Syfte och frågeställning Syftet med studien var att undersöka sambandet mellan hjärtfrekvens (HF), skattad ansträngning samt syreupptag i jämförandet av två arbetsformer; ergometercykel och steplåda. Frågeställning var: hur ser sambandet ut mellan arbetseffekt och HF samt skattad ansträngning för de två arbetena på de givna submaximala effektnivåerna 75 Watt, 125 W samt 175 W. Studien har även för avsikt att jämföra den skattade ansträngningen på ergometercykel kontra den på steplåda vid försök att uppnå maxpuls. Vidare att jämföra den beräknade maximala syreupptagningsförmågan vid Rhyming & Åstrands steptest med den beräknade maximala syreupptagningsförmågan för denna studies modifierade Åstrandstest på ergometercykel. Dessa jämförs sedan med den bestämda maximala syreupptagningsförmågan på ergometercykel. Metod Datainsamlingen har skett genom att 16 testpersoner, åtta kvinnor och åtta män, utfört två maximala tester, ett On-linetest på ergometercykel Monark Ergomedic 839E där utandningsluften analyserades i blandningskammmare (Oxycon Pro, Jaeger GmbH) och ett på steplåda där enbart HF och skattad ansträngning registrerades med pulsklockan Polar Accurex plus och enligt Borgs RPE-skala, samt två submaximala tester, ett per redskap. Resultat Vid jämförelse av de två arbetena vid samma givna effekt var testpersonernas HF högre på samtliga submaximala effektnivåer. Testpersonernas upplevda ansträngning, enligt Borgs RPE-skala, var lika på både cykeln o steplådan om testpersonerna skattade 11 eller lägre. Skattade testpersonerna högre än 11 så upplevdes steplådan som mer ansträngande än arbetet på cykeln. Vid sammanställningen av resultaten för testpersonernas olika maximala test på cykel kontra steplåda var skillnaden i HF i medeltal liten. Diskussion och konklusion Möjlig orsak till att HF och skattad ansträngning var högre för arbetet på steplåda än cykel kan antas vara kraftåtgång. Arbete på steplåda sker vertikalt där acceleration krävs för varje steg upp på steplåda, och där kraft krävs vid inbromsning (excentriskt arbete) vid steg ned från steplåda. Troligtvis är detta mer energikrävande än att upprätthålla en konstant rörelse vid given belastning på cykel. På cykel sker arbetet i en stabilare position samt att energin i cykelns svänghjul hjälper testpersonen att upprätthålla den kraft som krävs för att uppnå given effekt.

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digitalisering@umu

Fatty acid composition in the body displays a high level of heterogeneity and can rapidly respond to changes in diet regime or to starvation. Homeostasis of the level of certain fatty acids is an important factor for maintenance of structural integrity as well as for proper signaling within the organism. Hence, changes in fatty acid composition have been proposed as an important factor during the pathogenesis of many diseases.Concentration of polyunsaturated fatty acid (PUFA) within the body is modulated by the interplay between dietary intake, endogenous de novo synthesis or mobilization of fatty acids from tissue reservoirs. Endogenous synthesis of PUFA is regulated on different genetic levels as well as the level of substrate availability. Studies have reported a variation in PUFA biosynthesis between different developmental stages, age, gender, during pregnancy, lactation and under conditions of certain disorders. A member of the enzymatic machinery involved in PUFA synthesis is the elongase Elongation of very long-chain fatty acids 2 (ELOVL2) that controls the elongation of PUFA with 22 carbons to produce 24 carbons precursors for the production of the omega-3 PUFA, docosahexaenoic acid (DHA, 22:6n3) and the omega-6 PUFA, docosapentaenoic (DPAn6, 22:5n6). Deletion of Elovl2 in a mouse model (Elovl2KO) leads to systemic DHA deficiency at different physiological and early lifestages, and is related to certain metabolic dysfunctions. Mitochondria of Elovl2KO mice display structural and functional impairment. Compared to wild type littermates, Elovl2KO mice do not gain as much weight after high-fat diet treatment and do not develop hepatic steatosis, despite having a higher level of the positive regulator of denovo lipogenesis, nuclear transcription factor SREBP1c. Resistance to high fat diet induced-obesity in Elovl2KO mice is abolished by DHA supplementation together with high sucrose content in the background diet. In conclusion, deletion of Elovl2 in mice leads to systemic DHA deficiency that has pleiotropic effect on mouse energy metabolism. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript. Paper 4: Manuscript.</p>

