Department of Surgery

Research

National Presentations

Linda Vona-Davis, Ph.D. presented a poster at the Thirtieth Annual Conference on Shock. Baltimore, Maryland June 9‑12, 2007

IN VIVO TACHYCARDIA AND THE ELEVATION OF INTRINSIC HEART RATE AFTER LPS TREATMENT.
P.D. Wearden* and L.C. Vona-Davis. Department of Surgery, West Virginia University, Morgantown, WV 26506

   Sepsis results in decreased contractility and tachycardia.  Other work has shown a loss of heart rate variability in sepsis, suggesting an elevation of the intrinsic heart rate (IHR). We hypothesized that an increase in the IHR contributes to the tachycardia observed following LPS treatment. Methods: Femoral catheters were placed in rats and blood pressure and heart rates (HR) were monitored for 16-20 hr after injection with LPS (5mg/kg). Autonomic blockade with atropine and propranolol provided an estimate of the IHR. Animals were dosed with hexamethonium after LPS to duplicate surgical excision of the heart. In a separate study, animals were depleted of catecholamines using reserpine prior to LPS. Animals were also pretreated with a b adrenoceptor antagonist (ßAR), bromo-acetyl alprenolol menthane (BAAM). Results: HR was 19% greater in LPS-treated animals with no significant changes in blood pressure. After both drugs, there was a 21% difference in IHR between groups. No changes in sympathetic and parasympathetic inputs were evident indicating that the difference in HR was due to changes in the IHR. Hexamethonium did not abolish the difference in HR confirming the observation. The depletion of catecholamines with reserpine attenuated the LPS-induced increase in IHR. Pretreatment with BAAM inhibited the increase in IHR indicating that the ßARis involved.

Linda Vona-Davis, PhD, will present at the 27th Annual Conference on Shock held in Halifax, Nova Scotia, June 10-13, 2004

LPS AND TNFa INDUCE SOCS-3 mRNA EXPRESSION IN CARDIAC MYOBLASTS.                          
L.Vona-Davis, K. Frankenberry*, K.Lebedeva*, D.W.McFadden*,West Virginia University, Dept. Surgery, Morgantown, WV 26506.

Suppressors of cytokine signaling (SOCS) proteins are important regulators of the immune system. Previous work in this laboratory showed an increase in SOCS-3 mRNA in pancreatic acinar cells in response to proinflammatory agents. SOCS-3 is normally expressed at low levels in the heart; however, the response to endotoxin (LPS) or inflammation (TNF- a) is unknown. We hypothesized that TNF- a and LPS would induce SOCS-3 mRNA expression in a cardiac progenitor cell line. Methods: Rat cardiac myoblasts (H9c2) received either LPS (10mg/ml) or TNF- a (10ng/ml) for 1, 3, 6, 8, 12 and 24 h. Total RNA was used in RT-PCR reactions for SOCS-3 mRNA expression. Values were standardized with 18S rRNA. Results: SOCS-3 mRNA expression was present in nonstimulated myoblasts. The response to TNF- a was biphasic as SOCS-3 expression was increased at early (within 1h) and late (24h) timepoints. Levels of SOCS-3 expression declined significantly (P < 0.05) from controls between 6-12h post treatment. The response to endotoxin was also biphasic, as SOCS-3 induction occurred early and late after a single dose. Conclusions: We have shown that LPS and TNF- a are potent activators of SOCS-3 expression in the heart. LPS or TNF- a -mediated SOCS-3 expression is one mechanism involved in the development of cardiac failure in sepsis.

As part of academic enrichment, Kristina Lebedeva, a native of Morgantown, conducted undergraduate research in the Department of Surgery with funds from the Eberly College.  Lebedeva plans to apply to medical school at WVU following graduation.

Previous National Presentations

Michael Szwerc, Dale R. Riggs, Barbara J. Jackson, Krista Frankenberry, Linda Vona-Davis, Cynthia Cunningham and David W. McFadden. MAPK and PI3-kinase inhibition reduces proliferation of Barrett’s adenocarcinoma in vitro. Presented at the 38th Annual Meeting of the Association for Academic Surgery, Houston, TX, November 11-13, 2004.

Linda Vona-Davis PhD, Z Xiaocheng, MD, A Yu, MD, D McFadden, MD, FACS. Modulation Of IL-6 In Cardiac Myoblasts During Endotoxemia.   36th Annual Meeting of the Association for Academic Surgery, November 7, 2002, Boston MA.  Abstract P61.

Ganga Prabahakar MD, Linda Vona-Davis PhD, David Murray PhD, Paresh Lakhani BS, Gordon Murray MD, FACS. Phosphocreatine Restores High-Energy Phosphates In Ischemic Myocardium:  Implication For Off-Pump Cardiac Revascularization.  88th Annual Clinical Congress, ACS, October 6, 2002, San Francisco, CA. S24

Vona-Davis, L., P.D. Wearden, N. H. Karne and R.C. Hill. Effect of creatine monohydrate on cardiac function in a rat model of endotoxemia.  The 34th Meeting of the Association for Academic Surgery, Tampa, FL, November 2000. Abstract

Vona-Davis, L., P. Wearden, D. Murray and R. Hill. High-energy phosphates and recovery of cardiac performance in endotoxic shock. 23rd Annual Conference on SHOCK, Snowbird, Utah, June 2000. Abstract 60.

Vona-Davis, L., P. Wearden, L. Millecchia, J. Hill, G. Timberlake and R. Hill.  Cardiac response to nitric oxide synthase inhibition using aminoquanidine in a rat model of endotoxemia.  Fourth International SHOCK Congress, Philadelphia, PA, June 1999. Abstract 176.