to allow for discrimination of an endocardial versus epicardial origin of electrical activation. And also the endocardial and epicardial paced virtual electrograms from the juxtaposing sites allows for an estimate of the transfer function of the myocardium in different positions of the right ventricles of a canine heart. The transfer function estimation will aid in better mathematical modeling of myocardium and could be a sensitive measure of myocardial homogeneity and arrhythmic foci localization.Another study was done on a human heart. This study was to evaluate the ability of virtual electrograms to predict abnormal bipolar electrograms. We tested the hypothesis of maxdV/dt, filtering and optimized DSM threshold. This allows better identification of abnormal myocardial substrate traditionally defined by contact bipolar mapping in human RVOT.

Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study

Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and PLA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean PLA were controlled within the acceptable ranges (AP within 5 mmHg below target; PLA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2–3.8)] and PLA [3.6% (2.2–5.7)]. The system decreased MVO2 and PLA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and PLA to avoid circulatory collapse, and reduced MVO2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted.

Metabolic markers of myocardium insulin resistance in dogs with heart failure

Background: Heart failure syndrome is an aspect of primary or secondary heart disease and is associated with decompensation, formation, and activation of pathological interactions between regulation systems. This results in myocardial energy metabolism alteration. This study was carried out to defy some metabolic aspects of myocardial tissue insulin resistance (IRM) development in canine heart failure.Aim: To investigate the myocardial tissue concentration of adenosine triphosphate (ATP), glucose transporters 1 and 4, pyruvate dehydrogenase (PDH), hexokinase 2, insulin receptor (InsR), and adropin (ADR) protein and to screen metabolic changes and IRM in canine myocardium with heart failure.Methods: We studied 28 dogs of different sexes, ages, and breeds. Groups were formed according to primary pathology: apparently healthy dogs (HD, n = 6); dogs with CDVD (CDVDD, n = 8); dogs with DCM (DCMD, n = 6); and dogs with doxorubicin chemotherapy and doxorubicin-induced cardiomyopathy (DoxCMD, n = 8). Animals in the study were diagnosed for primary disease by standard methods and algorithms. Animals were euthanized due to incurable neurological disease, refractory heart failure, or by owners will. The material was obtained immediately after death, fixed in liquid nitrogen, and stored in −80°C refrigerator. Studied proteins concentrations were analyzed in a specialized research laboratory, using ELISA kits, provided by Cloud-Clone Corp.Results: ATP, GLUT1, and GLUT4 concentrations in myocardial tissue from the valvular disease group did not differ from the HD group. In CDVD, we found depression of PDH, hexokinase II (HX2), and ADR concentrations in comparison to HD. InsR was significantly lower in the CDVD and DoxCMD groups in comparison to the HD group, but in the DCM group, it was twofold higher than in the HD group. In the DCMD and DoxCMD groups, all parameters were lower than in the HD group. ATP, HX2, ADR, GLUT1, and GLUT4 were higher in the CDVD group, than in the DCM and DoxCM groups. PDH in the CDVD and DoxCM groups did not differ. PDH was depleted in the DCM to CDVD and DoxCM groups. InsR did not differ between the CDVD and DoxCM groups, but was upregulated in the DCM to CDVD and DoxCM groups.Conclusion: Development of myocardial tissue IRM is a part of the structural, functional and metabolic remodeling in dogs with heart failure of different etiology. At the late stages, we found significant changes in energy supply availability and production in the myocardium.