The mitral valve in the heart sometimes struggles with diseases and complications, and needs to be replaced. This problem becomes more frequent with the ageing of the population in developed countries. The most common practice consists of suturing a prosthetic valve into place. However, newer methods are being devised and tested to make the surgery faster and less invasive. In particular, various types of new sutureless heart valve systems exist on the market. However, there is still a need for a tool designed for the intracardiac delivery and anchoring of a prosthetic mitral valve, as addressed here. A number of criteria and specifications were set by researchers at the Robarts Research Institute (London, ON) who came up with the design task. To address their request, ten conceptual designs of a sutureless, virtual-reality guided, self-anchoring, intracardiac system were developed to hold a prosthetic mitral valve, deliver it safely, and quickly affix it in position. The winning concept adequately met the design criteria. Two prototypes were manufactured. The attachment of a prosthetic valve to a simulated mitral valve annulus was tested with the first prototype to verify feasibility and measure leakage. The second prototype was pressure tested in a dynamic surgical phantom reproducing the circulatory conditions during surgery. While the preliminary feasibility of the concept was established, recommendations were made to develop a less bulky design.

The objective of this thesis is to examine the possibility to determine the mechanical heart rate using intracardiac impedance in the time domain. Deducing the mechanical heartrate from the impedance could help improve the performance of implanted devices that today depend on the measurement of the heart’s electrical activity. Cardiogenic – also known as intracardiac – impedance is based on the difference in conductivity between heart muscle tissue and blood, making the impedance vary as the heart is filled and emptied. The data used in this thesis was acquired from three previous studies performed by St Jude Medical, two clinical and one preclinical. Two impedance measurement configurations were chosen from these studies, one bipolar and one quadropolar. To deduce the heart rate from the intracardiac impedance six algorithms were evaluated. Three using continuous peak detection and three evaluating small frames of the impedance signal.The peak detection algorithms were peak detection on the impedance signal itself, on its derivative  and on its integral. The three others were an Auto Correlation Function (ACF), an Average Magnutide Difference Function (AMDF) and an Average Wave Comparison Function (AWCF). In order to assess the heart rates deduced from the intracardiac impedance by the algorithms, these rates were compared to both the IEGM or the ECG (depending on which study was at hand) and the blood pressure. Several issues affected the performance of the algorithms. Impedance morphology can vary between patients. Some display so called “double peaks”, making it hard to decide whether a patient has for example a pulse of 80 bpm or of 160 bpm. The impedance morphology was also affected by amplitude modulation with the respiration frequency which in some patients cause difficulties to analyze the impedance signal. The results show that the two impedance measurement configurations perform equally well and that the ACF method was the overall best performing algorithm. They also show that individual patient impedance morphology has a large influence on the results and for future studies it should therefore be interesting to calibrate the algorithms for each patient, as this should improve performance.

The mitral valve in the heart sometimes struggles with diseases and complications, and needs to be replaced. This problem becomes more frequent with the ageing of the population in developed countries. The most common practice consists of suturing a prosthetic valve into place. However, newer methods are being devised and tested to make the surgery faster and less invasive. In particular, various types of new sutureless heart valve systems exist on the market. However, there is still a need for a tool designed for the intracardiac delivery and anchoring of a prosthetic mitral valve, as addressed here. A number of criteria and specifications were set by researchers at the Robarts Research Institute (London, ON) who came up with the design task. To address their request, ten conceptual designs of a sutureless, virtual-reality guided, self-anchoring, intracardiac system were developed to hold a prosthetic mitral valve, deliver it safely, and quickly affix it in position. The winning concept adequately met the design criteria. Two prototypes were manufactured. The attachment of a prosthetic valve to a simulated mitral valve annulus was tested with the first prototype to verify feasibility and measure leakage. The second prototype was pressure tested in a dynamic surgical phantom reproducing the circulatory conditions during surgery. While the preliminary feasibility of the concept was established, recommendations were made to develop a less bulky design.

