Nuove applicazioni degli alfa2 agonisti in medicina veterinaria

Alpha2-agonists are a class of drugs widely used in veterinary anaesthesia; moreover by means of their action on adrenoceptors that are widespread distributed in several tissues, they can be beneficial for different clinical applications. The aim of this work was to describe new applications of alpha2-agonists in veterinary medicine. In cats, high dose medetomidine is administered to perform semen collection by urethral catheterization. We have investigated the haemodynamic effects of high dose medetomidine (0.13 mg kg-1) administered to healthy male cats. Haemodynamic evaluations were performed before and after medetomidine administration and consisted of: clinical examination, blood pressure evaluation and transthoracic echocardiography. Significant hemodynamic alterations were observed, even if they were similar to that provided by lower dosages. The cats recovered without clinical alterations. Despite their cardiovascular side effects, low doses of alpha2-agonists can be beneficial for the maintenance of a good cardiovascular stability for specific conditions. In humans, dexmedetomidine helps in maintaining a good hemodynamic stability if administered for pheochromocytoma ablation. We have described the administration of dexmedetomidine for the anesthetic management of two dogs with a suspicion of pheochromocytoma undergoing adrenalectomy. Dogs received dexmedetomidine intramuscularly (0.001 mg kg-1) and dexmedetomidine and remifentanil were administered (0.0005 mg kg-1h-1 and 0.0003 mg kg-1min-1, respectively) throughout the surgery. In this study dexmedetomidine infusion together with remifentanil provided satisfactory intraoperative anesthetic and hemodynamic control in two dogs with a suspicion of pheochromocytoma. In patients undergoing craniotomy, dexmedetomidine, increasing the cerebral vascular resistance, prevents alteration of the cerebral blood flow. We have described the administration of dexmedetomidine in five Macaca fascicularis undergoing craniotomy for physiologic research. The Macaca were sedated with ketamine (8 mg kg-1) and dexmedetomidine (0.02 mg kg-1) intramuscularly. Dexmedetomidine was administered by infusion (0.012 mg kg-1h-1) throughout the procedure and provided adequate analgesia and a stable hemodynamic control in healthy Macaca.I farmaci alfa2-agonisti sono largamente utilizzati in anestesia veterinaria; inoltre, grazie alla loro azione sui recettori alpha-adrenergici, distribuiti in diversi tessuti, sono utilizzati per diverse applicazioni cliniche. L'obiettivo del presente studio è stato quello di descrivere nuove applicazioni degli alfa2-agonisti in medicina veterinaria. Nel gatto, la medetomidina somministrata ad alte dosi consente la raccolta del seme mediante cateterismo uretrale. Abbiamo valutato gli effetti emodinamici della medetomidina somministrata al dosaggio di 0.13 mg kg-1 in gatti sani. Le valutazione emodinamiche sono state eseguite prima e dopo la somministrazione di medetomidina mediante visita clinica, misurazione della pressione sistemica ed ecocardiografia transtoracica. Dallo studio sono state evidenziate alterazioni emodinamiche significative, ma simili a quelle riportate dopo somministrazione di dosi più basse. I farmaci alpha2-agonisti, nonostante le alterazioni cardiovascolari che inducono, se somministrati a basse dosi, possono contribuire al mantenimento di una buona stabilità emodinamica in condizioni cliniche specifiche. Nell'uomo, la somministrazione di dexmedetomidina in pazienti sottoposti a rimozione di un feocromocitoma contribuisce a mantenere parametri emodinamici intraoperatori stabili. Abbiamo descritto la somministrazione perioperatoria di dexmedetomidina in due cani sottoposti a surrenalectomia per un sospetto di feocromocitoma. Entrambi hanno ricevuto dexmedetomidina intramuscolo (0.001 mg kg-1) e dexmedetomidina e remifentanil sono stati somministrati in infusione (0.0005 mg kg-1h-1 e 0.0003 mg kg-1min-1, rispettivamente) per tutta la chirurgia. Il protocollo utilizzata ha permesso di mantenere un piano anestesiologico e condizioni emodinamiche stabili in due cani con sospetto di feocromocitoma. Nei pazienti sottoposti a neurochirurgia, la dexmedetomidina previene alterazioni significative del flusso cerebrale. Abbiamo descritto la somministrazione di dexmedetomidina in esemplari di Macaca fascicularis sottoposti a craniotomia. I macachi sono stati sedati con ketamina e dexmedetomidina. La dexmedetomidina è stata somministrata in infusione continua (0.012 mg kg-1h-1) per tutta la procedura e ha permesso di mantenere un'analgesia adeguata e parametri emodinamici stabili in macachi sani

