<p>Knowledge of the leftventricular (LV) pressure-volume relation, along withparameters derived from this relation, have led to newpossibilities for the characterisation of cardiac pumpfunction, in both experimental studies and clinicalsettings.</p><p>The pressure-volume diagram is apowerful tool for visualising LV performance, but in order tobe clinically useful it is necessary to make plots continuouslyand on-line. The conductance catheter technique offers thispossibility. The conductance catheter system has experiencedgrowing interest among cardiologists, physiologists, surgeons,and anaesthesiologists around the world as a powerful newresearch tool, but the invasiveness of this technique has beena limiting factor for most clinical applications. The catheterneeds to be thinner and softer in order to make this techniquemore suitable for human use.</p><p>This thesis reports of a newthin and soft conductance catheter for continuously and on-linemeasurements of LV pressure and volume.</p><p>One way to reduce both cathetersize and stiffness is to decrease the number of electrodes onthe catheter. Theoretical calculations shown in this thesisproves that it is possible to obtain the same performance witha single segment catheter as with a five-segment catheter. Thethin catheter has been tested and compared to a commercialfive-segment conductance catheter in animal studies.</p><p>We conclude that the thin singlesegment conductance catheter can measure left ventricularvolume and pessure. The regression coefficient between the twomethods is good independent of loading condition and duringbaseline conditions the catheters produce very similar volumecurves. During preload reduction the estimated volume reductionis different in the two systems.</p><p>Our thin catheter does notdisturb the heart's normal electrophysiology, neither by thecatheter current nor by any mechanical stimuli. The resultsdemonstrates that our thin, soft, single segment conductancecatheter has performance characteristics which warrant furtherdevelopment, with the goal to make the method available forhuman use.</p>

The design, fabrication, and in-vivo testing of an implantable device to measure the pressure-volume (PV) relationship in the hearts of conscious, untethered rats is presented. Volume is measured using a tetrapolar catheter positioned in the left-ventricle which emits a 20kHz current field across the LV blood pool and parallel heart tissue and measures the resulting voltage. The admittance method is used to instantaneously remove the contribution of the parallel heart muscle and Wei’s non-linear blood conductance-to-volume equation is used to calculate volume. Pressure is measured with a strain gauge sensor at the tip of the catheter. The implant was designed to be small, light, and low-power. An average implant occupies 5 cm3, weighs 8g, and on a single charge collects data for 2 months taking 43 samples per day. Collected data is transmitted wirelessly via RF to a base station where it is recorded. The functionality of the implant and measurement system was verified in six rat experiments. In all experiments, ambulatory PV loops were measured on implantation day. Viable pressure data was recorded for 11 days in one rat; in another rat viable admittance data was collected for 10 days. Changing catheter position and non-constant blood resistivity are considered as sources of error in the volume measurement. Pressure drift due to changing atmospheric pressure is considered as a source of error in the pressure measurement. Lastly, alternative uses for the implant and directions for future improvement are considered. / text

Knowledge of the leftventricular (LV) pressure-volume relation, along withparameters derived from this relation, have led to newpossibilities for the characterisation of cardiac pumpfunction, in both experimental studies and clinicalsettings. The pressure-volume diagram is apowerful tool for visualising LV performance, but in order tobe clinically useful it is necessary to make plots continuouslyand on-line. The conductance catheter technique offers thispossibility. The conductance catheter system has experiencedgrowing interest among cardiologists, physiologists, surgeons,and anaesthesiologists around the world as a powerful newresearch tool, but the invasiveness of this technique has beena limiting factor for most clinical applications. The catheterneeds to be thinner and softer in order to make this techniquemore suitable for human use. This thesis reports of a newthin and soft conductance catheter for continuously and on-linemeasurements of LV pressure and volume. One way to reduce both cathetersize and stiffness is to decrease the number of electrodes onthe catheter. Theoretical calculations shown in this thesisproves that it is