The mitral valve in the heart sometimes struggles with diseases and complications, and needs to be replaced. This problem becomes more frequent with the ageing of the population in developed countries. The most common practice consists of suturing a prosthetic valve into place. However, newer methods are being devised and tested to make the surgery faster and less invasive. In particular, various types of new sutureless heart valve systems exist on the market. However, there is still a need for a tool designed for the intracardiac delivery and anchoring of a prosthetic mitral valve, as addressed here. A number of criteria and specifications were set by researchers at the Robarts Research Institute (London, ON) who came up with the design task. To address their request, ten conceptual designs of a sutureless, virtual-reality guided, self-anchoring, intracardiac system were developed to hold a prosthetic mitral valve, deliver it safely, and quickly affix it in position. The winning concept adequately met the design criteria. Two prototypes were manufactured. The attachment of a prosthetic valve to a simulated mitral valve annulus was tested with the first prototype to verify feasibility and measure leakage. The second prototype was pressure tested in a dynamic surgical phantom reproducing the circulatory conditions during surgery. While the preliminary feasibility of the concept was established, recommendations were made to develop a less bulky design.

Effects of substance P (SP) and selective tachykinin agonists on neurotransmission at guinea-pig intracardiac ganglia were studied in vitro. Voltage responses of neurons to superfused tachykinins and nerve stimulation were measured using intracellular microelectrodes. Predominant effects of SP (1 μM) were to cause slow depolarization and enable synaptic transmission at low intensities of nerve stimulation. Augmented response to nerve stimulation occurred with 29 of 40 intracardiac neurons (approx. 73%). SP inhibited synaptic transmission at 23% of intracardiac neurons but also caused slow depolarization. Activation of NK3 receptors with 100 nM [MePhe 7]neurokinin B caused slow depolarization, enhanced the response of many intracardiac neurons to low intensity nerve stimulation or local application of acetylcholine, and triggered action potentials independent of other stimuli in 6 of 42 neurons. The NK1 agonist [Sar 9,Met(O2)11]SP had similar actions but was less effective and did not trigger action potentials independently. Neither selective agonist inhibited cholinergic neurotransmission. We conclude that SP can function as a positive or negative neuromodulator at intracardiac ganglion cells, which could be either efferent neurons or interneurons. Potentiation occurs primarily through NK3 receptors and may enable neuronal responses with less preganglionic nerve activity. Inhibition of neurotransmission by SP is most likely explained by the known blocking action of this peptide at ganglionic nicotine receptors.

The objective of the study was to determine if chronic interruption of all extrinsic nerve inputs to the heart alters cholinergic-mediated responses within the intrinsic cardiac nervous system (ICN). Extracardiac nerve inputs to the ICN were surgically interrupted (ICN decentralized). Three weeks later, the intrinsic cardiac right atrial ganglionated plexus (RAGP) was removed and intrinsic cardiac neuronal responses were evaluated electrophysiologically. Cholinergic receptor abundance was evaluated using autoradiography. In sham controls and chronic decentralized ICN ganglia, neuronal postsynaptic responses were mediated by acetylcholine, acting at nicotinic and muscarinic receptors. Muscarine- but not nicotine-mediated synaptic responses that were enhanced after chronic ICN decentralization. After chronic decentralization, muscarine facilitation of orthodromic neuronal activation increased. Receptor autoradiography demonstrated that nicotinic and muscarinic receptor density associated with the RAGP was unaffected by decentralization and that muscarinic receptors were tenfold more abundant than nicotinic receptors in the right atrial ganglia in each group. After chronic decentralization of the ICN, intrinsic cardiac neurons remain viable and responsive to cholinergic synaptic inputs. Enhanced muscarinic responsiveness of intrinsic cardiac neurons occurs without changes in receptor abundance.