Examination of myocardial electrophysiology using novel panoramic optical mapping techniques

Optical mapping of voltage signals has revolutionised the field and study of cardiac electrophysiology by providing the means to visualise changes in electrical activity at a high temporal and spatial resolution from the cellular to the whole heart level under both normal and disease conditions. The aim of this thesis was to develop a novel method of panoramic optical mapping using a single camera and to study myocardial electrophysiology in isolated Langendorff-perfused rabbit hearts. First, proper procedures for selection, filtering and analysis of the optical data recorded from the panoramic optical mapping system were established. This work was followed by extensive characterisation of the electrical activity across the epicardial surface of the preparation investigating time and heart dependent effects. In an initial study, features of epicardial electrophysiology were examined as the temperature of the heart was reduced below physiological values. This manoeuvre was chosen to mimic the temperatures experienced during various levels of hypothermia in vivo, a condition known to promote arrhythmias. The facility for panoramic optical mapping allowed the extent of changes in conduction timing and pattern of ventricular activation and repolarisation to be assessed. In the main experimental section, changes in epicardial electrical activity were assessed under various pacing conditions in both normal hearts and in a rabbit model of chronic MI. In these experiments, there was significant changes in the pattern of electrical activation corresponding with the changes in pacing regime. These experiments demonstrated a negative correlation between activation time and APD, which was not maintained during ventricular pacing. This suggests that activation pattern is not the sole determinant of action potential duration in intact hearts. Lastly, a realistic 3D computational model of the rabbit left ventricle was developed to simulate the passive and active mechanical properties of the heart. The aim of this model was to infer further information from the experimental optical mapping studies. In future, it would be feasible to gain insight into the electrical and mechanical performance of the heart by simulating experimental pacing conditions in the model

Combining Synthesis of Cardiorespiratory Signals and Artifacts with Deep Learning for Robust Vital Sign Estimation

Healthcare has been remarkably morphing on the account of Big Data. As Machine Learning (ML) consolidates its place in simpler clinical chores, more complex Deep Learning (DL) algorithms have struggled to keep up, despite their superior capabilities. This is mainly attributed to the need for large amounts of data for training, which the scientific community is unable to satisfy. The number of promising DL algorithms is considerable, although solutions directly targeting the shortage of data lack. Currently, dynamical generative models are the best bet, but focus on single, classical modalities and tend to complicate significantly with the amount of physiological effects they can simulate. This thesis aims at providing and validating a framework, specifically addressing the data deficit in the scope of cardiorespiratory signals. Firstly, a multimodal statistical synthesizer was designed to generate large, annotated artificial signals. By expressing data through coefficients of pre-defined, fitted functions and describing their dependence with Gaussian copulas, inter- and intra-modality associations were learned. Thereafter, new coefficients are sampled to generate artificial, multimodal signals with the original physiological dynamics. Moreover, normal and pathological beats along with artifacts were included by employing Markov models. Secondly, a convolutional neural network (CNN) was conceived with a novel sensor-fusion architecture and trained with synthesized data under real-world experimental conditions to evaluate how its performance is affected. Both the synthesizer and the CNN not only performed at state of the art level but also innovated with multiple types of generated data and detection error improvements, respectively. Cardiorespiratory data augmentation corrected performance drops when not enough data is available, enhanced the CNN’s ability to perform on noisy signals and to carry out new tasks when introduced to, otherwise unavailable, types of data. Ultimately, the framework was successfully validated showing potential to leverage future DL research on Cardiology into clinical standards

