An 23 wachen Ratten wurde die dynamische Regulation der Nierengefäße als Antwort auf schwingungsförmige Änderung des renalen Perfusionsdruckes (RPP) gemessen. Es wurden der Renale Perfusionsdruck (RPP), der Nierenarterienfluss (RBF) sowie lokale Gefäßflüsse der Nierenrinde und des äußeren Nierenmark (Laser-Doppler) aufgezeichnet und daraus die entsprechende Conductance (Leitwert) der Gefäße errechnet. Der mittlere RPP wurde rampenförmig mit einer langsamen Änderungsrate gesenkt (dp/dt), wobei nach jeder absteigenden Flanke eine aufsteigende Rampe gleicher Geschwindigkeit gemessen wurde. Eine Überlagerung des RPP mit Schwingungen unterschiedlicher Frequenz (f=0,005, f=0,01 und f=0,02 Hz) bei einer Amplitude von 20 mmHg führte zu einem Anstieg von dp/dt und einem erhöhten Shearstress an der Gefäßwand (WSS). Der Einfluss der Schwingungen auf RCV war signifikant abhängig vom mittleren RPP. So war die Conductance in tieferen Druckbereichen des RPP mehrfach höher als in den Ausgangsdruckwerten. Innerhalb der absteigenden Rampen führte ein Erhöhung der Frequenz zu einem Anstieg der maximalen Amplitude des RVC des Nierengesamtflusses. Die größten Amplituden wurden bei RPP Werten zwischen 58 und 46 mmHg gemessen. Diese Abhängigkeit war bei den ansteigenden Flanken nicht gegeben. Außerdem zeigte sich in den abfallenden Versuchsteilen ein plötzlicher Phasenwechsel zwischen der RPP- und der RVC-Schwingung bei mittleren RPP-Werten zwischen 95 und 80 mmHg. Dies lässt schließen, dass oberhalb dieses Druckwertes aktive myogenen Vasokonstriktion die passiven Gefäßdilatation vollständig ausgleicht, während unterhalb dieses RPP-Wertes die Vasokonstriktion insuffizient reagiert, bis bei ca. 50 mmHg die RCV ausschließlich der passiven Vasodilatation folgt. Höhere Schwingungsfrequenzen führen durch einen Anstieg des WSS zu einer Erhöhung der Amplitude des RVC. Dies bewirkt eine Änderung der charakteristischen renalen Autoregulation des RPP. Auf diese Weise ändert sich die Effizienz der Autoregulation. / In 23 conscious rats, the dynamic features of renal vascular conductance (RVC) in response to oscillatory changes in renal perfusion pressure (RPP) were studied at different mean RPPs. RPP, renal blood flow, and regional cortical and outer-medullary fluxes (laser-Doppler) were continuously recorded and the respective RVCs calculated. Mean RPP was changed ramp-wise with a low rate of change (dp/dt), whereby a decremental ramp was immediately followed by an incremental ramp. Superimposing RPP oscillations (amplitude 20 mmHg) of different frequencies (f=0.005, f=0.01, and f=0.02 Hz) increased maximum dp/dt, and thus increased vascular wall shear stress (WSS). The impact of RPP oscillations on RVC critically depended on mean RPP. RVC oscillations were several times higher at lower mean RPPs than at control RPP During the decremental ramps, increasing the frequency led to an increase in the maximum amplitude of total RVC, and decreased mean RPP where maximum amplitude occurred from 58 to 46 mmHg. This frequency dependence was abolished during incremental ramps. Lowering mean RPP resulted in a sudden reversal of phase between RPP and RVC oscillations at mean RPP between 95 and 80 mmHg. It is concluded that, above this RPP, myogenic vasoconstriction fully counterbalances passive vasodilatation, whereas, below that RPP, myogenic constriction gradually tapers off until, at about 50 mmHg, RVC is exclusively determined by passive dilation. Higher oscillatory frequencies, assumed to be due to increased WSS, elicit a greater response in RVC amplitude as an expression of vessel compliance, and, thus change the RPP characteristics of renal autoregulation. However, the efficiency of autoregulation is thereby barely changed.