possible to obtain the same performance witha single segment catheter as with a five-segment catheter. Thethin catheter has been tested and compared to a commercialfive-segment conductance catheter in animal studies. We conclude that the thin singlesegment conductance catheter can measure left ventricularvolume and pessure. The regression coefficient between the twomethods is good independent of loading condition and duringbaseline conditions the catheters produce very similar volumecurves. During preload reduction the estimated volume reductionis different in the two systems. Our thin catheter does notdisturb the heart's normal electrophysiology, neither by thecatheter current nor by any mechanical stimuli. The resultsdemonstrates that our thin, soft, single segment conductancecatheter has performance characteristics which warrant furtherdevelopment, with the goal to make the method available forhuman use. / NR 20140805

The prevalence of cardiovascular disease in the United States dramatically increases with age. A hallmark feature of the aged myocardium is increased fibrosis resulting in diastolic dysfunction. Moreover, the survival of patients subsequent to a myocardial infarction is inversely related to age because of a certain extent to maladaptive remodeling mediated by cardiac fibroblasts. Our hypothesis is that cardiac fibroblast (CF) dysfunction results in overexpressed TGF-β1 leading to increased cardiac collagen content in the aged population. TGF-β1 stimulates the synthesis of the extracellular matrix proteins, including collagen in the cardiac tissues. The RT-PCR analysis of mRNA expression of TGF-β1 of the CF was increased by 43% in the aged mice as compared to the younger. The stiffness of the left ventricle is expressed with the slope of the end-diastolic pressure-volume relationship parameter, β (mmHg/μL). In a mouse model, we demonstrated that β was 0.30 ± 0.05 in the young as compared to 0.52 ± 0.10 in the aged (p < .05). The ventricular stiffness was associated with the myocardial collagen content; namely, young versus the aged was 9.5 ± 4.0 as compared to 16.4 ± 2.3% of total protein, respectively (p < .05). In conclusion, the gene structure-function relationships support our hypothesis that cardiac fibroblast disregulation contributes to diastolic filling dysfunction in elderly persons. These data provide a potential contributory mechanism for diastolic dysfunction that may be vital in caring for the aged open-heart surgical patient.

Partie I : Objectifs. Ce travail propose une étude anatomique du coeur de porc afin d’élaborer des recommandations pour la réalisation d’une chirurgie cardiaque expérimentale. Matériels et méthodes. 16 porcs ont été étudiés. Le réseau coronaire artériel a été étudié chirurgicalement (n=13) et angiographiquement (n=10). Le réseau veineux coronaire a été analysé par dissections anatomiques (n=13) et injections rétrogrades de bleu de méthylène via le sinus coronaire (n=8). Résultats. Le positionnement intrapéricardique spécifique du coeur de porc, limite l’accès à l’aorte ascendante et à l’oreillette droite et nécessite des précautions particulières pour la réalisation d’une sternotomie et d’une canulation de l’aorte ascendante avec cardioplégie antérograde par la racine de l’aorte. Le réseau coronaire artériel est comparable au réseau humain (réseau droit dominant: 70%). Le sinus coronaire reçoit 4 afférences contre 3 chez l’homme. L’étude de la distribution de surface du réseau veineux nécessite la ligature préalable de la veine azygos gauche et confirme une asymétrie de perfusion au détriment du VD. La paroi antérieure du VD étant drainée par des petites veines cardiaques indépendantes du sinus coronaire. Conclusions. La connaissance des spécificités anatomiques cardiaques du porc a permis d’établir des recommandations pour la réalisation du modèle d’autorétroperfusion myocardique et plus largement de procédures chirurgicales cardiaques expérimentales sécurisées. Partie II : Objectifs. La perfusion rétrograde dans le sinus coronaire est utilisée pour la diffusion d’une solution de cardioplégie. Nous avons développé un modèle porcin d’autorétroperfusion myocardique à coeur battant (SMR) utilisant le réseau veineux coronaire pour assurer l’oxygénation du myocarde ventriculaire gauche. Ce modèle nous a permis d’évaluer les réponses hémodynamiques et cardiaques induites par SMR avant et après occlusion de l’artère IVA. Matériels et Méthodes. Une dérivation entre l’aorte ascendante et le sinus coronaire a été mise en place pour assurer une perfusion rétrograde sélective de la grande veine coronaire en sang oxygéné (SMR). Un groupe Contrôle (n=6) a permis de collecter des données physiologiques de référence et un groupe SMR (n=6) a été spécifiquement dédié à l’évaluation du concept