| 1. |
- Berg, Marie, 1955
(författare)
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Genuine Caring in Caring for the Genuine : Childbearing and high risk as experienced by women and midwives
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The experience of pregnancy and childbirth is a central life event with special implications for women at high risk. This thesis describes the meaning of pregnancy, childbirth and midwifery care in four qualitative interview studies based on the lifeworld theory. Women were interviewed during pregnancy and within one week after childbirth. Midwives were interviewed concerning midwifery care for women at high risk. In an intervention study, childbirth experience as reported through a post partum questionnaire was compared between women receiving standard care and women who had formulated a birth plan preceded by a questionnaire on their expectations and feelings about childbirth.The findings emphasise that childbearing women at high risk live in an extremely vulnerable situation. The vulnerability is obvious in the use of an individual birth plan, where negative feelings become more frequent in women at high risk than in those with normal pregnancy and childbirth. During pregnancy the women feel a moral commitment towards the child, including feelings of objectification and of exaggerated responsibility. During an obstetrically complicated childbirth the essential meaning is the women’s desire to be recognised and affirmed as individual persons. Like women with normal pregnancy and childbirth, they need an emotionally present midwife who sees, give trust and supports.Good midwifery care of childbearing women at high risk is synthesised as "genuine caring in caring for the genuine". The ethos of caring constitutes the basis of caring. Women’s transition during pregnancy and childbirth is described as a genuinely natural process. Midwives have a special responsibility to encourage and preserve this process within women at high risk. The caring relationship is the core and the most essential tool in the care. Distinctive features in the midwifery care are embodied knowledge, physical as well as emotional presence, sensitivity, a mutual dialogue including shared control between midwife and woman, and confirmation and support of the genuine in each woman. The midwifery care is a struggle and a balance between natural and medical perspectives.
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| 2. |
- Göthberg, Sylvia, 1953
(författare)
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New modes of improving ventilation and oxygenation in pulmonary hypertension and acute respiratory failure in newborns and children
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pulmonary hypertension leading to hypoxemia is a potentially life-threatening condition in pediatric intensive care. Hypoxemia may also result from conditions not primarily related to pulmonary hypertension. The pediatric patients with these symptoms are:· Children after surgery on cardiopulmonary bypass with pulmonary hypertension attributable to congenital heart defects with high pulmonary blood flow.· Newborns with persistent pulmonary hypertension as a symptom of fetal illness or malformation or after a relapse into fetal circulation without obvious reason.· Children with acute respiratory failure and disturbed vascular/alveolar relation with atelectases and ventilation/perfusion mismatch with major pulmonary shunt.New methods to provide better ventilation and oxygenation have been developed over the last few years. The aims of the present thesis were to assess:· The effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on pulmonary hypertension and oxygenation in dose-response studies.· The effect of high frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on alveolar recruitment and response to iNO.· Respiratory inductive plethysmography during dynamic ventilatory changes on high frequency oscillatory ventilation and on conventional ventilation (CV) as a new continuous and non-invasive method to optimize alveolar recruitment without interrupting ventilation.· Possible residual cardiopulmonary and neurological symptoms in a follow-up study after treatment with inhaled nitric oxide.The methods used were dose-response studies with iNO, lung volume recruitment with surfactant, high frequency oscillatory ventilation and partial liquid ventilation, lung volume measurements with respiratory inductive plethysmography and a four-center follow up study after iNO.Results and conclusions:· iNO decreased pulmonary artery pressure after cardiopulmonary bypass. No dose response relationship was found in the dose range of 3-80 ppm nitric oxide. Only a low dose of inhaled nitric oxide was needed, 5 ppm or less, which also concomitantly improved oxygenation in postoperative pulmonary hypertension in children.· iNO in doses up to 20 ppm immediately improved oxygenation in 68% of children with acute respiratory failure. Only 29% of non-responders survived and no delayed response was found in patients with acute respiratory failure. Non-responders need careful attention in order to improve ventilation and/or hemodynamics. Otherwise they should be transferred without delay to extracorporeal membrane oxygenation when eligible for such treatment.· Follow up after iNO treatment showed residual pulmonary hypertension in cardiac but not in lung patients. Residual respiratory disease and neurodevelopmental delay were not increased as compared with previous studies or owing to improved survival of severely ill patients.· In severe respiratory distress syndrome in preterm lambs, rescue treatment with alveolar recruitment strategies, HFOV and PLV, resulted in improved oxygenation. Alveolar recruitment was improved, as indicated by further improvement in oxygenation in response to iNO, particularly when HFOV and PLV were combined. Mean airway pressures on HFOV and CV when combined with PLV were significantly lower, reducing the risk of alveolar barotrauma.· Respiratory inductive plethysmography could be used to assess changes in lung volume during HFOV and CV in term and preterm lambs. This method provided the means to monitor and optimize lung volume continuously, non-invasively and without interruption of ventilation during mechanical ventilation. Observed changes in lung volume predicted changes in oxygenation.
