No description available.

Our purpose was to identify and localize intrinsic cardiac ganglia innervating distinct regions of the heart using postmortem tracing of nerve projections with DiI, a method not previously used to study the intrinsic cardiac nervous system. We also investigated the possibility of collateral innervation of myocardium and intrinsic ganglia. In isolated paraformaldehyde-fixed guinea pig hearts, crystals of DiI (1,1′- dioctadecyl-3,3,3′,3′-tetramethylin-docarbocyanine perchlorate) were inserted into the posterior ventricular myocardium below the atrioventricular groove, the right atrium, or the left ventricular septum. Hearts were placed in the dark at 37°C for 2-14 weeks to allow DiI diffusion within neuronal membranes. Labeled neurons were observed in intracardiac ganglia after at least 4 weeks of dye exposure. Labeling was restricted to the inferior-most ganglia (those near the atrioventricular groove) when DiI was inserted into the posterior ventricular myocardium and to ganglia near the sinus node after right atrial DiI placement. Application of DiI to the left ventricular septum resulted in neuron labeling in ganglia primarily in the interatrial septum near the atrioventricular node. After 8 weeks, DiI-labeled nerve fibers and varicosities were seen surrounding unlabeled neurons in some ganglia, suggesting that axons terminating in or passing through the DiI application site in posterior ventricular tissue had collateral branches innervating these ganglia. These results indicate that intrinsic innervation of major cardiac subdivisions is accomplished by regionally segregated cardiac ganglia. Also, tracing with DiI has provided evidence for collateral nerve projections that could be the substrate for novel intracardiac regulatory circuits.

Stress hormones, adrenaline and noradrenaline, have been shown to be critical for heart development. Mice lacking dopamine greek lower case letter beta]-hydroxylase (Dbh), an enzyme responsible for synthesis of these adrenergic hormones, die during mid-gestation due to cardiac failure. Prior research showed that adrenergic cells are found within the electrical conduction system of the heart, and adrenergic deficiency leads to slowed cardiac conduction during embryogenesis. Microarray analysis of wild-type (Dbh+/+) and knockout (Dbh-/-) mouse hearts revealed significant differences in expression of retinoic acid (RA) signaling genes. RA signaling has also been shown to be critical for heart development. These data suggest that heart failure due to adrenergic deficiency may be dependent upon RA signaling. This led to the hypothesis that adrenergic hormones promote the development of the electrical conduction system through modulation of RA signaling. To test this, embryonic mouse hearts were cultured with LE 135, a RA receptor blocker. Heart rate, arrhythmic index (AI) and conduction time were measured. Under these conditions there was a marked increase in arrhythmias. Hearts treated with LE 135 showed a mean AI of 0.232±0.057 after 24 hours of treatment while when untreated had an AI of 0.083±0.028 (p<0.05;n=15). In contrast, there was no significant change in heart rate or conduction speed after 24 hours with or without the retinoic acid receptor blocker. To determine if adrenergic stimulus influences retinoic acid response, an established RA-sensitive reporter cell line was employed. These F9-RARE-LacZ cells were treated with forskolin (cAMP regulator) and isoproterenol (greek lower case letter beta]-agonist) to measure changes in RA signaling. Evaluation of RA signaling showed an increase in retinoic acid responsiveness when treated with an adrenergic signaling agonist.; These results suggest that proper retinoic acid signaling is essential for maintaining cardiac rhythmicity during embryonic development and adrenergic stimulation can influence this response.

Clostridium difficile ist einer der führenden Nosokomialkeime in Bezug auf postoperative Diarrhoe. Die Inzidenz ist steigend und der Verlauf bei fulminanter Infektion häufig fatal. Es besteht der Anspruch der Vermeidung schwerer Verläufe und der horizontalen Verbreitung des Erregers. Ziel der Arbeit war, für den prä-, intra- und postoperativen Zeitraum Risikofaktoren zu identifizieren, welche Einfluss auf Ausprägung und Schwere der Infektion hatten. Die vorliegende klinische Studie umfasst 2.823 Patienten mit Diarrhoe nach kardiochirurgischem Eingriff, darunter 1.256 Patienten mit Clostridium-difficile-Nachweis, welche im Herzzentrum Leipzig von April 1999 bis April 2011 operativ versorgt worden sind. Die Datenanalyse erfolgte retrospektiv an zuvor festgelegten Parametern, die mittels statistischer Verfahren analysiert wurden. Besonderes Augenmerk wurde auf die Entwicklung gastrointestinaler Komplikationen und die Mortalität gelegt. Risikofaktoren für eine fulminante CDI waren u.a. männliches Geschlecht, kardiopulmonale Komorbiditäten, Diabetes mellitus Typ II, Verwendung von Assist-Systemen, perioperative Transfusionstherapie, sowie lange Operationszeiten und ein verlängerter Aufenthalt auf Intensivstation. Das Überleben bei fulminanter Infektion war mit einer Sterblichkeit von 63,4% bei einer 30-Tages-Mortalität von 21,6% deutlich schlechter als das der Vergleichsgruppen. Die Identifikation der perioperativen Risikofaktoren soll eine individualisierte Stratifizierung und damit die optimale Überwachung von Hochrisikopatienten für einen frühen Therapiebeginn und im besten Falle eine Prävention möglich machen.