d’autorétroperfusion myocardique après occlusion de l’artère IVA pendant au moins 240 minutes. Le débit cardiaque (CO), la pression maximale intra-VG (Pmax in-LV), le volume éjecté (SV), la fraction d’éjection ventriculaire gauche (FEVG), la durée diastolique (DD), la fréquence cardiaque (HR) et la pression artérielle systémique ont été monitorés en continu durant la période d’autorétroperfusion au moyen d’un cathéter de conductance type Millar® avant et après occlusion de l’IVA. La qualité de la perfusion systémique périphérique a été évaluée par l’analyse de la microcirculation sublinguale. En fin de procédure, les coeurs étaient prélevés pour une analyse histologique. Résultats. L’évaluation échographique de la FEVG était biaisée par la sternotomie alors que celle réalisée par le cathéter de conductance ne l’était pas. Le débit cardiaque après sternotomie a chuté en moyenne de 7.51% (P < 0.05). L’autorétroperfusion avec artère IVA perméable a généré des effets inotropes positifs, caractérisés par une augmentation du CO, du SV, de la Pmax in-LV et de la FEVG (P <0.0001). Après occlusion de l’IVA, l’autorétroperfusion a assuré, durant 240 minutes, une oxygénation myocardique et une compensation hémodynamique garantissant la préservation de la perfusion périphérique. L’analyse histologique a confirmé l’absence d’infarctus myocardique. Conclusions. L’autorétroperfusion myocardique a confirmé des propriétés inotropes positives et protectrices contre l’ischémie ouvrant des perspectives d’applications intéressantes / Part I: Objectives. This work reports an anatomic study of swine heart in order to produce technical recommendations and achieve successful experimental cardiac surgical procedures. Methods. 16 swines were studied. Coronary artery vessels were surgically (n=13) and angiographically (n=10) assessed. Coronary venous vessels were studied by anatomic dissections (n=13) and retrograde injection of methylene blue through the coronary sinus (n=8). Results. Specific pericardial positioning of swine heart dramatically differs from human heart resulting in a limited access to ascending aorta and right atrium, requiring surgical precautions to perform a safe sternotomy and canulation of ascending aorta with an antegrade cardioplegia. Arterial coronary pattern is similar to that of humans (right dominant supply: 70%). Pig coronary sinus receives 4 main branches vs 3 in human sinus. Preliminary ligation of the left azygos vein is required to visualize the surface distribution of methylene blue within the venous vessels, thereby confirming an optimized perfusion of the left ventricle whereas the right ventricle remains poorly perfused. This asymmetry of perfusion results from a specific venous drainage of the right ventricle through small cardiac veins disconnected from coronary sinus. Conclusions. Anatomic knowledge of swine heart validated surgical guidelines for designing the model of self-myocardial retroperfusion and safely performing experimental cardiac surgical procedures. Part II: Background. Retrograde perfusion into the coronary sinus is used to deliver cardioplegia. We developed an in-vivo porcine beating-heart model of self-myocardial retroperfusion (SMR) using the venous route to supply myocardial oxygenation and sought to assess hemodynamic and cardiac responses triggered by SMR before and after a prolonged occlusion of the LAD.Methods. A bypass-line between the ascending aorta and the coronary sinus was made to perform a selective retrograde perfusion of the great cardiac vein with oxygenated blood (SMR). A Control group (n=6) was assigned to collect baseline data, and an SMR group (n=6) was dedicated to undergo SMR with occlusion of LAD for 240 minutes. Cardiac output (CO), maximal pressure in the LV (Pmax in-LV), stroke volume (SV), left ventricular ejection fraction (LVEF), diastolic durations, heart rate, and arterial systemic pressure were evaluated with conductance catheters for the following periods: basal (before SMR), SMR with patent LAD, and SMR with occluded LAD. In order to assess peripheral perfusion, patterns of sublingual microcirculation were analyzed. At the end of the procedures, the hearts were harvested for histology. Results. Echographic LVEF evaluation was affected by sternotomy, but conductance catheter evaluation was not. Following pericardiotomy, CO decreased by 7.51% (P < 0.05). SMR with patent LAD showed inotropic properties with improvements in CO, SV, Pmax in-LV and LVEF (P < 0.0001). Following LAD occlusion, SMR supplied myocardial oxygenation with hemodynamic compensation and preserved the peripheral perfusion. Histology confirmed no signs of infarct. Conclusions. SMR showed capacities to produce inotropic effects and protect against ischemia, opening interesting potential applications