It is well known that the outcome of teaching and learning in higher education is often unsatisfactory. Earlier studies have shown that medical students often have a surface approach to their studies and that misconceptions of fundamental physiological phenomena are common. The aim of this thesis is to support educational practice in medicine, particularly in medical physiology. The thesis can be categorised as subject matter-specific education research, which means that questions about teaching and learning are closely linked to the subject studied. The researcher should be well acquainted with the subject in question. The subject area dealt with in this thesis is physiological phenomena related to cardiovascular pressure-flow relations. The thesis consists of studies of 3-dimensional intra cardiac pressure-flow phenomena in the heart (studies 1 and 2) and studies of how students conceive of and develop an understanding of physiological phenomena related to blood pressure and blood pressure regulation (studies 3 and 4). Flow in the left atrium as well as inflow-patterns to the left ventricle were studied. The 3-dimensional method elucidates vortical flow phenomena which were previously unknown. The findings could contribute to increasing physicians and technicians understanding of flow phenomena in the diagnosis and assessment of heart disease and to the further development of diagnostic methods. In the studies of learning and understanding of physiological phenomena, the findings point to new aspects of a deep approach to learning, which have to do with the students’ ability to change perspective and adopt a variety of learning strategies to a phenomenon (Moving) versus a tendency to hold on to one explanatory model (Holding). The study also investigates the students’ ability to identify and apply fundamental physiological principles as well as how they conceive of the importance of detailed knowledge for understanding of physiology. The findings point to differences in the students’ conceptions of physiological principles. A problemising approach, which includes not only causally described relations, indicates a more complex conception of physiological phenomena. The study shows aspects of understanding which are seldom assessed in examinations. The findings indicate a connection between the students’ approaches to learning and the quality of their understanding of fundamental physiological principles. In the thesis, teaching interventions are proposed in order to stimulate dynamic learning and a learning environment where students are not afraid to challenge their conceptions in order to acquire a rich and nuanced picture of physiological phenomena.

<p>Syfte och frågeställningar</p><p>Syftet var att jämföra fysiskt arbete i rumstemperatur och arbete under värmepåverkan, för att därigenom undersöka hur fysiskt arbete i värme påverkar kroppen i ett fysiologiskt perspektiv. Mina frågeställningar var: Hur påverkas hjärtfrekvens, kroppstemperatur och vätskeförlust vid submaximalt arbete i värme? Hur påverkas hjärtfrekvens, kroppstemperatur och vätskeförlust vid rökdykning? Hur påverkas hjärtfrekvens samt laktat- och glukoskoncentration i blodet vid arbete i värme jämfört med rumstemperatur?</p><p>Metod</p><p>Sex brandmän genomförde vid tre olika tillfällen fyra tester. Syreupptagningstest på cykel, (submax och max) i rumstemperatur, ett rökdykartest under värmepåverkan och ett submaximalt cykeltest i bastu. Syreupptagningsförmåga, hjärtfrekvens samt laktat- och glukoskoncentrationer i blod mättes under cykeltesterna i rumstemperatur. Vid rökdykartestet och cykeltestet i bastu mättes hjärtfrekvens, vätskeförlust, kroppstemperatur samt laktat- och glukoskoncentrationer.