Contexte : Les maladies cardiovasculaires dont l'angine et l'infarctus sont un fléau grandissant pour les Canadiens. En 2008, les femmes canadiennes sont 16% plus susceptibles de succomber à un infarctus que les hommes. Pour améliorer la qualité de vie des patients souffrant d'angine ou d'infarctus, la perfusion transluminale per cutanée (PTCA) s'avère le traitement de choix. Suite à celle-ci, il est recommandé d'effectuer des modifications d'habitudes de vie. Cependant, les femmes cardiaques devant modifier leurs habitudes de vie ont une perception de la maladie différente des hommes mais les caractéristiques présentes lors de changement d'habitude de vie ne sont pas connues. Le nouveau contexte de la PTCA n'est pas adapté à cette population grandissante. Objectif: Décrire les caractéristiques présentes lors d'un changement dans le processus de modification de comportements à risque des femmes ayant subi une PTCA. Méthodologie : Cette étude descriptive. L'échantillon non probabiliste de convenance est composé de 22 femmes (X= 65.4 ans) ayant subi une PTCA au CHUS-Fleurimont. Toutes les participantes complétaient le même questionnaire à 1- 2 semaines (Tl) et à 4 mois post-PTCA (T2) lors d'une rencontre à leur domicile. Les questions évaluaient les trois habitudes de vie en lien avec l'alimentation, l'activité physique et le tabagisme ainsi que les principales caractéristiques pouvant être présentes lors d'une modification de comportement à risque (soutien des proches, perception de la maladie, fatigue, dépression, stress, optimisme, variables sociodémographiques, facilitants et barrières perçues par les participantes). Des statistiques descriptives ont été réalisées. Des tests non paramétriques (a = 0.05) ont été faits pour comparer les participantes entre le Tl et le T2 (Wilcoxon) puis des sous-groupes de celles-ci en fonction de leur motivation à modifier leurs comportements à risque à T2 (Mann-Withney et Krustall-Wallis). Les données qualitatives ont été regroupées par catégorie à l'aide d'une analyse de contenu. Résultats : Les femmes de l'étude identifient plus de symptômes de la maladie, sont plus fatiguées (p=0.01) et plus stressées (p=0.04) au Tl (p=0.000) qu'au T2. Celles-ci perçoivent leur maladie cardiaque comme chronique (p=0.006) et ont une meilleure compréhension de celle-ci (p=0.007) 4 mois suivant la PTCA. Le soutien des professionnels de la santé ainsi que les programmes de réadaptation cardiaque sont perçus comme des facilitants à la modification de comportement au même titre que celui de la famille et des amis. Les symptômes physiques (douleurs aux jambes, au dos, etc.) et les symptômes dépressifs sont identifiés comme des barrières à la modification de comportement. Conclusion : Cette étude a permis de faire ressortir certaines caractéristiques présentes tant en post-PTCA que lors d'un changement dans le processus de modification de comportement. D'autres études doivent cependant être conduite afin de valider ces caractéristiques auprès d'un plus grand échantillon et ainsi pouvoir proposer des interventions infirmières d'enseignements solides et structurés à partir de solides assises sur les caractéristiques associées aux femmes ayant subi une PTCA.

No description available.

Aims The aim of this thesis was to describe out-of-hospital cardiac arrest (OHCA) due to drowning from the following angles. In Paper I: To describe the characteristics of OHCA due to drowning and evaluate factors of importance for survival. In Paper II: To describe lifesaving skills and CPR competence among surf lifeguards. In Paper III: To describe the characteristics of interventions performed by the Swedish fire and rescue services (SFARS) and evaluate survival with or without rescue diving units. In Paper IV: To describe the prevalence of possible confounders for death due to drowning. In Paper V: To describe changes in characteristics and survival over time and again to evaluate factors of importance for survival Methods Papers I and III-V are based on retrospective register data from the Swedish OHCA Register reported by Emergency Medical Service (EMS) clinicians between 1990-2011. In addition, in Paper III, the data have been analysed and compared with the SFARS database for rescue characteristics. In Paper IV, the data have been compared with those of the National Board of Forensic Medicine (NBFM). Paper II is a descriptive study of 40 surf lifeguards evaluating delay and CPR quality as peformed on a manikin. Results Survival in OHCA due to drowning is about 10% and does not differ significantly from OHCA with a cardiac aetiology. The proportion of witnessed cases was low. Survival appears to increase with a short EMS response time, i.e. early advanced life support. Surf lifeguards perform CPR with sustained high quality, independent of prior physical strain. In half of about 7,000 drowning calls, there was need for a water rescue by the fire and rescue services. Among the OHCA in which CPR was initiated, a majority were found floating on the surface. Rescue diving took place in a small percentage of all cases. Survival when using rescue divers did not differ significantly from drownings where rescue diving units were not used. No survivors were found after &gt;15 minutes of submersion in warm water. After submersion in cold water, survival with a good neurological outcome was extended. Among 2,166 autopsied cases of drowning, more than half were judged as accidents and about one third as intentional suicide cases. Among accidents, 14% were found to have a cardiac aetiology, while the corresponding figure among suicides was 0%. In a 20-year follow-up of OHCA due to drowning in Sweden, both bystander CPR and early survival to hospital admission are increasing. The proportion of cases alive after one month has not changed significantly during the period. Conclusions Survival from OHCA due to drowning is low. A reduction in the EMS response time appears to have high priority, i.e. early ALS is important. The quality of CPR among surf lifeguards appear to be high and not affected by prior physical strain. In all treated OHCA cases, the majority were found at the surface and survival when rescue diving took place did not appear to be poorer than in non-rescue diving cases. In a minor proportion of cases, cardiac disease could be a confounder for death due to drowning. Bystander CPR in OHCA due to drowning has increased over a 20-year period and the proportion of early survivors to hospital admission is increasing. We speculate that our studies were underpowered with regard to the opportunity adequately to assess the effects of bystander CPR on survival to hospital discharge. A uniform Swedish definition of drowning based on the recommended international terms should be implemented throughout Swedish authorities and health care, in order to enhance the quality of data and improve the potential for future research. / <p>Disputationen sker Fredagen den 20 September 2013, kl. 13.00 Sahlgrens aula, Blå stråket 5, Sahlgrenska universitetssjukhuset, Göteborg.</p>