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| 3. |
- Iosif, Robert
(författare)
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Factors Regulating Neurogenesis in Intact and Pathological Brain: Role of TNF-alpha
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last decade it has been clearly demonstrated that the adult brain contains neural stem cells (NSCs) localized mainly in two regions: the subgranular zone in the dentate gyrus and the subventricular zone (SVZ) lining the lateral ventricles. In the intact brain, these NSCs give rise to new dentate granule cells and olfactory bulb neurons, respectively. Following a brain damage such as stroke and an epileptic seizure, the generation of new neurons (neurogenesis) in the hippocampus and the SVZ in adult rats, mice and probably humans is increased. The molecular mechanisms regulating the different steps of insult-induced neurogenesis (cell proliferation, survival, migration, and differentiation) are poorly understood. To learn more about the molecular mechanisms regulating neurogenesis we examined which factors in the epileptic and stroke generated environment that affects the newly formed neurons. In this thesis we explored the role of a prostaglandin and a cytokine in the hippocampus and subventricular zone, both during physiological conditions and after an insult. In the first paper we induced status epilepticus (SE) in rats by electrical stimulation in the hippocampus. We then compared the two different seizure grades, partial status epilepticus (pSE) and generalized status epilepticus (gSE), in order to identify factors in the microenvironment which are differentially regulated by SE severity and may underlie differences in neurogenesis. We particularly addressed the question whether SE severity differentially affects the expression of prostaglandin E2 (PGE2), cyclooxygenase (COX-2), the enzyme catalyzing the first committed step in PGE2 synthesis, and the brain-derived neurotrophic factor (BDNF). In conclusion, the results from paper I showed clear differences between pSE and gSE rats in hippocampal PGE2 and BDNF levels 7 days after SE. We found no evidence that the high levels of PGE2 and BDNF, in rats exhibiting pSE, during the first days after SE are of major importance for the survival of new neurons during the first days after formation. In the second study, we developed a new SE model for mice based on continuous electrical stimulation in the hippocampus, as done previously in rats. We then investigated whether the cytokine, tumor necrosis factor alpha (TNF-α), could influence neurogenesis. TNF-α is a well-known proinflammatory factor and we speculated that the detrimental action of inflammation on insult-induced neurogenesis might be caused by TNF-α. It had also been shown that NSCs themselves express TNF-α, which raised the possibility of an autocrine action involved in neurogenesis. We used transgenic mice with various genetic manipulations of TNF-α signaling to determine the influences on neurogenesis under physiological conditions and following a brain insult. Taken together, the results from paper II demonstrate the involvement of TNF-R1 and TNF-R2 signaling in the regulation of adult hippocampal neurogenesis, and that signaling through the two different receptors have differential actions on neurogenesis. Our data indicate that TNF-α can modulate the formation of new neurons both under physiological and pathological conditions by acting on these two receptors with differential effects on proliferation and survival, with TNF-R1 as the key mediator of TNF-α signaling. In the final study we examined whether signaling through TNF-R1 could influence progenitor proliferation in another neurogenic area during physiological conditions and following a pathological condition such as stroke and SE. We used the same transgenic mice to study TNF-α and its effects