</p><p>Resultat</p><p>Hjärtfrekvensen vid rökdykartestet var 174 ± 7,7 slag/min (93 ± 1,4 % av max hjärtfrekvens på ergometercykel). Vätskeförlusten uppmättes till 1,1 ± 0,1 % av kroppsvikten, kroppstemperaturen höjdes med 2,1 ± 1,2 °C. Glukoskoncentrationerna i blod ökade mer jämfört med maxtest på cykel, startvärde 5,04 ± 0,59 jmf. 5,64 ± 1,00 mmol/l samt 2 min efter testet 6,79 ± 1,26 jmf. 6,46 ± 1,25 mmol/l. Vätskeförlusten vid cyklingen i bastu var 0,6 ± 0,1 % av kroppsvikten, kroppstemperaturen höjdes med 0,8 ± 0,3 °C. Vid cykling i bastu var laktatkoncentrationen i blod signifikant lägre än vid cykling i rumstemperatur 1,23 ± 0,17 mmol/l jmf. 3,43 ± 1,46 mmol/l (175W).</p><p>Slutsats</p><p>Under rökdykartestet hade försökspersonerna en genomsnittlig hjärtfrekvens som låg nära den maximala hjärtfrekvensen som uppmättes under ergometercykeltestet. Stora fysiologiska krav ställs på brandmän vid rökdykning eftersom de under en tidsperiod av 13-18 min ligger på en hög och jämn hjärtfrekvens under hela arbetet. Vid arbete i  85 gradig värme med full skyddsutrustning erhölls ingen skillnad i hjärtfrekvens jämfört med arbete i rumstemperatur. Vätskeförluster och förhöjda kroppstemperaturer beror på vilken sorts arbetsbelastning och värmegrad man utsätts för. Laktatkoncentrationerna vid arbete i  85 gradig värme var avsevärt lägre jämfört med samma arbete i rumstemperatur, vilket eventuellt berodde på den sänkta temperaturen på inandningsluften från luftpaketet, vilket ger ett ökat syreinnehåll. Glukoskoncentrationerna vid arbete i  85 gradig värme ändras inget i förhållande till samma arbete i rumstemperatur. Vid tyngre arbete i högre värme syns förhöjda koncentrationer efter arbetet.</p> / <p>Aim</p><p>The purpose was to compare physical work in a normal temperature to physical work during heat exposure and in that way investigate how physical work during heat exposure affects the human body in a physiological perspective. My questions were: How does submaximal work during heat, affect heart rate, water loss, body temperature, lactate level and blood glucose level? How does smoke-diving affect heart rate, water loss, and body temperature? How is the heart rate, lactate level and blood glucose level affected in work during heat exposure compared to work in a normal temperature?</p><p>Method</p><p>Six firefighters performed at three different occasions four tests. VO2 tests in cycle-ergometer (submaximal and maximal) in a normal temperature. A smoke-diving test during heat exposure and a submaximal cycle test in a sauna. VO2, heart rate, lactate level and blood glucose level was measured during the tests in the normal temperature. Heart rate, water loss, body temperature, lactate level and blood glucose level was measured during the smoke-diving test and the submaximal cycle test in sauna.</p><p>Results</p><p>Mean heart rate during the smoke-diving test was 174 ± 7,7 bpm (93 ± 1,4 % of maximal heart rate attained in the cycle-ergometer test). Water loss measured to 1,1 ± 0,1 % from bodyweight, body temperature was increased with 2,1 ± 1,2 °C. The blood glucose levels were higher compared to the maximum test during cycling. Concentration at start was 5,04 ± 0,59 vs. 5,64 ± 1,00 mmol/l and 2 min after the test 6,79 ± 1,26 vs. 6,46 ± 1,25 mmol/l. Water loss during the submaximal cycling in sauna was 0,6 ± 0,1 % of bodyweight, body temperature were increased with 0,8 ± 0,3 °C. Lactate levels during the submaximal cycling in sauna were significant lower than cycling in a normal temperature 1,23 ± 0,17 mmol/l vs 3,43 ± 1,46 mmol/l (175W).</p><p>Conclusions</p><p>During the smoke-diving test the firefighters had a mean heart rate which was near the maximal heart rate attained in the cycle-ergometer test. The smoke-diving test was physically very demanding for the subjects since the tasks lasted in 13-18 min and the heart rate was in such high levels in general. During physical work in  85 °C wearing a self-contained breathing apparatus and fire-protective clothing, no difference in heart rate compared to work in a normal temperature could be measured. Water loss and increased body temperatures depends on which kind of physical work and heat exposure the firefighters was exposed to. Lactate levels during physical work in  85 °C was significant lower than the same work in a normal temperature. This might result from the cool air from the breathing apparatus, which lead to a higher oxygen uptake in the muscles. There were no difference in blood glucose levels during physical work in  85 °C compared to work in a normal temperature. After more physically demanding work during higher temperature, elevated levels was measured.</p>

