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The characteristics of the left ventricle of the human heart considered as a pump have been extensively analysed. Using a new approach relying heavily on the Tensor Calculus, a theoretical model describing the mechanical and dynamical operation of the left ventricle has been developed. This has considerably greater versatility than previously proposed models. In particular the physiological shape, both under normal as well as many abnormal situations, is realistically simulated. Further, the mechanical behaviour of the ventricular wall is synthesised from anatomical data concerning the cardiac muscle fibre structure of the wall. Its mechanical and dynamical properties are then, as in the physiological situation, dependent on those of the muscle fibre. These fibre properties have also been fully investigated and a simple new model for cardiac muscle dynamics, incorporating active state, proposed. This description of the ventricular behaviour in terms of muscle properties represents the first logically structured link between cardiac muscle fibre characteristics and ventricular performance.

Thesis (doctoral)--Universitetet i Göteborg.

Thesis (doctoral)--Universitetet i Göteborg.

No description available.

Clinically, the modified Bruce protocol is widely used to predict functional capacity in cardiac patients. However, it has been suggested that cardiac patients have lower oxygen uptakes for standard workloads. In order to study this, we measured oxygen uptake (V02) and venous bloodV02 derived from lactic acid concentration during a modified Bruce treadmill protocol in 12 pest myocardial infarction (MI) and 12 normal males. During three stages of the protocol mean oxygen uptake was significantly lower (1.42 - 6.2 ml/kg.min; p < .001) for the pest MI than the normal males.However, venous blood lactic acid concentrations were not different at these stages. The MI patients' measured V02 for three stages of the protocol ranged from 1.8 - 7.3 ml/kg.min lower than the Bruce predictions for cardiacs. In addition, measured V02 (max) for cardiac patients were from 3.68 to 11.15 ml/kg.min lower than the predicted the normal subjects. These data suggest myocardial damage may slow oxygen kinetics and results in lower actual V02during treadmill testing. However, blood lactic acid concentrations failed to demonstrate an anaerobic compensation for the lower V02 in pest MI patients.

Thesis (M.S.)--University of Wisconsin--Madison, 1984. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 12-13).

Cardiovascular disease (CVD) is a major cause of mortality and morbidity worldwide, often with heart failure as the terminal stage. Clinical studies have associated elevated levels of trimethylamine N-oxide (TMAO), a gut-derived metabolite, with adverse outcomes of CVD. As of today, TMAO's effects on cardiac structure and function are not well understood. In this study, both male and female TMAO-treated hearts showed functional deficits based on electrocardiography and echocardiography results. Immunohistochemistry results showed signs of hypertrophic cardiomyopathy in TMAO-treated male hearts while female TMAO-treated hearts showed signs of dilated cardiomyopathy. Neither TMAO group showed signs of fibrosis. Overproduction of reactive oxygen species was only observed in male TMAO-treated hearts. At the level of individual cardiomyocytes, significant delays in time to reach maximum contraction and dilation were only seen in TMAO-treated male hearts along with higher contractile force. Overall, TMAO-treated hearts show significant functional deficits with altered structure in a sex-specific way. Our study utilizes a variety of methods to comprehensively characterize features of TMAO-induced heart failure in both males and females which extends our current knowledge from human clinical associations. / Master of Science / Cardiovascular disease (CVD) is a major cause of mortality and morbidity worldwide, often with heart failure as the terminal stage. Clinical studies have associated elevated levels of trimethylamine N-oxide (TMAO), a compound derived from eggs, red meat and seafood, with adverse outcomes of CVD. As of today, TMAO's impact on the heart is not well understood. After supplementing mice with TMAO, we discovered deficiencies in heart function coupled with altered heart structure showing signs of hypertrophic cardiomyopathy in males and dilated cardiomyopathy in females. In-depth experiments suggest that TMAO-induced cell stress could be a potential underlying cause of previously mentioned changes but the specific mechanisms require further investigation. Overall, TMAO-treated hearts show significant functional deficits with altered structure in a sex-specific way. Our study utilizes a variety of methods to characterize features of TMAO-induced heart failure aiming to unravel relevant biological changes in both male and female mice which extends our knowledge from human clinical associations.