on the formation of new neurons in the SVZ. We found that mice lacking TNF-R1 function responded to stroke with enhanced SVZ cell proliferation and thereby that TNF-R1 signaling mediates a suppressant effect on the proliferation of progenitor cells. Following stroke TNF-R1 acts as a negative regulator on the progenitor proliferation. In contrast, deletion of TNF-R1 did not influence basal cell proliferation in SVZ. Further, loss of TNF-R1 function had differential effects on SVZ cell proliferation following the two pathological conditions SE and stroke and we did not find any differences in cell proliferation after SE. Although both insults gave rise to increased cell proliferation in the SVZ, the dampening action of TNF-R1 on proliferation was revealed only after stroke. Taken together, the results from paper II and III suggest that suppression of TNF-R1 signaling might be a strategy to promote the proliferative response in the SGZ after SE and in the SVZ after stroke, to stimulate neurogenesis in the adult brain. However, it will be important to establish how such an approach will affect other steps of neurogenesis and the functional outcome after both SE and stroke. There could be a positive therapeutic potential of neurogenesis from endogenous stem cells after brain insults. However, we need to know much more about the regulation of neurogenesis in order to make this response more effective. The current thesis work aims at elucidating some of the mechanisms of neuronal self-repair, which could have implications for the development of stem cell-based approaches for the treatment of brain disorders.
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| 4. |
- Steffensen, Rudi, 1961
(författare)
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Molecular genetics of human carbohydrate defined blood groups. Studies of the ABO and P blood group systems
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to explore the molecular genetics of the carbohydrate defined blood group ABO and P systems.The blood group ABO system is the clinically most significant system in transfusion medicine. Using modern molecular biology, a number of the ABO alleles have been characterized. The phenotypes associated with these alleles have been shown to be a consequence of point mutations or deletions leading to (presumed) inactive or partly inactive glycosyltransferases. At the onset of this project, analysis of the ABO genes was hindered by lack of knowledge of the genomic organisation. The first part of this study therefore deals with the genomic organisation of the coding region, which was found to span seven exons. During our studies a new blood group O allele, designated O2 was identified. This new allele has a different inactivation mechanism than previously identified O alleles.The second part of this study aimed at gaining insight into the molecular genetics of the P blood group system, which is the last of the carbohydrate defined blood group systems to be elucidated. Using modern bioinfomatics and data from the human genome resources a gene, homologous to a new a4GlcNAc-transferase located on chromosome 3p14.3, was identified, cloned and expressed. The novel gene encoded an enzyme with Pk activity and a single homozygous missense mutation M183K was found in six Swedish individuals with the rare p phenotype. The mutant gene was inactive confirming that this gene represented Pk synthase. Although the gene appears to colocalize on chromosome 22 with the previously P1 polymorphism, the expressed enzyme did not function as a P1 synthase. The implications for the P1 genotype are discussed.
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| 5. |
- Bazargani, Farhan, 1969
(författare)
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Acute inflammation in peritoneal dialysis. Experimental studies in rats. Characterization of regulatory mechanisms.
