Terry Vanden Hoek, M.D.

Genomic Responses to Oxidant Stress During Cellular and Whole Body Ischemia/Reperfusion

Research Summary

Current research is focused on the genomic changes associated with sudden death resuscitation. Sudden death refers to diseases of sudden shock (Usually due to cardiac arrest or severe traumatic hemorrhage) that result in a rapid transition from life to death within minutes-despite full human function preceding the event and often despite initially successful resuscitation and intensive care. To better understand the determinants of post-resuscitation outcome, we are using murine models of cardiac arrest and hemorragic shock to characterize genomic expression patterns associated with whole body ischemia/reperfusion. Gene expression patterns that are common to multiple organs and most associated with microcirculatory injury and cardiovascular collapse are currently being investigated. Cardiomyocyte and endothelial cell models of ischemia/reperfusion are being used to further study the cell biology of implicated proteins, particularly their relationship to oxidant signaling events and critical stress response pathways. Our goal is to translate this work intothe clinical setting to further validate and test possible "molecular vital signs" that can guide resuscitation back to full human function.

Selected Papers

Shao ZH, Becker LB, Vanden Hoek TL, Schumacker PT, Li CQ, Zhao D, Wojcik K, Anderson T, Qin Y, Dey L, Yuan CS. (2003). Grape seed proanthocyanidin extract attenuates oxidant injury in cardiomyocytes. Pharmacol Res 47:463-469.

Nolan JP, Morley PT, Vanden Hoek TL, Hickey RW, ALS Task Force. (2003). Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Circulation 108:118-121.

Shao ZH, Vanden Hoek TL, Xie J, Wojcik K, Chan KC, Li CQ, Hamann K, Qin Y, Schumacker PT, Becker LB, Yuan CS. (2003). Grape seed proanthocyanidins induce pro-oxidant toxicity in cardiomyocytes. Cardiovasc Toxicol 3(4):331-339.

Shao ZH, Xie JT, Vanden Hoek TL, Mehendale S, Aung H, Li CQ, Qin Y, Schumacker PT, Becker LB, Yuan CS. (2004). Antioxidant effects of American ginseng berry extract in cardiomyocytes exposed to acute oxidant stress. Biochim Biophys Acta 1670(3):165-171.

Qin Y *, Vanden Hoek TL *, Wojcik K, Anderson T, Li C-Q, Shao ZH, Becker LB and Hamann KJ. (2004). Caspase-dependent cytochrome c release and cell death in chick cardiomyocytes following simulated ischemia-reperfusion. Am J Physiol (Heart Circ Physiol), 286(6):H2280-6.* Co-first authors

Abella BS, Zhao D, Alvarado J, Hamann KJ, Vanden Hoek TL and Becker, LB. (2004). Intra-arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model. Circulation, 109: 2786-2791.

Shao ZH, Vanden Hoek TL, Li CQ, Schumacker PT, Becker LB, Chan KC, Qin Y, Yin JJ, Yuan CS. (2004). Synergistic effect of Scutellaria baicalensis and grape seed proanthocyanidins on scavenging reactive oxygen species in vitro. Am J Chin Med 32(1):89-95.

Vanden Hoek TL; Kasza KE; Beiser DG; Abella BS; Franklin JE, Oras, JJ; Alvarado JP; Anderson T; Son H; Wardrip CL; Zhao D; Wang, H; Becker, LB:. (2004). Induced hypothermia by central venous infusion: Saline ice slurry versus chilled saline. Crit Care Med (suppl) 32 (9):425-431.

Abella BS, Alvarado JP, Myklebust H, Edelson D, Barry A, O’Hearn N, Vanden Hoek TL, and Becker LB: Deficiencies in multiple parameters of CPR quality during in-hospital cardiac arrest. JAMA, 293:305-310, 2005.
Abella BS, Sandbo N, Vassilatos P, Alvarado J, O’Hearn N, Wigder H, Hoffman P, CRT6, Tynus K, Vanden Hoek TL, Becker LB.  (2005). Chest compression rates during CPR are sub-optimal: A prospective study during in-hospital cardiac arrest. Circulation, 111(4): 428-434.

Abella BS, Rhee JW, Huang KN, Vanden Hoek TL, Becker LB.  (2005). Induced hypothermia is underutilized after resuscitation from cardiac arrest: A current practice survey. Resuscitation, 64:181-186.

Idris AH, Roberts J, Caruso L, Showstark M, Layon AJ, Becker LB, Vanden Hoek, TL, Gabrielli A. (2005). Oxidant Injury Occurs Rapidly after Cardiac Arrest, Cardiopulmonary Resuscitation (CPR), and Reperfusion. Crit Care Medicine, 33:2043-2048.