The isolated normothermic hemoperfused working porcine heart

Deckblatt-Impressum persönlicher Dank Inhaltsverzeichnis Abkürzungsverzeichnis Einleitung Zielsetzung Literaturübersicht Material und Methoden Ergebnisse Diskussion Zusammenfassung Summary Ausblick Probleme der Doktorarbeit Literaturverzeichnis Tabellen- und Abbildungsverzeichnis wissenschaftliche Publikationen Selbständigkeitserklärung DanksagungZiel dieser Studie war es, die Methode eines isolierten und normothermen hämoperfundierten arbeitenden Schweineherzens zu etablieren und zu charakterisieren. Die hämodynamischen und klinisch chemischen Parameter wurden über einen Zeitraum von sieben Stunden ermittelt. Es erfolgte eine akute Ischämiephase (2 Std.) mit nachfolgender Reperfusionphase (4 Std.). Darüber hinaus wurde der perivaskuläre und interstitielle Kollagengehalt mittels Elektronen-mikroskopie, Western Blot und Sirius-Rot-Färbung untersucht. Nachdem die Herzen prä-pariert waren, wurden sie an eine speziell entwickelte Hämoperfusionsapparatur angeschlossen. Nach 1-stündiger Perfusion (Adaptationsphase) wurden die Herzen in fünf Versuchsgruppen eingeteilt: 1\. working heart -Herzen (WH) 2\. Infarkt-Herzen (MI) 3\. mit Angiotensin I behandelte Herzen (Ang I-MI) 4\. mit Quinaprilat und Angiotensin behandelte Herzen (Q-Ang I-MI) 5\. mit Quinaprilat behandelte Herzen (Q-MI) Blutgasanalysen und Oxymetrie wurden zu Beginn der Versuche und alle 30 min während des Versuches abgenommen. Der koronare Perfusionsfluss und -druck, die Herzfrequenz, der linksventrikuläre systolische und enddiastolische Druck wurden über einen angeschlossenen Computer online gemessen. Bei allen Versuchsgruppen bleiben pH, pO2, pCO2, Bikarbonat, Kalium, Kalzium, Natrium, Glucose und Laktat im arteriellen und venösen Blut sowie im Dialysat im physiologischen Bereich. Kalium zeigt zum Ende der Versuche einen signifikanten Anstieg, liegt damit aber noch im Referenzbereich. Die Herzfrequenz, LVEDP und der Perfusionsdruck steigen bei den infarzierten Herzen signifikant an (P<0.05). Der Gesamt-Kollagengehalt steigt im infarzierten Myokardgewebe in der frühen Phase der Reperfusion an. Findet eine frühzeitige Behandlung mit Quinaprilat statt, kann der Anstieg von Kollagen Typ III abgeschwächt werden. Abschließend kann man sagen, dass wir ein isoliertes normothermes hämoperfundiertes arbeitendes Ischämie- Reperfusionsmodell des Schweineherzens entwickelt und charakterisiert haben. Unsere Ergebnisse zeigen, dass anhand dieses ex vivo-Modells frühe physiologische und morphologische Effekte des Herzinfarktes untersucht werden können. Gleichfalls haben wir eine neue Möglichkeit geschaffen, um pharmakologische Interventionen zu untersuchen, welche einer Schädigung des Herzens und dem pathologischen kardialen Remodeling nach Myokardinfarkt vorbeugen können.The principal aim of this study was to establish and characterize the model of an isolated normothermic, hemoperfused working porcine heart. Hemodynamic and clinical chemical parameters were investigated for a period of seven hours. Moreover, we induced acute ischemia (2h), followed by reperfusion (4h) to investigate perivascular and interstitial collagen content using electron microscopy, western blot analysis and sirius red staining. The hearts were prepared and connected to a special perfusion system. After 1 hour of perfusion (adaptation time) the hearts were randomized to several groups: 1\. working hearts (control), 2\. infarcted hearts (MI; R. circumflexus), 3\. infarcted hearts treated with Angiotensin I (Ang I-MI), 4\. infarcted hearts treated with Ang I and Quinaprilat (Q-Ang I-MI) and 5\. infarcted hearts treated with Quinaprilat (Q-MI) Blood gas and oxymetric analysis were checked at the beginning of the experiment and all 30 min. Coronary perfusion, perfusion pressure, right ventricular pressure, heart rate, left ventricular systolic and end-diastolic pressure were measured online using a personal computer. In all groups and all media pH, pO2, pCO2, bicarbonate, glucose, natrium, calcium and lactate remained within the normal range. Potassium significantly increased at the end of the experiment but remained within the normal range. Heart rate, LVEDP and perfusion pressure of infarcted hearts elevated significantly (P<0.005). In the infarct area total collagen content was early increased after ischemia-reperfusion. Early application of Quinaprilat attenuated collagen type III accumulation. Conclusion: We have established and characterized a new isolated porcine ischemia reperfusion model. Our data indicate that the early physiological and morphological effects of a myocardial infarction can be investigated ex vivo. In parallel, we have the possibility to perform new pharmacological strategies to prevent heart failure and pathologic cardiac remodeling post-MI