- 2005
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Ingår i: Swedish Dental Journal. Supplement. - Göteborg : Göteborg University. - 0348-6672. ; 171, s. 1-57
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The predominant problems associated with peritoneal dialysis (PD) are ultrafiltration failure and peritonitis. PD maintains a state of intraperitoneal inflammation that affects the structure and function of the peritoneal membrane, potentially impairing ultrafiltration efficiency. Paradoxically, some PD fluids also have anti-inflammatory properties that may compromise the immune defense against peritonitis. This anti-inflammatory feature is mostly due to the glucose degradation products (GDPs), formed during heat-sterilization and storage of PD fluids. The main purpose of the present thesis was to study regulatory mechanisms behind the acute intraperitoneal inflammatory response in PD in the presence and absence of experimental peritonitis. Rats were exposed to a single dose of heat- or filter sterilized PD fluids either as an i.p. injection or as an infusion through an indwelling catheter, with or without supplementations, or pretreatment of the animals. The dwell fluid was analyzed zero, two and four hours later concerning activation of the complement and coagulation cascades, neutrophil recruitment and respiratory burst, ultrafiltration volumes, cytokine-induced neutrophil chemoattractant (CINC-1), rat mast cell protease 2 (RMCP-2), glucose, urea and histamine concentrations and ex vivo/in vitro intraperitoneal chemotactic activity.Exposure to filter sterilized PD fluid alone induced intraperitoneal complement activation and coagulation, neutrophil recruitment and increased the levels of CINC-1 during the dwell. Intraperitoneal concentrations of the mast cell markers histamine and RMCP-2 changed little during the dwells and did not indicate mast cell activation. Low molecular weight heparin (LMWH) and C5 blockade improved ultrafiltration. Pretreatment with cobra venom factor, known decomplementing agent, blocked the CINC-1 release and the neutrophil recruitment and improved ultrafiltration. In combination with experimental peritonitis, heat sterilized PD fluid compared to filter sterilized, inhibited the CINC-1 release and the recruitment of neutrophils to the peritoneal cavity without affecting the intraperitoneal complement activation.The results of the present thesis indicate that addition of LMWH to the PD fluid improves ultrafiltration, probably by blocking C5a activity. C5 blockade seems to improve ultrafiltration by a mechanism that involves a reduction in glucose transport, possibly by reducing C5 induced vasodilation. Complement activation is an early step in the acute reaction to PD and probably mediates the downstream events that lead to the recruitment of inflammatory cells to the peritoneal cavity. The cells involved in the release of CINC-1 later in this sequence are probably the mesothelial cells. During experimental peritonitis, heat sterilized PD fluids inhibited the neutrophil respiratory burst response of intraperitoneal neutrophils. Heat sterilized PD fluids also inhibit the recruitment of neutrophils to the peritoneal cavity by a mechanism independent of complement activation but probably depending on cytokine CINC-1 release during peritonitis.
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| 6. |
- Sävman, Karin, 1960
(författare)
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Perinatal brain injury - markers and mediators. Non-protein-bound iron and pro-inflammatory cytokines in newborn infants and neonatal pigs
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Two groups of newborn infants have an increased risk for perinatal brain injury; preterm infants and term infants subjected to birth asphyxia. Experimental studies indicate that hypoxic-ischemic insults in the perinatal period initiate a secondary neurotoxic cascade including formation of toxic reactive oxygen species as well as an inflammatory response with elevated levels of potentially neurotoxic cytokines. In the preterm infant a fetal inflammatory response to maternal infection is also directly implied in the development of brain injury and immature white matter exhibits an intrinsic vulnerability to oxidative injury. Non-protein-bound iron (NPBI), measured by a new spectrophotometric method, is a potent pro-oxidant through its capacity to catalyze the formation of the highly toxic hydroxyl radical.The aims of the study were to evaluate: (a) inflammatory activation expressed as