Table 2.
Summary of functional cardiac findings from preclinical studies in lethal toxin challenged models.
| Publication | Subjects | Route of Lethal Toxin Exposure | Functional Measurement | Findings |
|---|---|---|---|---|
| Watson et al. 2007 [13] | Sprague-Dawley rat | Intravenous bolus | Echocardiography | ▪20% increase in LVAs and LVAd within 2 h. Specific LVEF measurements not reported; ▪Increase in Vp |
| Watson et al. 2007 [52] | Sprague-Dawley rat | Intravenous bolus | Echocardiography | ▪30% reduction in LVEF in 11/14 rats surviving after 48 h related to acute increase in LVAs. No increase in LVAd noted; ▪Decreased VCFC, Decrease in Vp |
| Cheng et al. 2007 [57] | Canine | Intravenous bolus | Pressure-Volume catheter | ▪Significant LV dysfunction starting at 6 h with development of heart failure at 96 h; ▪Decreases in LVEF, stroke volume, LVESP, contractility, prolonged relaxation time constant, increases in LVEDP |
| Moayeri et al. 2009 [14] | C57BL/6J mouse | Intravenous bolus | Echocardiography | ▪Decreases in ejection fraction and fractional shortening at 24 h after LT challenge without change in stroke volume or CO |
| Sweeney et al. 2010 [17] | Purpose–bred Beagle | Continuous infusion | PA Catheter Echocardiography | ▪Low and high dose (see section 4) of LT caused progressive declines (15%–20%) in LVEF at 72 h; ▪No significant change in PAOP or SVI with either dose but CVP decreased with high dose |
| Lawrence et al. 2011 [20] | Dutch-belted rabbit | Intravenous bolus | Echocardiography | ▪Serial echo measurements at 0 to 48 h showed no significant change in LVAs or LVAd despite elevated markers of myocardial injury |
| Hicks et al. 2011 [59] | Isolated Sprague-Dawley rat heart | Continuous non-recirculating perfusion | Ex-vivo Langendorff Model | ▪No change in LVDP, RPP, or dP/dt max at a known lethal dose of LT; ▪A 10-fold increase in the lethal dose caused decreases in all measured parameters |
| Liu et al. 2013 [10] | Mouse | Intraperitoneal | Echocardiography | ▪Significant decrease in EF at 48 h after LT challenge |
| Golden et al. 2013 [16] | Sprague-Dawley rat | Intravenous bolus | Echocardiography | ▪Abnormal indices of diastolic dysfunction within 2–8 h including prolonged LV deceleration time, elevated E/E’ ratio, left atrial chamber enlargement and pulmonary regurgitation; ▪No change in EF noted |
| Li et al. 2015 [60] | Sprague-Dawley rat | Continuous infusion | Echocardiography in vivo followed by ex vivo Langendorff Model | ▪LT decreased CO and decreased LVEF at 8 and 48 h but increased it at 24 h measured with cardiac echo; ▪In isolated hearts following in vivo exposure to LT no consistent change at 8, 24, or 48 h in LVSP, LVDP, RPP, or dP/dt max or min |
CO: Cardiac output, dP/dt: Rate of change in LV pressure during contraction, LVDP: Left ventricular developed pressure (LVDP = LVSP − LVEDP), LVEDP: Left ventricular end diastolic pressure, LVEF: Left ventricular ejection fraction, LVESP: Left ventricular end systolic pressure, LVSP: Left ventricular systolic pressure, LVAs: Left ventricular area in systole, LVAd: Left ventricular area in diastole, PAOP: Pulmonary artery occlusion pressure, RPP: Rate pressure product (LVDP × HR), SVI: Stroke volume index, VCFC: velocity of circumferential fiber shortening, Vp: velocity of propagation.