DOES THE METABOLIC COST OF LOAD CARRIAGE DIFFER BETWEEN MALES AND FEMALES?

DOES THE METABOLIC COST OF LOAD CARRIAGE DIFFER BETWEEN MALES AND FEMALES? Habighorst HE, Baker RL, Berglund KM, Gutierrez SA, Dierman AR, Christman EE Department of Health and Human Performance PURPOSE: The scientific understanding of energy use during load carriage suggests that the additional metabolic increment necessary to support an external load is determined by the load’s percentage of the subject’s body weight. Accordingly, for comparison purposes experimental undertakings often adjust the mass of an external load to represent a constant fraction of each subject’s mass. However, in occupational and applied settings, individuals are frequently asked to support similar absolute loads irrespective of their body weight. Here, we evaluated whether the energy requirements in male and female subjects differed during treadmill walking across a range of speeds, while supporting a common 20.5kg external load. METHODS: We measured VO2 during three, 5min trials, administered with a 20.5kg pack, on a level treadmill at 1.7, 1.8, 1.9 ms-1, from 20 subjects(age = 22.1±2.4yrs), who had been assigned as sex-matched pairs on the basis of mass (10 males, Mb = 72.6±6.3kg; 10 females, Mb = 72.8±6.2kg; difference between pairs = 0.6±0.5kg, max 1.4kg). RESULTS: Measured values of VO2 in females were 24.7±4.2, 28.9±3.7, and 30.8±3.3ml kg-1 min-1 at 1.7, 1.8, and 1.9 m s-1, respectively, these values in males, although lower, were indistinguishable (min p-value=0.08) and were 23.1±3.3, 25.8±3.7, and 30.1±4.6 ml kg-1 min-1 at the same speeds. Nonetheless, our data provide 27 points of comparison, with identical loads, at similar speeds (3 of 10 female subjects were unable to complete the 1.9 ms-1 trial); in 8 of these 27 points of comparison females were more economical than their matched pair. CONCLUSION: Our data lend support to the presence of a sex based difference in load carriage economy, warranting further study. We note also that the similar rates of energy expenditure between the sexes observed here, translate to higher relative intensities for females due to their likely lower mass-specific aerobic capacities (i.e. VO2max)

A global review of marine air pollution policies, their scope and effectiveness

Shipping is associated with various environmental impacts, such as pollutants discharged to air and sea. Much of this pollution appears to be unregulated, and global emissions from shipping are expected to more than triple between 2020 and 2050. This paper reviews global, national, regional and port-level legislative approaches that have been implemented to reduce emissions of carbon dioxide (CO2), nitrous oxides (NOx), sulphur oxides (SOx) and particulate matter (PM). Policies are identified on the basis of a systematic review of the literature in combination with a detailed analysis of the respective global, national and local policy initiatives. Findings suggest that many policies are voluntary or, in ports, incentive-based; regulatory approaches are largely limited to Emission Control Areas. Policies also focus on efficiencies, they are not concerned with absolute pollutant and greenhouse gas levels. No policies incentivizing or forcing the transition to zero-carbon fuels were identified. As ports can define limits to pollution, for instance by demanding shore power use, they can significantly affect the clean development of the sector. Further legislation will be needed nationally to counterbalance the lack of supranational ambition on pollutants and climate change mitigation