The aim of this thesis is to replace the intractable problem of using discrete flow models within large vascular networks with a suitably parameterised and tractable continuum perfusion model. Through this work, we directly address the hypothesis that discrete vascular data can be incorporated within continuum perfusion models via spatially-averaged parameterisation techniques. Chapter 1 reviews biological perfusion from both clinical and computational modelling perspectives, with a particular focus on myocardial perfusion. In Chapter 2, a synthetic 3D vascular network was constructed, which was controllable in terms of its size and properties. A multi-compartment static Darcy perfusion model of this discrete system was parameterised via a number of techniques. Permeabilities were derived using: (i) porosity-scaled isotropic (ϕI); (ii) Huyghe and Van Campen (HvC); and (iii) projected-PCA parameterisation methods. It was found that HvC permeabilities and pressure-coupling fields derived from the discrete data produced the best comparison to the spatially-averaged Poiseuille pressure. In Chapter 3, the construction and analysis of high-resolution anatomical arterial vascular models was undertaken. In Chapter 4, various anatomically-derived vascular networks were used to parameterise our perfusion model, including a microCT-derived rat capillary network, a single arterial subtree, and canine and porcine whole-organ arterial models. Allowing for general-connectivity (as opposed to strictly-hierarchical connectivity) yielded a significant improvement on the continuum model pressure. For the whole-organ model however, it was found that the best results were obtained by using porosity-scaled isotropic permeabilities and anatomically-derived pressure-coupling fields. It was also discovered that naturally occurring small length but relatively large radius vessels were not suitable for the HvC method. In Chapter 5, the suitability of derived parameters for use within a dynamic perfusion model was examined. It was found that the parameters derived from the original static network were adequate for application throughout the cardiac cycle. Chapter 6 presents a concluding discussion, highlighting limitations and future directions to be investigated.

Background: Myocardial infarction (MI) results in severe biochemical, physiological, and cellular changes that lead to alterations in the structure and function of the myocardium. Oxidative stress potentiates this remodeling response and is associated with progressive worsening of cardiac function. Accordingly, we used a powerful antioxidant-based therapeutic strategy to improve cardiac health and study redox-dependent signaling. Methods: MI was surgically induced in rats by ligating the left anterior descending coronary artery. Subgroups of MI rats received resveratrol (i.p., 10 mg/kg/day for 28 days beginning immediately post-MI). Cardiac histology and biochemical analyses of genes and proteins implicated in cardiac fibrosis, hypertrophy, and apoptosis, and redox-dependent signaling were analyzed. Results: As expected, MI resulted in profound structural changes to the myocardium. Further, we observed a sharp reduction in nuclear factor-erythroid 2-related factor 2 (Nrf2) and Krüppel-like factor 15 (KLF15), factors that are responsible for maintaining the endogenous antioxidant capacity and regulating cardiac gene expression, respectively. It is likely that disruption of normal KLF15 signaling permitted the expression of several cardiac genes associated with progressive cardiac remodeling. Importantly, daily treatment with resveratrol ameliorated cardiac remodeling, improved redox state, restored Nrf2 expression, and up-regulated KLF15 expression. Further, induction of KLF15 signaling following resveratrol treatment is associated with attenuated expression of several genes implicated in cardiac remodeling. Conclusions: Chronic oxidative stress potentiates cardiac remodeling post-infarct, in part, by suppressing Nrf2 and KLF15 expression. Importantly, we demonstrate that normal KLF15 signaling may be rescued with an antioxidant-based therapy, which may be an attractive therapeutic target to support cardiac health post-MI.

No description available.