Doctor Pharmaceuticae - DPharm / An aqueous extract prepared from the leaves and smaller stems of Leonotis leonurus was used to investigate the potential effects on certain cardiovascular parameters, such as left ventricular systolic pressure, end-diastolic pressure, developed pressure, heart rate, cardiac work and coronary perfusion pressure in isolated rat hearts. Hearts were perfused at constant flow for 3min using the modified Langendorf! perfused model of the heart. Effects of adrenaline and digoxin solutions on the isolated heart were compared to that of the plant extract. Adrenaline produced both positive inotropic and chronotropic effects. Adrenaline increased (p<O.Ol) the left ventricular systolic pressure and hence the left ventricular developed pressure by 40.6% and 43.9% at peak, and 24.3% and 31.9%, after 3min, respectively. Simultaneously, the heart rate and the cardiac work were increased (p<0.01) by 22.5% and 89.4% at peak, and 24.6% and 63%, after 3rnin, respectively. There were no significant effects on the left ventricular diastolic pressure and the coronary perfusion pressure. Digoxin solution (2.5ng/ml) significantly (p<O.Ol) increased the left ventricular systolic pressure by 5.1% after 3min and the left ventricular diastolic pressure by 9.7% at peak and 5.3% after 3min. The heart rate was significantly (p<O.OI) decreased by 3.7% at peak. The cardiac work was increased by 4.5% after 3rnin. Digoxin did not significantly affect the left end diastolic pressure and the coronary perfusion pressure. The extract of Leonons leonurus at O.lmg/ml increased (p<O.OI) the left ventricular systolic pressure and hence the left ventricular diastolic pressure by 9.7% and 10.7% at peak, and 5.4% and 5.5% after 3rnin, respectively. The cardiac work was increased (p<O.Ol) by 10.1% at peak. Leonotis leonurus (0.1mg/ml) did not significantly affect the left ventricular end diastolic pressure, the heart rate and the coronary perfusion pressure. At 0.5mg/ml, the left ventricular systolic pressure and hence the left ventricular diastolic pressure were increased (p<0.01) by 14.8% and 15.4% at peak and 7.4% and 7.8% after 3rnin, respectively with a corresponding decrease (p<O.OI) in the coronary perfusion pressure of 8.5% at peak and 4.4% after 3rnin. The cardiac work was increased (p<O.OI) by 13.6% at peak and 5.2% after 3rnin. The extract at 1.0mg/ml increased (p<O.Ol) the left ventricular systolic pressure and hence the left ventricular diastolic pressure by 25.4% and 29.4% at Peak, and 23.1% and 26.3% after 3rnin, respectively. The heart rate was reduced (p<O.OI) by 34.7% at peak and 28.3% after 3min. The cardiac work and the coronary perfusion pressure were decreased (p<O.OI) by 15.9% and 12.1% at Peak and 3.3% and 11.4% after 3rnin. However, at 2.0mg/ml, the left ventricular systolic pressure and the left ventricular diastolic pressure were increased (p<O.OI) by 14.9% at peak. The left ventricular diastolic pressure was decreased (p<O.OI)by 9.8% over the 3rnin. The heart rate was drastically decreased (p<O.OI) by 42.7% after 3rnin. The cardiac work was reduced (p<O.Ol) by 48.8% over the 3min period. Also, the coronary perfusion pressure was decreased (p<0.01) by 16.9% at peak. Thus, Leonatis leonurus produced both positive inotropic and negative chronotropic effects after 3min perfusion, accompanied by a decreased coronary perfusion pressure. Thus, it appears that the extract seemed to contain certain constituents associated with positive inotropic and negative chronotropic agents as wel! as constituents associated with coronary vasodilation. However, at the higher concentration, it seemed to contain some constituents associated with toxic effects on the isolated heart. Therefore, further studies are needed to isolate the various constituents and examine their possible pharmacological effects on the heart individually before it could be considered safe to recommend this plant for its use in the treatment of cardiovascular disease.

