Dr. Prabhu
Sumanth D. Prabhu, M.D.
Professor of Medicine, and Physiology and Biophysics
University Scholar
Director, U of L Heart Failure
Tel.: (502) 852-7959*/sec. 1839;
E-mail: sprabhu@louisville.edu
Dr. Prabhu is a heart failure cardiologist and clinician-scientist. He is Director of the U of L Heart Failure Section and Medical Director of Heart Failure at U of L Hospital. Research in the Prabhu laboratory focuses on the mechanisms of pathological ventricular remodeling in heart failure. One central theme is inflammation and oxidative stress in the failing heart. Our work in rodent models has demonstrated that chronic β-adrenergic receptor activation induces inflammatory cytokines in the heart, and that amelioration of inflammation plays an important role in the therapeutic benefits of β-blockade in heart failure. More recently, we have shown that tumor necrosis factor (TNF) has divergent receptor-specific effects in the failing heart, such that signaling via TNF receptor-1 exacerbates hypertrophy, inflammation, and apoptosis, whereas signaling via TNF receptor-2 ameliorates these events. We have also extended this theme in a different direction, having shown that environmental exposure to aldehyde pollutants induces cardiac dysfunction, chronic inflammation, TNF expression and cardiomyopathy, raising the concept of an environmental basis for idiopathic dilated cardiomyopathy.
Clinically, Dr. Prabhu attends to patients with end-stage heart failure, often requiring left ventricular assist devices (LVADs) or cardiac transplantation. Along with Cardiothoracic Surgery (Dr. Slaughter) and Biomedical Engineering (Dr. Koenig), the Prabhu lab is examining the myocardial and systemic effects of biomechanical support with the goal of uncovering potential mechanisms of myocardial recovery. To this end, we have developed a biorepository of blood, tissue and sophisticated hemodynamic data prior to and after LVAD support that is being used for translational studies. Also in development is a large animal (bovine) model of ischemic heart failure that will be ultimately used to test different modes of mechanical support (and adjunctive therapy) and their effects on myocardial recovery. Translational studies are planned to move fundamental mechanisms to the clinical setting.
Dr. Prabhu is a member of the American Society for Clinical Investigation and a regular member of the NIH CCHF Study Section. His research is currently funded by the NIH and the VA, and he is the past recipient of an Established Investigator Grant from the American Heart Association. He is a member of the Editorial Board of Circulation Research.
Recent Publications:
1. Hamid T, Gu Y, Ortines R, Bhattacharya C, Wang GW, Xuan YT, Prabhu SD. Divergent TNF receptor-related remodeling responses in heart failure: role of NF-kB and inflammatory activation. Circulation. 2009;119:1386-97.
2. Venkatachalam K, Prabhu SD, Reddy VS, Boylston WH, Valente AJ, Chandrasekar B. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury. J Biol Chem. 2009;284:7853-65.
3. Slaughter MS, Bartoli CR, Sobieski MA, Pantalos GM, Giridharan GA, Dowling RD, Prabhu SD, Farrar DJ, Koenig SC. Intraoperative evaluation of the HeartMate II flow estimator. J Heart Lung Transplant. 2009 Jan;28(1):39-43.
4. Koenig SC, Giridharan GA, Ewert D, Schroeder M, Ionan C, Slaughter MS, Sobieski MA Pantalos GM, Dowling RD, Prabhu SD. Human, bovine and porcine systemic vascular input impedance are not equivalent: Implications for device testing and xenotransplantion in heart failure. J Heart Lung Transplant. 2008;27:1340-1347.
5. Koenig SC, Litwak KN, Giridharan GA, Pantalos GM, Dowling RD, Prabhu SD, Slaughter MS, Sobieski MA, Spence PA. Acute hemodynamic efficacy and histopathology of a 32-ml subcutaneous counterpulsation device in a calf model of diminished cardiac function. ASAIO J. 2008;54:578-584.
6. West MB, Rokosh G, Obal D, Velayutham M, Xuan Y-T, Hill BG, Keith R, Schrader J, Guo Y, Conklin DJ, Prabhu SD, Zweier JL, Bolli R, Bhatnagar A. Cardiac myocyte-specific expression of inducible nitric oxide synthase protects against ischemia/reperfusion injury by preventing mitochondrial permeability transition. Circulation. 2008;118:1970-1978.
7. Chandrasekar B, Boylston WH, Venkatachalam K, Webster NJG, Prabhu SD, Valente AJ. Adiponectin blocks interleukin-18-mediated endothelial cell death via APPL1-dependent AMPK activation and IKK/NF-kB/PTEN suppression. J Biol Chem. 2008;283:24889-98.
8. Zhou G, Li X, Hein DW, Xiang X, Marshall JP, Prabhu SD*, Cai L*. Metallothionein suppresses angiotensin II-induced NADPH oxidase activation, nitrosative stress, apoptosis, and pathological remodeling in the heart. J Am Coll Cardiol. 2008;52:655-66. *Equal author contribution.
9. Soukhova-O’Hare GK, Ortines RV, Gu Y, Nozdrachev AD, Prabhu SD, Gozal D. Reactive oxygen species and L-Ca2+ channels are involved in the cardiovascular effects following postnatal intermittent hypoxia in adult SHR rats. Hypertension. 2008;52:156-162.
10. Wang GW, Guo Y, Vondriska TM, Zhang J, Zhang S, Tsai LL, Zong NC, Bolli R, Bhatnagar A, Prabhu SD. Acrolein consumption exacerbates myocardial ischemic injury and blocks nitric oxide-induced PKCe signaling and cardioprotection. J Mol Cell Cardiol. 2008;44:1016-1022.
11. Venkatachalam K, Mummidi S, Cortez DM, Prabhu SD, Valente AJ, Chandrasekar B. Resveratrol inhibits high glucose-induced PI3K/AKT/ERK-dependent interleukin-17 expression in primary mouse cardiac fibroblasts. Am J Physiol Heart Circ Physiol. 2008; 294: H2078-H2087.
12. Majdalany D, Prabhu S, Makaryus AN. A true emergency? Am J Med. 2008;121:290-292.
13. Song Y, Du Y, Prabhu SD, Epstein PN. Diabetic cardiomyopathy in OVE26 mice shows mitochondrial ROS production and divergence between in vivo and in vitro contractility. Rev Diabet Stud. 2007;4:159-68.
14. Luo J, Hill BG, Gu Y, Cai J, Srivastava S, Bhatnagar A, Prabhu SD. Mechanisms of acrolein-induced myocardial dysfunction: Implications for environmental and endogenous aldehyde exposure. Am J Physiol Heart Circ Physiol. 2007;293:H3673–H3684.
15. Prabhu SD. Altered left ventricular-arterial coupling precedes pump dysfunction in early heart failure. Heart and Vessels. 2007;22:170-177.
16. Srivastava S, Chandrasekar B, Gu Y, Luo J, Hamid T, Hill BG, Prabhu SD. Downregulation of CuZn-superoxide dismutase contributes to b-adrenergic receptor-mediated oxidative stress in the heart. Cardiovasc Res. 2007;74:445-455.
17. Travis A, Giridharan GA, Pantalos GM, Dowling RD, Prabhu SD, Slaughter M, Sobieski M, Undar A, Koenig SC. Vascular pulsatility in clinical patients with a pulsatile or continuous flow ventricular assist device. J Thorac Cardiovasc Surg. 2007;133:517-52