Cardiovascular disease, often induced by hypertension, represents a serious health threat, is a primary cause of death worldwide, and results in altered cardiovascular function and ECM composition. Hypertension and related cardiovascular diseases are associated with immune dysfunction. This dissertation investigated the role of T-lymphocytes in modulating cardiovascular function and ECM composition as a possible therapeutic for the treatment of cardiovascular disease. Study one investigated the role of TCR peptide in the development of hypertension and subsequent cardiovascular changes in Balb/C mice. The coadminstration of TCR and L-NAME/8% NaCl reduced the effects of L-NAME/8% NaCl, decreasing blood pressure and crosslinked collagen compared to L-NAME/8% NaCl alone. Study two examined the effects of T-lymphocyte function on cardiovascular structure and function. Adoptive transfer of T-lymphocytes from C57BL/6 WT mice into C57BL/6 SCID mice induced changes in the SCID so that it resembled the WT donor, with increased percent crosslinked collagen and LOX activity. Hemodynamics in the SCID recipient resembled that of the WT and were significantly different from the sham injected SCID. Study three combined aspects of both previous studies. T-lymphocytes were adoptively transferred from hypertensive WT donors into naïve SCID recipients, who developed hypertension and cardiovascular function resembling the hypertensive donor, as well as changes in the ECM, including increased collagen crosslinking. Study four investigated the effect of strain specific T-lymphocyte polarization on hypertension induced cardiac ECM remodeling. Balb/C, C57BL/6 WT, and C57BL/6 SCID had divergent responses to L-NAME induced hypertension. Ventricular stiffness increased in Balb/C, decreased in C57 SCID and did not change in C57 WT; LOX activity changed correspondingly in all groups. The final study examined the effect of TCR administration on LOX activity and collagen crosslinking. Th1 polarization increased LOX activity and crosslinked collagen with corresponding changes in cardiovascular function. In conclusion, modulation of T-lymphocyte function alters cardiovascular function and ECM composition in pathologic and non-pathologic conditions. Immune modulation should be further investigated as a therapeutic for cardiovascular disease.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused, in most cases, by the complete absence of the 427 kD cytoskeletal protein, dystrophin. Without dystrophin, the dystrophin-associated protein complex (DAPC) does not form and the plasma membrane is destabilised. There is no effective treatment and affected individuals die from respiratory failure and cardiomyopathy by age 30. This thesis describes experiments in which in vivo cardiac function was measured using non-invasive magnetic resonance imaging in a number of mouse models relevant to muscular dystrophy. As syncoilin forms a link from the DAPC to the cytoskeleton, it was postulated in Chapter 3 that the syncoilin knockout mouse would have cardiac defects similar to those caused by the loss of dystrophin. However, the loss of syncoilin did not alter the protein levels of its binding partners, measured by western blotting, and caused no defect in heart function or structure, measured using histological staining. Similarly, in Chapter 4, a mouse with a mutation in the transient receptor potential channel canonical type 3 (TRPC3), a receptor/stretch-activated cation channel thought to be involved in the pathogenesis of DMD, was found to have no functional or morphological cardiac defect. In the mdx mouse, a mouse model of DMD that lacks dystrophin, cardiomyopathy was prevented by either increasing levels of the dystrophin related protein, utrophin, or of dystrophin, in the diaphragm, which thereby restored diaphragm function. In Chapter 5 it was found that in a transgenic mdx mouse in which utrophin was over-expressed in skeletal muscle and diaphragm, but not in the heart, cardiac function was restored to wild-type levels. However, histologically the transgenic heart showed more fibrosis and immune cell infiltration than that of untreated mdx controls. In Chapter 6 it was found that in mdx mice treated with a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO), that resulted in high dystrophin restoration in skeletal muscle and diaphragm only, cardiac function was also restored to wild-type levels. In Chapter 6 it was also found that in dystrophin/utrophin-deficient double-knockout (dKO) mice, a more severely affected animal model of DMD, treatment with a PPMO again produced high levels of dystrophin only in skeletal muscle and diaphragm, and once more restored cardiac function to wild-type levels. In the dKO mouse, there was no difference in heart function between treatment of the diaphragm plus the heart and treatment of the diaphragm alone. Restoration of diaphragm and other respiratory muscle function, irrespective of the method used, was sufficient to prevent cardiomyopathy in dystrophic mice. The novel mechanism of treating respiratory muscles to prevent cardiomyopathy in dystrophic mice has implications for the study of heart function in the current DMD mouse models and suggests a new approach to treatment.