Submitted by JOSIANE SANTOS DE OLIVEIRA (josianeso) on 2019-03-25T11:56:58Z No. of bitstreams: 1 Jeferson Cardoso do Rosario_.pdf: 3523684 bytes, checksum: 6d033c623e7ef74a93692efd6ca37e8e (MD5) / Made available in DSpace on 2019-03-25T11:56:58Z (GMT). No. of bitstreams: 1 Jeferson Cardoso do Rosario_.pdf: 3523684 bytes, checksum: 6d033c623e7ef74a93692efd6ca37e8e (MD5) Previous issue date: 2019-01-18 / Nenhuma / O traumatismo cranioencefálico (TCE) é atualmente a terceira maior causa de óbitos no âmbito mundial. Estudos recentes têm demonstrado que a monitorização de pressão intracraniana (PIC), como forma de cálculo da pressão de perfusão cerebral (PPC) é uma ferramenta importante para avaliação do fluxo sanguíneo cerebral (FSC), provocando sensível redução nas taxas de mortalidade. Além do TCE, outras patologias ou situações neurocirúrgicas tem utilizado a técnica de monitorização de PIC. A monitorização desse parâmetro foi proposta já na década de 50, onde um tubo com fluido em contato com o líquido cefalorraquidiano (LCR) era introduzido no espaço intracraniano e conectado a um transdutor de pressão externo. Com a evolução da indústria microeletrônica e dos sistemas microeletromecânicos, foi possível colocar os transdutores na ponta do cateter, permitindo uma monitorização menos invasiva, com menos riscos de infecções. Os cateteres atuais com micro transdutor na ponta podem ser divididos em três grupo: straingauge, fibra óptica e pneumático. Cada grupo possui suas características, entretanto o primeiro tem se demonstrado como solução mais robusta e confiável, com boa relação custo benefício. No presente trabalho foi proposto o desenvolvimento de um cateter implantável de monitorização de pressão intracraniana do tipo micro transdutor strain-gauge. Foram construídos protótipos funcionais e submetidos a ensaios de desempenho, especificados em norma técnica para monitorização de pressão sanguínea, a influência da temperatura na medição de pressão, bem como a exatidão das medições. Os processos empregados no trabalho são utilizados comumente na indústria de encapsulamento de semicondutores, porém foram levadas em consideração as especificidades da aplicação, adequando as técnicas disponíveis às geometrias e materiais empregados, considerando a necessidade de utilização de materiais biocompatíveis. / The traumatic brain injury (TBI) is nowadays the third cause of death in the world. Recent studies have shown the intracranial pressure (ICP) monitoring as an important tool for cerebral perfusion pressure (CPP) calculation and cerebral blood flow (CBF) assestment, reducing significantly the mortality statistics. Besides TBI, several others pathologies and neurosurgery conditions have been using the ICP monitoring technique. The proposal of ICP monitoring first appeared on the 50’s, where a tube fulfilled with fluid in contact with cerebrospinal fluid (CSF) was introduced into the intracranial space and connected to an external pressure transducer. With the waves of the microelectronics and microelectromechanical systems (MEMS) industry evolution, it was possible to put the transducer and all the electronics inside the catheter tip, allowing a less invasive monitoring, decreasing the risk of infection. The state of art catheters with micro transducer on the tip can be divided into three groups: strain-gauge, optical fiber and pneumatic. Each group has it’s own characteristics, however the first has been demonstrated as the rugged solution, being reliable, cost effective and with good accuracy. In the present work, it was proposed the development of an strain-gauge micro transducer implantable catheter for intracranial pressure monitoring. Functional prototypes were built and submitted to performance tests, according to the technical standards in the medical equipment area, the temperature influence over the pressure measurements was evaluated, as well as the accuracy. The adopted processes are commonly used in the semiconductor packaging industry, however it was considered the application special requirements, adapting the processes to the geometry and materials used, considering the needs of biocompatible materials.

