[Frontiers in Bioscience 12, 4670-4675, May 1, 2007]

Lethal and edema toxins of anthrax induce distinct hemodynamic dysfunction

Linley E. Watson1, Jonathan Mock2, Hind Lal3, Guangrong Lu3, Raymond W. Bourdeau4, Wei-Jen Tang4, Stephen H. Leppla5, David E. Dostal3, Arthur E. Frankel6

1Division of Cardiology, Scott and White Memorial Hospital, Scott, Sherwood and Brindley Foundation and Cardiovascular Research Institute, Division of Molecular Cardiology, Texas A and M University System, Health Science Center College of Medicine, Temple, TX, 2Division of Cardiology, Scott and White Memorial Hospital, Scott, Sherwood and Brindley Foundation, 3Cardiovascular Research Institute, Division of Molecular Cardiology, Texas A and M University System, Health Science Center College of Medicine, Temple, TX, 4Ben May Department for Cancer Research, The University of Chicago, Chicago, IL, 5Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infections Diseases, Bethesda, MD, 6Scott and White Cancer Research Institute, Temple, TX

FIGURES

Figure 1. Example of modified Simpson rule tracings at baseline compared to 12 h after injection in LeTx injected rat. End diastolic area increased from 0.67 cm2 to 0.88 cm2, end systolic area increased from 0.29 cm2 to 0.59 cm2, and ejection fraction decreased from 77 to 45 percent.

Figure 2. Box plots at 18 hours post LeTx injection compared to controls of ejection fraction and systolic blood pressure. The box represents the middle 50% of the data. The line through the box represents the median. The lines (whiskers) extending from the box represent the upper and lower 25% of the data. The line on each plot connects the means of the sample. The end-systolic pressure-volume point has been shifted to the right and downward. SYS_BP = systolic blood pressure. CNTL=Controls (n=8). LeTx= Anthrax Lethal Toxin injected (n=13). p= 0.035. p=0.034

Figure 3. Paired t test of baseline to 18-hour echocardiograms of controls and LeTx injected. = not significant. P-Value=0.00047. P-Value = 0.002. P-Value = 0.006. P-Value = 0.002. See Legend Figure 2 for Box plot symbols. LVAs = left ventricular end systolic area. Vcfc = heart-rate-corrected-velocity of circumferential fiber shortening. Vp = color m-mode velocity of propagation.

Figure 4. EdTx 12 hours post injection resulted in decreased left ventricular end diastolic (LVAd) and end systolic areas (LVAs).

Figure 5. EdTx 12 hours post injection reduced cardiac output (CO) without reducing heart rate (HR).

Figure 6. EdTx 12 hours post injection reduces both systolic and diastolic pulmonary vein Doppler velocities.