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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL004054-04
Application #
6638103
Study Section
Special Emphasis Panel (ZHL1-CSR-F (F1))
Program Officer
Commarato, Michael
Project Start
2000-05-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2003
Total Cost
$121,770
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Taub, Pam R; Fields, Jeremy D; Wu, Alan H B et al. (2011) Elevated BNP is associated with vasospasm-independent cerebral infarction following aneurysmal subarachnoid hemorrhage. Neurocrit Care 15:13-8
Zaroff, Jonathan G; Pawlikowska, Ludmila; Miss, Jacob C et al. (2006) Adrenoceptor polymorphisms and the risk of cardiac injury and dysfunction after subarachnoid hemorrhage. Stroke 37:1680-5
Fisher, Landis A; Ko, Nerissa; Miss, Jacob et al. (2006) Hypernatremia predicts adverse cardiovascular and neurological outcomes after SAH. Neurocrit Care 5:180-5
Banki, Nader; Kopelnik, Alexander; Tung, Poyee et al. (2006) Prospective analysis of prevalence, distribution, and rate of recovery of left ventricular systolic dysfunction in patients with subarachnoid hemorrhage. J Neurosurg 105:15-20
Yarlagadda, Sirisha; Rajendran, Pam; Miss, Jacob C et al. (2006) Cardiovascular predictors of in-patient mortality after subarachnoid hemorrhage. Neurocrit Care 5:102-7
Kothavale, Avinash; Banki, Nader M; Kopelnik, Alexander et al. (2006) Predictors of left ventricular regional wall motion abnormalities after subarachnoid hemorrhage. Neurocrit Care 4:199-205
Khush, Kiran; Kopelnik, Alexander; Tung, Poyee et al. (2005) Age and aneurysm position predict patterns of left ventricular dysfunction after subarachnoid hemorrhage. J Am Soc Echocardiogr 18:168-74
Tung, Poyee P; Olmsted, Elise; Kopelnik, Alexander et al. (2005) Plasma B-type natriuretic peptide levels are associated with early cardiac dysfunction after subarachnoid hemorrhage. Stroke 36:1567-9
Banki, Nader M; Kopelnik, Alexander; Dae, Michael W et al. (2005) Acute neurocardiogenic injury after subarachnoid hemorrhage. Circulation 112:3314-9
Kopelnik, Alexander; Fisher, Landis; Miss, Jacob C et al. (2005) Prevalence and implications of diastolic dysfunction after subarachnoid hemorrhage. Neurocrit Care 3:132-8

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