Loading...
Please wait, while we are loading the content...
Similar Documents
Protective Antigen Antibody Augments Hemodynamic Support in Anthrax Lethal Toxin Shock in Canines
| Content Provider | Paperity |
|---|---|
| Author | Sun, Junfeng Subramanian, G. Mani Migone, Thi-sau Li, Yan Barochia, Amisha V. Solomon, Steven B. Eichacker, Peter Q. Cui, Xizhong Bolmer, Sally D. |
| Abstract | Background. Anthrax-associated shock is closely linked to lethal toxin (LT) release and is highly lethal despite conventional hemodynamic support. We investigated whether protective antigen–directed monoclonal antibody (PA-mAb) treatment further augments titrated hemodynamic support. Methods and Results. Forty sedated, mechanically ventilated, instrumented canines challenged with anthrax LT were assigned to no treatment (controls), hemodynamic support alone (protocol-titrated fluids and norepinephrine), PA-mAb alone (administered at start of LT infusion [0 hours] or 9 or 12 hours later), or both, and observed for 96 hours. Although all 8 controls died, 2 of 8 animals receiving hemodynamic support alone survived (median survival times 65 vs 85 hours, respectively; P = .03). PA-mAb alone at 0 hour improved survival (5 of 5 animals survived), but efficacy decreased progressively with delayed treatment (9 hours, 2 of 3 survived; 12 hours, 0 of 4 survived) (P = .004 comparing survival across treatment times). However, combined treatment increased survival irrespective of PA-mAb administration time (0 hours, 4 of 5 animals; 9 hours, 3 of 3 animals; and 12 hours, 4 of 5 animals survived) (P = .95 comparing treatment times). Compared to hemodynamic support alone, when combined over PA-mAb treatment times (0, 9, and 12 hours), combination therapy produced higher survival (P = .008), central venous pressures, and left ventricular ejection fractions, and lower heart rates, norepinephrine requirements and fluid retention (P ≤ .03). Conclusions. PA-mAb may augment conventional hemodynamic support during anthrax LT-associated shock. |
| Starting Page | 818 |
| Ending Page | 829 |
| File Format | HTM / HTML |
| ISSN | 00221899 |
| DOI | 10.1093/infdis/jir834 |
| Issue Number | 5 |
| Journal | Journal of Infectious Diseases |
| Volume Number | 205 |
| e-ISSN | 15376613 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2012-03-01 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Immunology and Allergy |