pro-inflammatory cytokines in CSF from infants with birth asphyxia as well as preterm infants with posthemorrhagic ventricular dilatation (PHVD) and subsequent high risk for white matter injury. (b) extracellular levels of NPBI in different areas of the brain under normal conditions as well as during hypoxia and reoxygenation in newborn piglets. (d) the content of NPBI in CSF from preterm infants with PHVD.CSF was obtained from asphyxiated term infants and term control infants within 72 h from birth and from preterm infants with PHVD and preterm control infants approximately two weeks after birth. Newborn piglets were subjected to hypoxia-reoxygenation according to a model that produces clinical encephalopathy and neuropathological changes similar to those seen in term asphyxiated infants. Samples for NPBI analysis were obtained by microdialysis probes inserted into vulnerable parts of the piglet brain.There was a significant increase of the pro-inflammatory cytokines IL-6 and IL-8 in CSF after birth asphyxia. IL-6 and IL-8 levels correlated with the degree of encephalopathy and IL-6 correlated with outcome. The CSF levels of IL-1b, IL-6, IL-8, and TNF-a were elevated in infants with PHVD. NPBI was detected in all examined areas of the piglet brain under normal conditions and increased during early reoxygenation after hypoxia. NPBI was detected frequently and at high levels in CSF from infants with PHVD. Conclusions: Birth asphyxia elicits an inflammatory response with elevated pro-inflammatory cytokines in CSF and elevated cytokine levels are associated with severe clinical course and abnormal outcome. Preterm infants with PHVD exhibit an intense inflammatory response in CSF weeks after the original insult, but at this late time-point no correlation with morphological brain injury or outcome is found. NPBI is present in brain extracellular space under normal conditions and increases during reoxygenation after hypoxia. NPBI is also elevated in CSF from infants with PHVD. Elevated levels of NPBI imply impaired iron-regulation and an increased risk for oxidative injury
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| 7. |
- Ericsson, Ylva
(författare)
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Knee function, Physical Activity and Perceived Health after Meniscectomy in the Middle-aged
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to explore the impact of meniscal injury and meniscectomy on joint and muscle function, physical activity and perceived health in middle-age subjects and to evaluate the effect of a functional exercise program. Male and female post meniscectomy patients participated in Studies I-IV (n=45 in Studies I-III, n=99 in Study IV) and Study IV also included 94 controls. Outcome measures were thigh muscle strength, functional performance tests, femoral cartilage quality (assessed by dGEMRIC) and Body Mass Index (BMI) in addition to four questionnaires: the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Knee Self Efficacy Scale (K-SESABC), the Physical Activity Scale (PAS) and the MOS Short Form-36 (SF-36) health scale. Studies I-II revealed that patients had less strength in the operated compared to the nonoperated leg (mean difference 9%) and the deficit was associated with symptoms and functional limitations (KOOS). Cartilage quality (dGEMRIC Index) in the medial compartment was 14% lower than in the lateral, and correlated positively with thigh muscle strength/BW and negatively with BMI. In study III, patients were randomized to a four- month functional exercise intervention or to no intervention. The exercise group tolerated the training well and improved in one-leg hop, hamstrings strength and quadriceps endurance. In study IV patients scored lower than controls in K-SES and in two SF-36 subscales. Only 46% of the patients had resumed their pre-injury PA level, although current PA did not differ between the groups. In the patient group, K-SES was associated with PAS (rs=0.42) and SF-36 (rs= 0.35-0.85). Female patients scored lower than male patients in K-SES and four SF-36 subscales. In conclusion, patients were found to have considerable symptoms, functional limitations and lower self efficacy than controls 3-4 years after meniscectomy. Strong thigh muscles seem to be helpful for improving knee function and protecting knee cartilage, whereas high BMI appears to be harmful to the cartilage. Functional exercise training after meniscectomy could be a useful method for restoring knee function, thus helping patients to resume PA and maintain good health.