Use of advanced echocardiography imaging techniques in the critically ill

Background: Critical care echocardiography has become standard of care in the ICU. New technologies have been developed and have shown potential clinical utility to elucidate myocardial dysfunction not seen with conventional imaging. We sought to determine the feasibility and potential clinical benefit of these techniques in common situations seen in the ICU. Hypothesis: Advanced echo techniques would be feasible in the majority of critically ill patients and have prognostic significance, clinical utility and diagnose cardiac abnormalities, potentially in a more sensitive manner than conventional techniques. Results: (a) Speckle tracking echocardiography (STE) Left ventricle and RV analysis with STE was feasibly in ~80% of patients. More dysfunction was found using STE vs conventional analysis. RV dysfunction assessed by STE held significant prognostic relevance in those with septic shock and highlighted subtle dysfunction induced by mechanical ventilation, both in animal and human studies. (b) 3D transthoracic echocardiography (3D TTE) Despite finding 3D TTE feasible in mechanically ventilated ICU patients (LV 72% and RV 55%), it lacked necessary low variability and high precision vs standard measures. (c) Myocardial contrast perfusion echocardiography (MCPE) Assessing acute coronary artery occlusion in the ICU patient is challenging. Troponin elevation, acute ECG changes, regional wall motion analysis on echo and overall clinical acumen often lack diagnostic capabilities. MCPE was found to be feasible in the critically ill and had better association predicting acute coronary artery occlusion vs clinical acumen alone. Conclusions: STE, 3D TTE and MCPE are feasible in the majority of ICU patients. STE may show dysfunction not recognised by conventional imaging. 3D TTE for volumetric analysis is likely not suitable for clinical use at this stage. MCPE may help guide interventions in acute coronary artery occlusion

Ultrasound studies of dilated cardiomyopathy in Dobermanns and English cocker spaniels

The basic hypothesis tested in this study was that dogs with dilated cardiomyopathy have abnormal ventricular function, and that this can be detected noninvasively using M-mode, two-dimensional (2D), and Doppler echocardiography, and also by measuring myocardial ultrasonic integrated backscatter. An additional hypothesis was that different breeds of dogs affected with DCM have a different clinical course, and that differences in ventricular function between these breeds can be detected by echocardiography or integrated backscatter measurements that might account for the different prognosisThe aims of this study therefore were (1) to identify echocardiographic variables that distinguished normal dogs from dogs with DCM; (2) to identify differences in ventricular function using echocardiography between Dobermanns and English cocker spaniels with DCM; and (3) to measure ultrasonic integrated backscatter in normal dogs and in Dobermanns and Cocker spaniels with DCM.In this group of Dobermanns, median survival time was 98 days (range 16 - 508 days), whereas median survival in the cocker spaniels was 512 days (range 51 to >1388 days), with 6/11 still alive at the time of writing (p < 0.002). All the measured M-mode variables differed significantly between the normal dogs and the dogs with DCM. Compared with the Dobermanns, the cocker spaniels had significantly increased LV free wall thickening and increased LV diastolic diameter when indexed to body surface area. All the 2D echocardiographic variables were significantly different between the normal dogs and dogs with DCM when corrected for body size, but there were no significant differences between Dobermanns and cocker spaniels. Significant differences were found between normal and DCM dogs in some but not all of the Doppler echocardiographic variables. Cocker spaniels had higher mitral A wave velocities than the normal dogs, and decreased mitral E/A ratios compared with both the other groups. Dobermanns had shorter isovolumic relaxation times than the other groupsIn the second part of this study, measurements were made of ultrasonic integrated backscatter in selected regions of the left ventricle in normal dogs and dogs with DCM. Ultrasonic integrated backscatter is a measurement of the power of the ultrasound signal returned from the myocardium to the transducer. This backscattered signal reflects basic tissue properties, and exhibits dynamic variation with contractile function that may represent fundamental alterations in the shape, size and distribution of scatterers within the myocardium. Consistent cyclic variation in integrated backscatter was observed in the LV free wall and septum of the normal dogs, but this pattern was not consistently seen in the DCM dogs. Differences were not seen between the Dobermanns and cocker spaniels, although the number of cocker spaniels measured was small.In conclusion, the DCM dogs had evidence of markedly reduced systolic function compared with the normal dogs. The affected dogs had left atrial and left ventricular dilation with thinner left ventricular walls. Although there was little evidence of any difference in systolic function between the two affected breeds, there was evidence of different diastolic function, with a tendency for Dobermanns to show a restrictive pattern of transmitral filling, and cocker spaniels to show evidence of delayed relaxation. The different pattern of diastolic dysfunction in the two breeds is consistent with the prognostic value ascribed to transmitral flow patterns in human DCM patients: delayed relaxation patterns have been associated with improved survival times in man. Reduced cyclic variation of ultrasonic integrated backscatter was also seen in the dogs affected with DCM, although no differences were found between the two affected breeds

