The overall objective of this application is to support the principal investigator's development in a career focused on patient-oriented research. To accomplish this objective, the proposed program has both training and scientific components. The training component will include specific course work and instruction in biostatistics, clinical epidemiology, research methodology, and trial design. The scientific component of the proposed award will be in the field of neurocardiology, with a focus on cardiac dysfunction after subarachnoid hemorrhage (SAH). Many cardiac abnormalities have been reported after SAH. including electrocardiographic changes, arrhythmia, and left ventricular systolic dysfunction. Though many aspects of this syndrome remain unexplained, the most important issues are its undefined pathophysiology, reversibility, and therapy. The scientific program will test the following hypotheses: 2. Left (LV) and right (RV) ventricular systolic dysfunction occurring after SAH are reversible and independent of changes in myocardial perfusion and afterload. 3. Cause of donor brain death (SAH vs. others) and the presence of donor LV dysfunction are predictive of early recipient mortality after cardiac transplantation. A prospective cohort design will be used to determine the incidence and reversibility of RV and LV dysfunction after SAH, using serial echocardiographic measurements. In a substudy of patients with LV ejection fraction <40%, radionuclide imaging with technetium sestabmibi (MIBI) and meta[123]iodobenzylguanidine (MIBG) will be performed in order to determine the incidence of perfusion versus innervation abnormalities and their correlation with regional wall motion abnormalities of the left ventricle. In order to determine whether the observed contractile abnormalities are independent of changes in afterload, the LV end-systolic wall stress / end-systolic volume relationship will be determined in each substudy subject. A secondary analysis of the United Network for Organ Sharing (UNOS) and California Transplant Donor Network databases will be performed in order to determine the effects of donor cause of death and LV dysfunction on early recipient mortality rates.
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