The candidate for the Mentored Clinical Scientist Development Award was awarded the MD degree from the University of Wisconsin and completed a residency in Anesthesiology at the University of Iowa and a research fellowship at the Medical College of Wisconsin. During fellowship training the candidate investigated the actions of anesthetics on coronary vascular reactivity in chronically-instrumented dogs. The proposed award will enable the candidate to accomplish the following objectives: 1) develop a broadly based foundation of scientific knowledge and research techniques; 2) define the mechanisms of cardioprotective actions of volatile anesthetics in post-ischemic, reperfused myocardium: and 3) allow the candidate to independently plan and conduct basic research. The research development plan will facilitate the candidate's accomplishment of these objectives by providing opportunities for advance education in molecular and cellular biology and cardiovascular physiology in a rich and varied academic research environment. The candidate will be directed in her efforts by an interdisciplinary group of investigators in cardiology, physiology, pharmacology and anesthesiology. Opportunities will be available for the candidate to present and discuss research in progress with other young investigators in several productive, well-equipped laboratories. Within this environment, the candidate will investigate the actions of the volatile anesthetics, isoflurane and halothane, to modulate cardioprotective signal transduction. The role of adenosine triphosphate-regulated potassium (KATP) channels, adenosine receptors and protein kinase C activation by volatile anesthetics to enhance functional recovery of stunned myocardium and to mimic ischemic preconditioning will be examined in acutely-instrumented dogs. Additional studies will be performed to evaluate the actions of these anesthetics on whole cell KATP currents and to investigate the interactions of ischemia and anesthetics on G protein expression in myocardium. This award will provide a foundation for the development of the candidate as an independent investigator, and the results will ultimately contribute to improvement in the perioperative care of patients with cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003690-05
Application #
6388408
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (F1))
Program Officer
Commarato, Michael
Project Start
1997-07-01
Project End
2002-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
5
Fiscal Year
2001
Total Cost
$116,640
Indirect Cost
Name
Medical College of Wisconsin
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
LaDisa Jr, John F; Olson, Lars E; Hettrick, Douglas A et al. (2005) Axial stent strut angle influences wall shear stress after stent implantation: analysis using 3D computational fluid dynamics models of stent foreshortening. Biomed Eng Online 4:59
LaDisa Jr, John F; Olson, Lars E; Molthen, Robert C et al. (2005) Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries. Am J Physiol Heart Circ Physiol 288:H2465-75
LaDisa Jr, John F; Olson, Lars E; Guler, Ismail et al. (2005) Circumferential vascular deformation after stent implantation alters wall shear stress evaluated with time-dependent 3D computational fluid dynamics models. J Appl Physiol 98:947-57
LaDisa Jr, John F; Meier, Heidi T; Olson, Lars E et al. (2005) Antegrade iliac artery stent implantation for the temporal and spatial examination of stent-induced neointimal hyperplasia and alterations in regional fluid dynamics. J Pharmacol Toxicol Methods 51:115-21
Ladisa Jr, John F; Olson, Lars E; Ropella, Kristina M et al. (2005) Microfocal X-ray computed tomography post-processing operations for optimizing reconstruction volumes of stented arteries during 3D computational fluid dynamics modeling. Comput Methods Programs Biomed 79:121-34
Tanaka, Katsuya; Ludwig, Lynda M; Kersten, Judy R et al. (2004) Mechanisms of cardioprotection by volatile anesthetics. Anesthesiology 100:707-21
Ludwig, Lynda M; Tanaka, Katsuya; Eells, Janis T et al. (2004) Preconditioning by isoflurane is mediated by reactive oxygen species generated from mitochondrial electron transport chain complex III. Anesth Analg 99:1308-15; table of contents
Weihrauch, Dorothee; Lohr, Nicole L; Mraovic, Boris et al. (2004) Chronic hyperglycemia attenuates coronary collateral development and impairs proliferative properties of myocardial interstitial fluid by production of angiostatin. Circulation 109:2343-8
LaDisa Jr, John F; Olson, Lars E; Guler, Ismail et al. (2004) Stent design properties and deployment ratio influence indexes of wall shear stress: a three-dimensional computational fluid dynamics investigation within a normal artery. J Appl Physiol 97:424-30; discussion 416
Pagel, Paul S; Kehl, Franz; Gare, Meir et al. (2003) Mechanical function of the left atrium: new insights based on analysis of pressure-volume relations and Doppler echocardiography. Anesthesiology 98:975-94

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