were treated sequentially with vehicle, Atenolol (ATN), Amrinone (AMR) and Itraconazole (ITZ) and effects compared to LVP indices. Echocardiography was performed in a darkened and quiet room. All examinations were performed by a board-certified veterinary cardiologist, using a GE Vivid i echocardiographic recorder. Two- dimensional, M-mode, spectral Doppler and color flow Doppler measurements were performed using a 3.5/6.9 MHz phased array sector transducer. Measurements were collected twice pre-study (day-5 and -2), pre-dose and once post-dose (2–3 h). Collected parameters included left ventricular internal dimensions, left ven- tricular posterior wall thickness, interventricular septum thickness, aortic diameter, ejection fraction (EF) and fractional shortening (FS). There were no changes following vehicle. The negative inotropes reduced EF and FS as expected (ATN -10% & -13%; ITZ: -23% & -29%). The same parameters increased following AMR treatment (+18% & +29%). These changes were similar to contractility changes observed in telemetry equipped dogs treated with the same compounds. Power analysis data was generated to illustrate the ability to detect changes in the collected parameters. In conclusion, echocardiography can be incorporated into toxicology study designs to provide a non-invasive assessment of cardiac function. doi:10.1016/j.vascn.2016.02.121 0123 A model of acute congestion with progressive induction of pulmonary edema in sheep with chronic ischemic left-ventricular dysfunction: Preliminary results Gail E. Geist a , Carlos del Rio a , Bradley Youngblood a , Kevin Render a , Yukie Ueyama a , Robert Hamlin a,b a QTest Labs, Columbus, OH, USA b The Ohio State University, Columbus, OH, USA An effectual, expeditious, and controlled method for the induction of pulmonary edema is a necessity for the evaluation of both therapies and monitoring-tools for congestive heart failure (HF); however, models of congestion, particularly in the setting of chronic HF are limited. In this study, pulmonary edema, as assessed by changes in extravascular lung water (EVLW), was induced and quantified in sheep with chronically-induced ischemic HF. Mixed-breed adult sheep (40–70 kg, n = 6) underwent serial coronary artery embolization procedures to trigger chronic left- ventricular dysfunction/remodeling consistent with HF. Subsequent- ly (~4 weeks later), sheep were anesthetized and instrumented for the monitoring of systemic/ventricular hemodynamics, cardiac/urine output, and EVLW via a dual-indicator (thermo-dilution) technique. Following instrumentation, acute congestion and subsequent pul- monary edema was induced with a combination of fluid (IV crystalloid, 0.5–1.0 L bolus, with 1.6–2.0 L/h infusion) and pressure (IV phenylephrine, 9–15 mg/h) overload; congestion was defined by clinically-elevated central venous (N 13 mmHg) and left-ventricular filling pressures (N 23 mmHg). Embolized sheep presented hemodynamic/mechanical indices consistent with HF. Overlapping overload triggered immediate and sustained elevations in intra-vascular lung volumes consistent with congestion, with all animals showing progressive increases in EVLW volumes. Pulmonary edema (defined as at least a 50% increase in EVLW) was reached (on average) 55 min after overload-induction (30–90 min); after 90 min the average increase in EVLW was 152% (50–197%). Taken together, these results indicate that a combination of pressure/volume overload is an effective means for the progressive induction of pulmonary edema secondary to acute congestion in sheep with existing left-ventricular dysfunction. doi:10.1016/j.vascn.2016.02.122 0124 Plasma miR-208: A robust early biomarker of cardiac drug induced injury in rats Stephanie Glineur, Pierrette de Ron, Etienne Hanon, Jean-Pierre Valentin, Sarah Dremier, Andre Nogueira da Costa UCB BioPharma SPRL, Braine L'Alleud, Belgium Drug-induced cardiac injury (DICI) detection is a major safety issue in drug development. While circulating microRNAs (miRs) have emerged as promising translational biomarkers, there is a critical need of novel early detection biomarkers of cardiotoxicity. This work aims at evaluating whether a panel of reported cardiac injury plasma miRs could serve as early DICI biomarkers in a 4-day rat preclinical model. Out of a panel of 68 selected targets, plasma miR-208a-3p was significantly upregulated after single administra- tion with either isoproterenol (ISO) or allylamine (AAM), providing the first evidence of miR-208a-3p detection after AAM exposure. Similarly to cardiac troponins (cTn), plasma miR-208a-3p release appears to be compound-specific with most significant early changes occurring in ISO-treated rats. Overall, miR-208a-3p performance in detecting the severity of myocardial injury is similar to that of cTn while the magnitude of miR-208a-3p and cTn increases in response to ISO and AAM administration is comparable. Our results highlight the importance of assessing the whole time-dependent profiles of miR expression. Hence, time course evaluation revealed plasma miR candidates whose expression was altered across the duration of the study in the vehicle group, restricting their utility as cardiac injury- specific biomarkers. In light of these findings, miR-208a-3p has a potential to complement the existing biomarkers of cardiac injury specifically in the context of evaluating toxicity in a time-dependent manner. Assessment of miR-208a-3p in other DICI settings would strengthen its credibility as an early detection biomarker leading to a warranted extensive and rigorous validation. doi:10.1016/j.vascn.2016.02.123 0125 Promising approach for the preclinical assessment of cardiac risks using left ventricular pressure–volume loop analyses in anesthetized monkeys Tomomichi Ishizaka, Yu Yoshimatsu, Yu Maeda, Wataru Takasaki, Katsuyoshi Chiba, Kazuhiko Mori Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan Load-independent cardiac parameters obtained from the ventricular pressure–volume relationship are recognized as gold standard indexes for evaluating cardiac inotropy and lusitropy. Such information using non-rodent species, which are widely used in in vivo safety pharmaco- logical studies, is still lacking. In this study, for better analyses of cardiac risks, load-independent and load-dependent pressure–volume loop parameters were assessed in addition to hemodynamic and electrocar- diographic changes in isoflurane-anesthetized monkeys. The animals were given milrinone (a PDE 3 inhibitor), metoprolol (a β-blocker), or dl-sotalol (a β +I Kr blocker) at two dose levels including clinically Abstracts 372