Hemodynamic Profiling in Complicated Pregnancies

In order to permit a successful pregnancy outcome, the cardiovascular system must undergo substantial changes. This thesis addresses the hemodynamics in several pregnancy complications. A general overview of normal hemodynamic adaptation to pregnancy is provided . Several techniques of non-invasive cardiovascular monitoring like transthoracic echocardiography, obstetric Doppler ultrasound, cardiac MRI and sidestream darkfield imaging for the microvascular assessment are described and validated in pregnant women. These techniques are then used to establish a hemodynamic profile in women with pregnancy complications like women requiring tocolysis , women with severe pre-eclampsia and a hypertensive crisis and women with cardiac disease. Additionally, issues concerning pregnancy and contraception in women with cardiac disease are discussed

Bayesian Deep Learning for Cardiac Motion Modelling and Analysis

Cardiovascular diseases (CVDs) remain a primary cause of mortality globally, with an estimated 17.9 million deaths in 2019, accounting for 32% of all global fatalities. In recent decades, non-invasive imaging, particularly Magnetic Resonance Imaging (MRI), has become pivotal in diagnosing CVDs, offering high-resolution, multidimensional, and sequential cardiac data. However, the interpretation of cardiac MRI data is challenging, due to the complexities of cardiac motion and anatomical variations. Traditional manual methods are time-consuming and subject to variability. Deep learning (DL) methods, notably generative models, have recently advanced medical image analysis, offering state-of-the-art solutions for segmentation, registration, and motion modelling. This thesis encapsulates the development and validation of deep-learning frameworks in the field of cardiac motion modelling and analysis from sequential cardiac MRI scans. At its core, it introduces a probabilistic generative model for cardiac motion modelling, underpinned by temporal coherence, capable of synthesising new CMR sequences. Three models are derived from this foundational probabilistic model, each contributing to different aspects. Firstly, through the innovative application of gradient surgery techniques, we address the dual objectives of attaining high registration accuracy and ensuring the diffeomorphic characteristics of the predicted motion fields. Subsequently, we introduce the joint operation of ventricular segmentation and motion modelling. The proposed method combines anatomical precision with the dynamic temporal flow to enhance both the accuracy of motion modelling and the stability of sequential segmentation. Furthermore, we introduce a conditional motion transfer framework that leverages variational models for the generation of cardiac motion, enabling anomaly detection and the augmentation of data, particularly for pathologies that are less commonly represented in datasets. This capability to transfer and transform cardiac motion across healthy and pathological domains is set to revolutionize how clinicians and researchers understand and interpret cardiac function and anomalies. Collectively, these advancements present novelty and application potentials in cardiac image processing. The methodologies proposed herein have the potential to transform routine clinical diagnostics and interventions, allowing for more nuanced and detailed cardiac assessments. The probabilistic nature of these models promises to deliver not only more detailed insights into cardiac health but also to foster the development of personalised medicine approaches in cardiology

Robotic Biomedical Device for Recovering Cardiovascular Efficiency in Paraplegic Patients

This thesis is studying on the Design and development of a biomechanical robotize IPC device to accomplish a therapeutic methodology for recovery of cardio-circulatory functions, which may be seriously impaired in paraplegic patients. This impairment is caused by the reduction of venous return, due to the missing muscular contraction in zones without innervations. Intermittent Pneumatic Compression (IPC) is a well-known technique, which can be used for several therapeutic treatments like sports recovery, lymphoedema drainage, and deep vein thrombosis prevention. An IPC device produces a definite massaging action on the limb by inflating and deflating a given number of bladders according to particular time laws. The designed IPC device in this thesis is proposed for the lower limb to recover the venous return and preventing the Deep Vein Thrombosis (DVT) in the patients. The experimental tests on the volunteer persons showed the significant improvements on the important parameters of the cardiovascular, like the stroke volume (SV), the cardiac output (CO), and the end diastolic volume of left ventricle (LVEDV). To understand the dynamic behaviour of the IPC device and to optimize its performances, the device is characterized based on the mechanical and physiological aspects and its mathematical model is simulated in Simulink-Matlab. The validation of the mathematical model is done by comparing results with the experimental one. In addition, to apply the desired pressure pattern on the limb, two control strategies based on the PID algorithm and regulating inflating time are implemented on the model. The results of the controlled model, shows about 60% improving in performances of the device as concerns the bladder pressure control. In this case the experimental test has been done and it verified the control results of the simulatio