<p>Implemented on an intracardiac echocardiography transducer, acoustic radiation force methods may provide a useful means of characterizing the heart's elastic properties. Elasticity imaging may be of benefit for diagnosis and characterization of infarction and heart failure, as well as for guidance of ablation therapy for the treatment of arrhythmias. This thesis tests the hypothesis that with appropriately designed imaging sequences, intracardiac acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) are viable tools for quantification of myocardial elasticity, both temporally and spatially. Multiple track location SWEI (MTL-SWEI) is used to show that, in healthy in vivo porcine ventricles, shear wave speeds follow the elasticity changes with contraction and relaxation of the myocardium, varying between 0.9 and 2.2 m/s in diastole and 2.6 and 5.1 m/s in systole. Infarcted tissue is less contractile following infarction, though not unilaterally stiffer. Single-track-location SWEI (STL-SWEI) is proven to provide suppression of speckle noise and enable improved resolution of structures smaller than 2 mm in diameter compared to ARFI and MTL-SWEI. Contrast to noise ratio and lateral edge resolution are shown to vary with selection of time step for ARFI and arrival time regression filter size for STL-SWEI and MTL-SWEI. </p><p>In 1.5 mm targets, STL-SWEI achieves alternately the tightest resolution (0.3 mm at CNR = 3.5 for a 0.17 mm filter) and highest CNR (8.5 with edge width = 0.7 mm for a 0.66 mm filter) of the modalities, followed by ARFI and then MTL-SWEI.</p><p>In larger, 6 mm targets, the CNR-resolution tradeoff curves for ARFI and STL-SWEI overlap for ARFI time steps up to 0.5 ms and kernels $\leq$1 mm for STL-SWEI. STL-SWEI can operate either with a 25 dB improvement over MTL-SWEI in CNR at the same resolution, or with edge widths 5$\times$ as narrow at equivalent CNR values, depending on the selection of regression filter size. Ex vivo ablations are used to demonstrate that ARFI, STL-SWEI and MTL-SWEI each resolve ablation lesions between 0.5 and 1 cm in diameter and gaps between lesions smaller than 5 mm in 3-D scans. Differences in contrast, noise, and resolution between the modalities are discussed. All three modalities are also shown to resolve ``x''-shaped ablations up to 22 mm in depth with good visual fidelity and correspondence to surface photographs, with STL-SWEI providing the highest quality images. Series of each type of image, registered using 3-D data from an electroanatomical mapping system, are used to build volumes that show ablations in in vivo canine atria. In vivo images are shown to be subject to increased noise due to tissue and transducer motion, and the challenges facing the proposed system are discussed. Ultimately, intracardiac acoustic radiation force methods are demonstrated to be promising tools for characterizing dynamic myocardial elasticity and imaging radiofrequency ablation lesions.</p> / Dissertation

Autonomic control of cardiac function depends on the coordinated activity generated by neurons within the intracardiac ganglia, and intrinsic feedback loops within the ganglia provide precise control of cardiac function. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are important regulators of cell-to-cell signaling within the intracardiac ganglia, and PACAP and VIP action on these ganglia, mediated through associated receptors, play an important role in the regulation of coronary blood flow, cardiac contraction, relaxation, and heart rate. Results reported here using PACAP and VIP provide direct evidence of some of the complex signaling which occurs in neurons of the rat intracardiac ganglia.