Familial amyloidotic polyneuropathy (FAP), found in the northernmost counties in Sweden, is a rare, lethal and inherited amyloidosis. The disease is caused by mutated transthyretin (TTR). The mutation is characterized by an exchange of valine for methionine at position 30 (ATTRVal30Met). FAP is characterised by progressive polyneuropathy affecting both the peripheral and autonomic nervous system (ANS). Cardiac arrhythmia and autonomic disturbances are common as well as gastrointestinal symptoms: such as constipation and diarrhoea. Today, orthotopic liver transplantation (LTx) is the only treatment to stop the progression of FAP. The rationale for this is because 95% of TTR is synthesized by the liver, a liver transplantation should abolish the production of new mutated amyloidogenic TTR. The first liver transplantation for FAP was performed in Sweden 1990. Heart complications and autonomic disturbances are common in FAP patients both before and after liver transplantation. The aim of the present study was three-fold: to determine whether liver transplantation affects the natural course of cardiac arrhythmias and cardiac autonomic function; to predict the risk of ventricular arrhythmias; and to elucidate heart rate variability (HRV) patterns by power spectrum analysis and Poincaré plots. In total, ninety-seven Swedish FAP patients were included in the studies. The patients underwent 24-hours electrocardiography (Holter) recordings, and/or signal averaged electrocardiography (SAECG) and heart rate variability. The study showed that many patients developed cardiac arrhythmias and conduction disturbances after LTx. Approximately 25 percent of patients were pacemaker treated after LTx. The SAECG recordings disclosed that many FAP patients had ventricular late potentials (LP) compared with healthy subjects, and that LP were associated with nonsustained ventricular arrhythmia. Analyses of heart rate variability (HRV) showed reduced autonomic function in the majority of patients. Some patients had high HRV with broadband power spectra and Poincaré graphs with a fan or complex pattern. These novel findings could be an indicator of ECG abnormalities (subtle atrial arrhythmia) in FAP patients instead of reflecting normal cardiac autonomic modulation. The HRV studies also showed that LTx preserves cardiac autonomic function in FAP. In conclusion, cardiac arrhythmias, late potentials and reduced heart rate variability were common in Swedish patients with FAP, whether they underwent liver transplantation or not. The absence of LP may indicate a low risk for ventricular tachycardia in FAP patients.

Lipoprotein lipase (LPL) hydrolyses blood lipids at the vascular endothelium. This action makes fatty acids available for tissue metabolic requirements. LPL is anchored to the endothelium by electrostatic forces and may act as a bridge connecting lipoproteins to cell surfaces. Clusters of positively charged amino acid residues in LPL interact with anionic groups on oligosaccharides covering the cell surfaces. Heparin competes with cell surface oligosaccharides for binding to LPL. Interaction of LPL with soluble and cell surface- ound oligosaccharides influences the activity and catabolism of the enzyme. LPL has a dual role in the development of atherosclerosis. Hydrolysis of lipoproteins by LPL contributes to clearance of lipids from plasma, resulting in an anti-atherogenic lipid profile. On the other hand, trough its bridging function, LPL contributes to lipoprotein retention at the endothelium and in the connective tissue of the artery wall. Furthermore LPL may stimulate uptake of lipoproteins in cells, converting them to foam cells. In this way LPL is considered to be proatherogenic. We have investigated the effects caused by a synthetic heparin analogue, RG-13577, developed for treatment of tumors by anti-angiogenesis theraphy (Paper I) and by heparin (Paper II) on the turnover and biological role of LPL. The variation of LPL activity in kidney among animal species was studied in Paper III. Localization of LPL in healthy and atherosclerotic human arteries in relation to two other heparin-binding proteins (extracellular superoxide dismutase and apolipoprotein B) was studied in Paper IV.