Seismic and field evidence for selective inversion of Cretaceous normal faults, Salta rift, northwest Argentina

Northwestern Argentina was the site of the continental Salta rift in Cretaceous to Paleogene time. The Salta rift had a complex geometry with several subbasins of different trends and subsidence patterns surrounding a central high. Fault trends in the rift were extremely variable. There is evidence of normal and/or transfer faults trending N, NE, E and SE. It is not clear if all these faults were active at the same time, indicating a poorly defined extension direction, or if they formed in different, non-coaxial extension phases. In either case, their trends were very likely influenced by preexisting fault systems. Beginning in early Eocene time, the rift basins were superseded by Andean foreland basins and later became caught in the Andean thrust deformation propagating eastward, resulting in the inversion of rift faults. Due to their different orientations, not all faults were equally prone to reactivation as thrusts. N to NNE trending faults were apparently most strongly inverted, probably often to a degree where the traces of their normal fault origin have become obliterated. We present seismic evidence of moderately inverted N trending faults in the Tres Cruces basin and field examples of preserved E trending normal faults. However, reactivation sometimes also affects faults trending approximately parallel to the main Neogene shortening direction, indicating short-term deviations from the general pattern of Neogene thrust deformation. These pulses of orogen-parallel contraction may be linked to the intermittent activity of oblique transfer zones.Fil: Kley, Jonas. Universitat Jena; AlemaniaFil: Rossello, Eduardo Antonio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Geología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monaldi, Cesar Ruben. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Habighorst, Bjórn. Universität Karlsruhe; Alemani

DOES THE METABOLIC COST OF LOAD CARRIAGE DIFFER BETWEEN MALES AND FEMALES?

R.L. Baker, K.M. Berglund, H.E. Habighorst, J.T. Strang, C.J. Alfiero, M.W. Bundle University of Montana, Missoula, MT PURPOSE: The scientific understanding of energy use during load carriage suggests that the additional metabolic increment necessary to support an external load is determined by the load’s percentage of the subject’s body weight. Accordingly, for comparison purposes experimental undertakings often adjust the mass of an external load to represent a constant fraction of each subject’s mass. However, in occupational and applied settings, individuals are frequently asked to support similar absolute loads irrespective of their body weight. Here, we evaluated whether the energy requirements in male and female subjects differed during treadmill walking across a range of speeds, while supporting a common 20.5kg external load. METHODS: We measured VO2during three, 5min trials, administered with a 20.5kg pack, on a level treadmill at 1.7, 1.8, 1.9 m s-1, from 20 young adults(age = 22.1±2.4 yrs),who had been assigned as sex-matched pairs on the basis of mass (10 males, Mb= 72.6±6.3kg; 10 females, Mb = 72.8±6.2kg; range 63.6-82.7kg, difference between pairs = 0.6±0.5kg, max 1.4kg). RESULTS: Measured values of VO2in females were 24.7±4.2, 28.9±3.7, and 30.8±3.3ml kg-1 min-1at 1.7, 1.8, and 1.9 m s-1, respectively, whereas these values in males, although lower, were statistically(min p-value = 0.08) indistinguishable and were 23.1±3.3, 25.8±3.7, and 30.1±4.6 ml kg-1 min-1at the same speeds. Nonetheless, we note our data provide 27 points of comparison, with identical loads, at similar speeds (3 of 10 female subjects were unable to complete the 1.9 m s-1trial), across 10 males and females who are very similar in mass; in 8 of these 27 points of comparison females were more economical than their matched pair. CONCLUSION: Our data lends support to the presence of a sex based difference in load carriage economy, warranting further study. We note also that the similar rates of energy expenditure between the sexes observed here, translate to higher relative intensities for females due to their likely lower mass-specific aerobic capacities (i.e. VO2max). This work was supported by a multi-investigator award, US Forest Service Agreement # 16-CR-11138200-005, to MB and colleagues