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| 8. |
- Nijm, Johnny, 1969-
(författare)
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Inflammation and cortisol response in coronary artery disease
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is characterized by a chronic inflammation, involving autoimmune components, in the arterial wall. An increase in proinflammatory activity relative to anti-inflammatory activity is considered to cause a progression of the disease towards plaque instability and risk of atherothrombotic events, such as acute coronary syndrome (ACS). Cortisol, the end product of the hypothalamus-pituitary-adrenal (HPA) axis, is a powerful endogenous anti-inflammatory mediator. Disturbances in the HPA axis have been reported in chronic inflammatory/autoimmune diseases, like rheumatoid arthritis. The aim of this thesis was to study various markers of systemic inflammation in patients with acute and stable conditions of coronary artery disease (CAD) and relate these findings to the cortisol response.Both patients with ACS and patients with stable CAD had high levels of C-reactive protein (CRP), interleukin (IL)-6 and IL-1 receptor antagonist, compared with healthy controls. In addition, patients with stable CAD had significantly more neutrophil-platelet aggregates than controls, as a possible indicator of neutrophil activation.The cortisol response was determined in two different cohorts of CAD patients; one consisting of patients with a first-time myocardial infarction and one consisting of patients with long-term stable CAD. From the acute phase to 3 months, the patients with a myocardial infarction showed a higher 24-h cortisol secretion and a flattened diurnal slope caused by higher cortisol levels in the evening, as compared with healthy controls. The patients with long-term stable CAD showed similarly high levels of cortisol in the evening. The levels of evening cortisol were strongly correlated with CRP and IL-6. When exposed to acute physical or acute psychological stress at 3 months, the ACS patients showed a markedly blunted cortisol response compared with healthy controls. Following the stress tests, a significant increase in CRP was observed in the patients but not in the controls, indicating a failure of the HPA axis to compensate for stress-induced inflammation in CAD.In the ACS patients, the time course of matrix metalloproteinases (MMPs) and their tissue inhibitor TIMP-1 was determined during the 3 months follow-up. A major finding was that the MMP-9 and TIMP-1 levels remained significantly higher in the patients at all time points compared to the controls. MMP-9 and TIMP-1, but not MMP-2, MMP-3 or MMP-7, were related to inflammatory activity, as assessed by CRP and IL-6. MMP-9 and TIMP-1 showed significant correlation with evening cortisol, even after adjustment for CRP and IL-6, lending further support for a link between ´high´ flat cortisol rhythm and systemic inflammatory activity.The activation status of neutrophils in stable CAD was further examined by measuring the expression, affinity state and signalling capacity of b2-integrins and the innate production of reactive oxygen species (ROS). However, the neutrophils in patients were not more activated in vivo than were cells in healthy controls, neither were they more prone to activation ex vivo. The data rather indicated an impaired function of neutrophils in stable CAD.The neutrophils in CAD patients showed a significantly lower number of total glucocorticoid receptors (GRs) and a lower GRa:GRb ratio compared to healthy controls, indicating a chronic over activation of the HPA axis and, possibly, a state of glucocorticoid resistance. Moreover, the evening cortisol levels in patients were associated with an overexpression of annexin-1, the ´second messenger´ of glucocorticoid action. In contrast to neutrophils in controls, the neutrophils in patients also showed a hyper responsiveness to exogenous annexin-1 resulting in impaired neutrophil function.To conclude, clinically stable CAD was associated with a systemic inflammatory activity, involving a high MMP-9:TIMP-1 ratio and an increased inflammatory response to acute stress but not any activation of neutrophils. This inflammatory activity was associated with a dysregulated cortisol secretion, defined by a flat diurnal rhythm and a blunted cortisol response to stress. Although the clinical relevance remains to be verified, an intriguing hypothesis is that a hyporesponsive HPA axis favours the development towards plaque instability.