Die Höhe des optimalen zerebralen Perfusionsdruckes nach schwerem Schädel-Hirn-Trauma wird kontrovers diskutiert. Während im sogenannten Lund-Konzept ein niedriger Perfusionsdruck angestrebt und die Gabe von Katecholaminen aufgrund potentieller zerebraler vasokonstringierender und weiterer Nebeneffekte vermieden wird, befürwortet das CPP-Konzept nach Rosner eine Anhebung des zerebralen Perfusionsdruckes, wenn notwendig unter intravenöser Gabe von Katecholaminen. Vor diesem Hintergrund galt es, in einem experimentellen Schädel-Hirn-Trauma- Modell der Ratte (Controlled Cortical Impact Injury) den Bereich des optimalen zerebralen Perfusionsdruckes nach traumatischer Hirnkontusion zu ermitteln und den Effekt von Katecholaminen auf den posttraumatischen zerebralen Blutfluss und die Entwicklung des sekundären Hirnschadens zu untersuchen. Die wesentlichen Ergebnisse dieser Arbeit lassen sich wie folgt zusammenfassen: In der Akutphase nach Hirnkontusion liegt der Bereich des zerebralen Perfusionsdruckes, welcher die Entwicklung des Kontusionsvolumens nicht beeinflusst, zwischen 70 und 105 mm Hg. Eine Senkung des Perfusionsdruckes unterhalb bzw. Anhebung oberhalb dieser Schwellenwerte vergrößert das Kontusionsvolumen. Die Anhebung des Blutdruckes mittels intravenöser Infusion von Dopamin oder Noradrenalin führt sowohl in der Frühphase als auch in der Spätphase nach Trauma (4 Stunden bzw. 24 Stunden nach kortikaler Kontusion) zu einem signifikanten Anstieg im kortikalen perikontusionellen Blutfluss und in der Hirngewebe-Oxygenierung. Die durch Anhebung des zerebralen Perfusionsdruckes auf über 70 mm Hg induzierte Verbesserung des posttraumatischen zerebralen Blutflusses bewirkte jedoch keine Reduzierung der Hirnschwellung. Für eine Katecholamin-induzierte zerebrale Vasokonstriktion nach kortikaler Kontusion gibt es keinen Anhalt. Um die Entwicklung des sekundären Hirnschadens nach kortikaler Kontusion zu minimieren, sollte der zerebrale Perfusionsdruck nach traumatischem Hirnschaden nicht unterhalb 70 mm Hg liegen. Eine Anhebung des Perfusionsdruckes auf über 70 mm Hg erscheint nicht notwendig oder vorteilhaft zu sein. Wenn notwendig, kann sowohl in der Früh- als auch Spätphase nach Trauma der zerebrale Perfusionsdruck mittels intravenöser Gabe von Katecholaminen angehoben werden. / The optimum cerebral perfusion pressure after severe traumatic brain injury remains to be controversial. In the Lund concept a relatively low cerebral perfusion pressure is preferred, and administration of catecholamines is avoided due to potential catecholamine-mediated cerebral vasoconstriction and other side effects. In contrast, the CPP concept of Rosner recommends elevation of cerebral perfusion pressure, if needed by intravenous administration of catecholamines. Based on this, in an experimental model of traumatic brain injury of the rat (Controlled Cortical Impact Injury) the optimum range of cerebral perfusion pressure after traumatic brain contusion and the effects of catecholamines on posttraumatic cerebral perfusion and development of secondary brain injury were investigated. The most significant results can be summarized as follows: In the acute phase after brain contusion the range of cerebral perfusion pressure that does not affect the development of posttraumatic contusion volume was found to be between 70 and 105 mm Hg. Reduction of the cerebral perfusion pressure below or elevation above these thresholds increases contusion volume. Elevation of blood pressure by intravenous infusion of dopamine or norepinephrine during the early (4 hours) as well as late (24 hours) phase after trauma results in a significant increase in pericontusional blood flow and brain tissue oxygenation. The increase in cerebral blood flow by elevating cerebral perfusion pressure above 70 mm Hg did not decrease cerebral edema formation. There was no evidence of a catecholamine-induced cerebral vasoconstriction after cortical contusion. In order to minimize secondary brain injury after cortical contusion, cerebral perfusion pressure should not fall bellow 70 mm Hg. However, a further active elevation of cerebral perfusion pressure does not appear necessary or beneficial. If needed cerebral perfusion pressure can be elevated by administration of catecholamines in the early as well late phase after trauma.