Intrinsic neural plexus of the mouse heart has not been adequately investigated despite the extensive use of this species in experimental cardiology. Both the normal and the genetically modified mice are excellent models for investigations of molecular mechanisms of cardiac arrhythmia associated with disbalance between sympathetic and parasympathetic neural inputs to the heart. The purpose of this study was to determine the topographical and structural organization of the mouse cardiac neural plexus, also to determine the distribution of cholinergic (parasyphatetic), adrenergic (symphatetic), and sensory (peptidergic) neural components in whole-mount mouse heart preparations using double immunohistochemical labeling. Results showed, that despite substantial anatomic differences in the number and distribution of epicardiac ganglia, structural organization of intrinsic ganglionated plexus in the mouse heart corresponds in general to that of other mammalian species, including the human. Majority of nerves and neural bundles in the mouse heart are mixed, but a lot of them express either adrenergic or cholinergic phenotype. Therefore, the selective stimulation and/or ablation of the functionally distinct intrinsic neural pathways appears fairly available in the mouse heart model and this should allow further investigations on specific effects of distinct intrinsic nerves and ganglia on cardiac function. / Intrakardinė nervų sistema atlieka svarbų vaidmenį reguliuodama širdies ritmą, miokardo laidumą ir susitraukimo jėgą bei vainikinių arterijų tonusą. Tyrinėjant simpatinės-parasimpatinės nervų sistemos tonusų disbalansą, širdies ritmo sutrikimų bei miokardo išemijos molekulinius mechanizmus, pastaruoju metu eksperimentiniais modeliais yra pasirenkamos įvairios genetiškai modifikuotų laboratorinių pelių linijos, tačiau pelės širdies vidusieninis nervinis rezginys iki šiol nebuvo dažnas neuroanatominių tyrimų objektas. Šiame darbe buvo ištirtos pelės širdies nervinio rezginio topografinės bei struktūrinės ypatybės totaliuose (nesupjaustytuose ir nesukarpytuose) širdies preparatuose, panaudojant histocheminį acetilcholinesterazės metodą, taip pat imunohistochemiškai ištirtos pelės širdies adrenerginės (simpatinės), cholinerginės (parasimpatinės) bei peptiderginės (sensorinės) nervinės struktūros. Rezultatai rodo, kad nežiūrint individualaus epikardinio rezginio variabilumo rūšies viduje, suaugusios pelės ir žmogaus intrakardinė nervinė sistema yra daug kuo panaši. Pelės širdyje yra cholinerginių, adrenerginių ir peptiderginių nervinių skaidulų. Dauguma pelės intrakardinių nervų ir nervinių pluoštų yra mišrūs, tačiau yra nervų, kuriuose yra tik cholinerginiai arba tik adrenerginiai aksonai. Šio neuroanatominio darbo rezultatai sudaro realias prielaidas tobulinti esamus ir kurti naujus širdies ritmo sutrikimų mechanizmų bei jų gydymo fiziologinių eksperimentų modelius, kurių dėka... [toliau žr. visą tekstą]

La fibrilación auricular es la arritmia más frecuente en la práctica clínica, con una prevalencia que alcanza el 10% en la población mayor de 70 años, y unas perspectivas de incremento en consonancia con el aumento de la esperanza de vida. No obstante, a pesar de ser la arritmia más frecuente, los mecanismos causantes de su generación y persistencia no se conocen con exactitud. Por esta razón, los estudios cuyo objetivo sea profundizar en los mecanismos que envuelven la citada arritmia son de gran ayuda para el desarrollo de protocolos clínicos que mejoren el diagnóstico, y permitan seleccionar los tratamientos más apropiados. Numerosos estudios científicos han indagado en cuáles son los factores que afectan al estado electrofisiológico de las aurículas, responsables de la iniciación y mantenimiento de la fibrilación, así como en los que gobiernan la transmisión de los impulsos eléctricos entre la aurícula y el ventrículo, donde el sistema nervioso autónomo se ha apuntado como uno de los factores responsables. En esta tesis doctoral se ha estudiado el efecto sobre la actividad auricular y ventricular, del anestésico más comúnmente usado en terapias destinadas a restablecer el ritmo sinusal en pacientes con episodios de fibrilación auricular. Este anestésico es el propofol (2,6-diisopropylphenol), que es un rápido anestésico intravenoso. La rápida redistribución y metabolismo del propofol resultan en una rápida eliminación de aproximadamente 1 hora, haciéndolo útil para sedaciones de corta duración. La hipótesis de este estudio es si el propofol puede alterar la actividad auricular durante la fibrilación auricular. Simultáneamente a la realización de los procedimientos de ablación, se realizan registros electrocardiográficos y electrogramas auriculares. Los electrogramas permiten extraer información local de las aurículas, muy útil para reflejar los procesos electrofisiológicos que ocurren durante la fibrilación auricular. Habitualmente, los registros internos de epi / Cervigón Abad, R. (2009). Signal processing of intracardiac recordings for the evaluation of propofol effects during atrial fibrillation [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/5766 / Palancia