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| 9. |
- Zachrisson, Helene, 1964-
(författare)
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Noninvasive assessment of cerebral circulation before, during and after carotid surgery
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Non-invasive ultrasound investigations were evaluated in patients with carotid artery stenosis in comparison with radiological disease gradations and perioperative blood pressure measurements. The aim was to assess cerebrovascular hemodynamics before, during and after carotid thrombendarterectomy (CEA) in relation to the clinical outcome of the surgical intervention.Intracranial collateral blood flow as a consequence of high grade carotid artery disease can be investigated by means of blood flow velocity measurements with 3D-transcranial Doppler flow mapping and proximal common carotid artery compressions. The value and risks of common carotid artery compression were therefore assessed. No adverse effects were seen in 3383 patient studies retrospectively reviewed. In addition, we found that transcranial Doppler without carotid compression may lead to false identification of the posterior cerebral artery.Preoperative blood flow velocities within the carotid stenosis and poststenotic blood pressures during intraoperative carotid clamping were analysed with respect to some serious postoperative complications. We found that blood flow velocities within severe internal carotid artery (ICA) stenoses are inversely related to the poststenotic collateral blood pressure. High diastolic blood flow velocities within the ICA stenosis might indicate low collateral blood pressures and increased risk for severe postoperative neurological complications. The discrepancies occasionally seen between preoperative ultrasound investigation and angiography might therefore be explained by high collateral backpressures, which may induce unusually low blood flow velocities within severe ICA diameter reductions.The carotid compression test, performed during the preoperative transcranial Doppler investigation, was used to predict middle cerebral artery (MCA) blood flow reductions during intraoperative carotid artery cross-clamping. Surprisingly, we found a greater decrease of the MCA blood flow velocities during the carotid compression test compared with the flow changes during cross-clamping. Signs of cerebrovascular autoregulation due to carotid compression were not reproducible during carotid clamping under general anaesthesia. The few patients with postoperative adverse reactions happened to show a pattern of low collateral blood pressures and relatively high MCA blood flow velocities during cross-clamping. Since general anaesthesia affects cerebral autoregulation we performed a postoperative transcranial Doppler study to assess the MCA blood flow pattern after surgical restoration of normal ICA blood flow. In the majority of the patients, we observed increased blood flow velocities bilaterally within the MCA, which might be a result of postoperative hyperperfusion or autonomic imbalance of carotid sinus baroreceptors.In conclusion, evaluations of cerebrovascular hemodynamics in CEA patients might give important information indicating risks of complications.
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| 10. |
- Cunha Goncalves, Doris
(författare)
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Levosimendan in early experimental sepsis: effects on the heart and hepatosplanchnic circulation
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis-related cardiovascular dysfunction associated with fluid-unresponsive tissue hypoperfusion might require inotropic treatment. This cardiovascular dysfunction seems to involve calcium desensitization and adrenergic unresponsiveness. We investigated the effects of clinically relevant plasma concentrations of the calcium sensitizer levosimendan during the first 6 h of endotoxemia in a model of experimental sepsis in pigs (21.8-44.0 kg). Levosimendan given to endotoxemic pigs receiving moderate volume resuscitation elicited tachycardia, hypotension and myocardial ischemia, as evidenced by a negative myocardial lactate flux (study I). Likewise, compared to non-treated controls, levosimendan did not improve systemic or hepatosplanchnic perfusion during endotoxin shock: the animals developed signs of tissue hypoperfusion with elevated blood lactate and low oxygen venous saturations (study II). Aggressive volume resuscitation before levosimendan treatment induced a hyperdynamic state that was sustained by levosimendan and norepinephrine treatment, whereas control animals gradually developed shock. Nevertheless, splanchnic blood flow was redistributed and the superior mesenteric artery, the hepatic artery and the portal vein blood flows (PVF) decreased. Similarly to study II, there were signs of systemic and hepatosplanchnic tissue hypoperfusion. In contrast, administration of dobutamine and norepinephrine, increased cardiac output (CO) and oxygen delivery, maintained PVF and improved tissue perfusion (study III). Load independent measurements of cardiac function showed that systolic function was actually enhanced during the first 2 h of sepsis, whereas diastolic function was depressed in both ventricles. The initial decrease seen in CO was a result of volume depletion, and recovered with aggressive volume resuscitation. Although endotoxin-induced lung injury caused early right ventriculovascular uncoupling and increased right ventricular (RV) myocardial oxygen demand, right coronary artery blood flow improved markedly with resuscitation, maintaining adequate myocardial perfusion (study IV). In resuscitated septic pigs, levosimendan supported RV function by increasing RV contractility at a low energy cost. CO and left ventricular ejection fraction increased, and right ventriculovascular coupling and mechanical efficiency tended to improve (study V). In conclusion, early treatment with levosimendan during resuscitated sepsis can increase CO and improves RV contractility at a low energy cost, but it does not improve hepatosplanchnic perfusion significantly, which is better achieved with dobutamine-norepinephrine. In addition, because levosimendan is an inodilator, its use in sepsis should be restricted to thoroughly fluid-resuscitated subjects.
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