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Hemodynamic Effects of Anthrax Toxins in the Rabbit Model and the Cardiac Pathology Induced by Lethal Toxin
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston/TX 77555, USA
Animal Resources Center, University of Texas Medical Branch, Galveston/TX 77555, USA
Department of Veterinary Sciences, University of Texas MD Anderson Cancer Center, Bastrop/ TX 78602, USA
Institute of Human Infections, University of Texas Medical Branch, Galveston/TX 77555, USA
* Author to whom correspondence should be addressed.
Received: 30 April 2011; in revised form: 11 June 2011 / Accepted: 21 June 2011 / Published: 23 June 2011
Abstract: Anthrax lethal toxin (LeTx) and edema toxin (EdTx) have been shown to alter hemodynamics in the rodent model, while LeTx primarily is reported to induce extensive tissue pathology. However, the rodent model has limitations when used for comparison to higher organisms such as humans. The rabbit model, on the other hand, has gained recognition as a useful model for studying anthrax infection and its pathophysiological effects. In this study, we assessed the hemodynamic effects of lethal toxin (LeTx) and edema toxin (EdTx) in the rabbit model using physiologically relevant amounts of the toxins. Moreover, we further examine the pathological effects of LeTx on cardiac tissue. We intravenously injected Dutch-belted rabbits with either low-dose and high-dose recombinant LeTx or a single dose of EdTx. The animals’ heart rate and mean arterial pressure were continuously monitored via telemetry until either 48 or 72 h post-challenge. Additional animals challenged with LeTx were used for cardiac troponin I (cTnI) quantitation, cardiac histopathology, and echocardiography. LeTx depressed heart rate at the lower dose and mean arterial pressure (MAP) at the higher dose. EdTx, on the other hand, temporarily intensified heart rate while lowering MAP. Both doses of LeTx caused cardiac pathology with the higher dose having a more profound effect. Lastly, left-ventricular dilation due to LeTx was not apparent at the given time-points. Our study demonstrates the hemodynamic effects of anthrax toxins, as well as the pathological effects of LeTx on the heart in the rabbit model, and it provides further evidence for the toxins’ direct impact on the heart.
Keywords: anthrax; lethal toxin; rabbit model; cardiac
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Lawrence, W.S.; Marshall, J.R.; Zavala, D.L.; Weaver, L.E.; Baze, W.B.; Moen, S.T.; Whorton, E.B.; Gourley, R.L.; Peterson, J.W. Hemodynamic Effects of Anthrax Toxins in the Rabbit Model and the Cardiac Pathology Induced by Lethal Toxin. Toxins 2011, 3, 721-736.
Lawrence WS, Marshall JR, Zavala DL, Weaver LE, Baze WB, Moen ST, Whorton EB, Gourley RL, Peterson JW. Hemodynamic Effects of Anthrax Toxins in the Rabbit Model and the Cardiac Pathology Induced by Lethal Toxin. Toxins. 2011; 3(6):721-736.
Lawrence, William S.; Marshall, Jeffrey R.; Zavala, Diana L.; Weaver, Lori E.; Baze, Wallace B.; Moen, Scott T.; Whorton, Elbert B.; Gourley, Randy L.; Peterson, Johnny W. 2011. "Hemodynamic Effects of Anthrax Toxins in the Rabbit Model and the Cardiac Pathology Induced by Lethal Toxin." Toxins 3, no. 6: 721-736.