Translation of heart failure with preserved ejection fraction: a tale of mice and men

Heart failure with preserved ejection fraction (HFpEF) represents a significant health concern with limited treatment options. This thesis addresses the challenges associated with developing pre-clinical models for HFpEF and delves into exploring the underlying disease mechanisms. The thesis proposes a comprehensive translational research approach aimed at enhancing the understanding of HFpEF and expediting the development of novel treatment strategies.Initially, the thesis proposes guidelines for designing HFpEF mouse models intended to more accurately mimic HFpEF in humans. These models take into account factors such as age, sex, and comorbidities often associated with HFpEF, such as obesity and type 2 diabetes mellitus (T2DM). Subsequently, the thesis describes the successful development of a new mouse model that closely resembles the HFpEF observed in humans. This model incorporates multiple factors including aging, female sex, obesity, T2DM, and high blood pressure.Moreover, the study highlights the potential benefits of specific diabetes drugs for heart failure treatment. In the HFpEF mouse model, experiments were conducted to evaluate the efficacy of various potential therapeutics targeting the improvement of the cardiometabolic status, such as SGLT2 inhibitors and GLP-1 receptor agonists. These drugs exhibited promise in enhancing heart health in the preclinical HFpEF model, particularly the GLP-1 receptor agonists.In summary, this thesis suggests an improved approach to studying HFpEF through mouse models that better mimic the human condition. By gaining a deeper understanding of the roles played by age, sex, and other associated health issues in HFpEF, the aim is to enhance the translational value of preclinical HFpEF research

Translation of heart failure with preserved ejection fraction: a tale of mice and men

Heart failure with preserved ejection fraction (HFpEF) represents a significant health concern with limited treatment options. This thesis addresses the challenges associated with developing pre-clinical models for HFpEF and delves into exploring the underlying disease mechanisms. The thesis proposes a comprehensive translational research approach aimed at enhancing the understanding of HFpEF and expediting the development of novel treatment strategies.Initially, the thesis proposes guidelines for designing HFpEF mouse models intended to more accurately mimic HFpEF in humans. These models take into account factors such as age, sex, and comorbidities often associated with HFpEF, such as obesity and type 2 diabetes mellitus (T2DM). Subsequently, the thesis describes the successful development of a new mouse model that closely resembles the HFpEF observed in humans. This model incorporates multiple factors including aging, female sex, obesity, T2DM, and high blood pressure.Moreover, the study highlights the potential benefits of specific diabetes drugs for heart failure treatment. In the HFpEF mouse model, experiments were conducted to evaluate the efficacy of various potential therapeutics targeting the improvement of the cardiometabolic status, such as SGLT2 inhibitors and GLP-1 receptor agonists. These drugs exhibited promise in enhancing heart health in the preclinical HFpEF model, particularly the GLP-1 receptor agonists.In summary, this thesis suggests an improved approach to studying HFpEF through mouse models that better mimic the human condition. By gaining a deeper understanding of the roles played by age, sex, and other associated health issues in HFpEF, the aim is to enhance the translational value of preclinical HFpEF research

Analyzing the precision of JSW measurements using 3D scans and statistical models

One of the methods to diagnose rheumatoid arthritis (RA) is measuring joint space narrowing over time. A method is presented to analyze the sensitivity of this measurement to positioning of the hand. Micro-CT scans are used to generate projections of a joint under varying angles of rotation. A semi-automatic method is used to measure the joint space width (JSW) for each projection. A Statistical model is used to investigate whether the rotation can be detected from a 2D radiograph. It is shown that rotation of the hand has a significant influence on the measured JSW

Translation of heart failure with preserved ejection fraction: a tale of mice and men

Heart failure with preserved ejection fraction (HFpEF) represents a significant health concern with limited treatment options. This thesis addresses the challenges associated with developing pre-clinical models for HFpEF and delves into exploring the underlying disease mechanisms. The thesis proposes a comprehensive translational research approach aimed at enhancing the understanding of HFpEF and expediting the development of novel treatment strategies.Initially, the thesis proposes guidelines for designing HFpEF mouse models intended to more accurately mimic HFpEF in humans. These models take into account factors such as age, sex, and comorbidities often associated with HFpEF, such as obesity and type 2 diabetes mellitus (T2DM). Subsequently, the thesis describes the successful development of a new mouse model that closely resembles the HFpEF observed in humans. This model incorporates multiple factors including aging, female sex, obesity, T2DM, and high blood pressure.Moreover, the study highlights the potential benefits of specific diabetes drugs for heart failure treatment. In the HFpEF mouse model, experiments were conducted to evaluate the efficacy of various potential therapeutics targeting the improvement of the cardiometabolic status, such as SGLT2 inhibitors and GLP-1 receptor agonists. These drugs exhibited promise in enhancing heart health in the preclinical HFpEF model, particularly the GLP-1 receptor agonists.In summary, this thesis suggests an improved approach to studying HFpEF through mouse models that better mimic the human condition. By gaining a deeper understanding of the roles played by age, sex, and other associated health issues in HFpEF, the aim is to enhance the translational value of preclinical HFpEF research

The influence of voluntary upper body exercise on the performance of stimulated paralysed human quadriceps

In this study the influence of voluntary upper body exercise on the performance of stimulated paralysed human quadriceps was investigated in five subjects with spinal cord lesions in the thoracic spine. The experimental setup consisted of computer-controlled stimulation of the quadriceps using electrodes on the surface of the skin, a dynamometer for isometric or isokinetic loading of the lower leg, and a rowing ergometer for upper body exercise. In all subjects, quadriceps fatigue tests were conducted to study the influence of upper body exercise on knee torque during sustained continuous or intermittent stimulation of quadriceps. The relative asymptotic torque appeared to be significantly higher with the presence of upper body exercise than without. This was consistently found both between trials (starting with or without upper body exercise) as well as within trials, when upper body exercise was started or stopped during the trial. No significant influence of upper body exercise on the time constant of initial torque decline was found