Date of Award
Doctor of Philosophy
The cardiovascular, pulmonary and musculoskeletal systems were investigated in seven studies of patients with end-stage heart failure before and/or after receiving a heart transplant. The purposes of the studies were to determine the time course and magnitude of the changes in peak oxygen uptake, cardiopulmonary response to exercise and peripheral skeletal muscle histology and biochemistry after cardiac transplantation. In addition, the physiological basis for the limited exercise capacity and the effect of exercise posture on cardiac performance and secretion of atrial natriuretic peptide was also evaluated in cardiac transplant patients.;In the first study, the peak oxygen uptake almost doubled from the pre-transplant values in the first three months following transplantation. The increased exercise capacity was associated with improved blood pressure, heart rate and ventilatory responses to exercise. In the second study, lung volumes, but not diffusing capacity, improved in the first year after cardiac transplantation. In the third study, increased skeletal muscle fibre cross sectional area and glycolytic and oxidative enzyme activities were observed in the first year post transplantation using skeletal muscle biopsy of the vastus lateralis.;In the fourth study, the low peak oxygen uptake, as a percent of predicted, in patients after cardiac transplantation appears to be due to some peripheral limitations.;In the fifth study, the marked increase in cardiac filling pressure during supine exercise was associated with a lower slope of the cardiac output-oxygen uptake relationship when compared to the upright position. In the sixth study, higher cardiac filling pressures at peak supine exercise were associated with higher plasma ANP levels when compared to exercise in the upright posture. In the final study, two patients with mitochondrial myopathy who underwent cardiac transplantation demonstrated the typical hyperkinetic circulatory response to exercise despite cardiac denervation.;The present results show that exercise capacity improves markedly early after cardiac transplantation. The improved exercise capacity is associated with changes in lung function and peripheral skeletal muscle adaptations in the first year after transplantation. The exercise capacity however is still low at one or more years following transplantation (2/3 of predicted) possibly due to peripheral limitations.