Research Forum Abstracts
19 A Swine Model for Poison-Induced Cardiac Arrest Using
Intravenous Potassium Cyanide
Bebarta VS, Little C, Fragoso M, Heard K/Department of Emergency Medicine,
Wilford Hall Medical Center, San Antonio, TX; Division of Emergency Medicine,
University of Colorado Health Sciences Center, Denver, CO; Department of
Surgery, University of Colorado Health Sciences Center, Denver, CO; Rocky
Mountain Poison and Drug Center-Denver Health, Denver, CO
Study Objectives: Animal models have been used for cardiovascular toxicity in
poisoning; however, there are no reported models of poison-induced cardiac arrest
(CA). Models for other types of cardiac arrest exist (ventricular fibrillation, asphyxia,
and exsanguination). A reproducible model is required to evaluate the efficacy of
antidotes in low-flow states. Our study objective was to create an animal model that
1) reproducibly generates poison-induced cardiac arrest and 2) allows for recovery
with appropriate treatment.
Methods: In our grant-funded study, adult female Sus scrofa swine were
endotracheally intubated and anesthetized. One venous and two arterial Millar
catheters were placed to administer medications, withdraw samples, and obtain
continuous hemodynamics. The pigs were then allowed to stabilize for 15 minutes
prior to obtaining baseline hemodynamic and metabolic measurements. Intravenous
potassium cyanide (KCN), safer and more reproducible than inhalation, was infused
at 0.5 mg/kg/min. This rate, titrated with a goal of achieving cardiac arrest (MAP 30
mmHg and pulse wave amplitude ⬍ 10 mmHg), was met between 10 to 15 min after
starting the infusion. Once CA occurred, cardiopulmonary resuscitation (CPR) was
initiated with a mechanical chest compressor at 100 compressions/min. Mechanical
ventilation was ceased upon initiation of the KCN infusion, and restarted at ROSC
(systolic blood pressure [MAP] ⬎ 50 mm Hg and a pulse pressure ⬎ 20 for 1
minute). Animals were then treated with epinephrine (n⫽2), hydroxocobalamin
(n⫽2) or sodium nitrite/sodium thiosulfate (n⫽1).
Results: The median dose of cyanide required to produce CA was 3 mg/kg (range
2-5 mg/kg). Median time from initiation of infusion to CA was 9 min (range 4 to 19
min). All animals had ROSC within 4 minutes of treatment and survived for 2 hours
after arrest.
Conclusion: With this grant-funded preliminary study, we developed a swine
model for poison-induced CA. We used intravenous KCN as the poisoning agent, a
chemical that can induce severe toxicity quickly, but allows animals to recover with
treatment. This model can be used for future comparative studies.
EMF-1 Thioredoxin Nitration by Peroxynitrite:
Contribution to Cardiomyocyte Apoptosis
Lau WB/Thomas Jefferson University Hospital, Philadelphia, PA
Study Objectives: Growing evidence from both animal experiments and clinical
observations indicates that myocardial infarction post myocardial
ischemia/reperfusion (MI/R), a most significant cause of death in the United States, is
caused not only by necrosis but also apoptosis. Mechanisms leading to post-ischemic
apoptosis remain incompletely understood. Evidence exists that ROS plays a causative
role in MI/R injury, and that thioredoxin (Trx) is a potent anti-oxidant molecule.
However, whether nitrative modification of Trx may alter its anti-oxidant and anti-
apoptotic activity has never been investigated. Our hypothesis in this grant is that
nitration of Trx plays a causative role in myocardial apoptosis signaling.
Methods: Viable cardiomyocytes were cultured per protocol from 2-3 month old
male C57B16/J mice, with 72 hour survival. Cardiomyocytes were treated for 3 hours
with 50 ␮M SIN-1, an agent that simultaneously releases nitric oxide (NO) and
superoxide (O2-) to generate peroxynitrite (ONOO-), either in the presence or
absence of rhTrx (500nM). Cardiomyocyte apoptosis was assessed via histological
(TUNEL) and biochemical (caspase 3 activation) methods. Data were analyzed by
ANOVA.
Results: Cardiomyocyte exposure to the ONOO- donor SIN-1 resulted in
significant apoptosis evidenced by increased TUNEL staining and caspase 3
activation. Treatment with rhTrx significantly attenuated SIN-1 induced apoptosis
(figures demonstrate TUNEL staining apoptosis index % and caspase 3 activity).
Conclusions: Trx attenuated SIN-1-induced apoptosis, indicating Trx is capable
of blocking nitrative stress-induced apoptosis. Nitrated Trx does not exert the same
cardiomyocyte-protective apoptotic effect. Trx protein nitration inhibition may be a
novel therapeutic strategy to reduce myocardial reperfusion injury.
Volume , .  : September 
20 CT Coronary Angiography During Initial Visit Decreases
Rate of Return Visits Relative To Standard Care
Chang A, Litt H, Shofer FS, McCusker C, Baxt WG, Hollander JE/University of
Pennsylvania, Philadelphia, PA
Study Objective: For low risk chest pain patients, cardiac catheterization but not
noninvasive stress testing decreases repeat ED visits and hospital admissions. The
impact of coronary CTA (CCTA) on re-hospitalization is unknown. We examined 30
day re-hospitalization rates in low risk chest pain patients (TIMI score, 0-2) that had
negative CTA or negative standard evaluation on index visit.
Methods:
Study Design: Observational nonrandomized cohort study. Setting: university
hospital ED.
Protocol: Low risk patients without acute ischemia on electrocardiogram (ECG)
who had negative CCTA were compared to “control” patients who had negative
evaluations prior to hospital release (stress test or “rule out” since these groups have
previously been shown to have same readmission rate). Data included demographics,
medical history, ECG, cardiac markers. Main outcome was 30-day rehospitalization.
Data presented as % frequency occurrence with 95% CI’s.
Results: There were 799 patients enrolled (mean age, 49.3 years; 42% male; 68%
Black). After exclusion of the 33 patients with positive tests, 766 remained in study
group: 253 with CCTA; and 513 controls (patients with and without stress test were
combined since outcomes were similar and prior studies show similar rates of
rehospitalization). Compared to controls, CCTA patients were younger (46 v 51),
but otherwise similar (39 v 42% male, 68 v 70% black, 1.2 v 1.4 cardiac risk factors).
There were 4 deaths: none in the CCTA group. No patient had a nonfatal myocardial
infarction within 30 days. With respect to our main outcome patients with CCTA
had a 2% rehospitalization rate (95% CI, 0.7-4.8%) and control patients had a 6.5%
rehospitalization rate (95% CI, 4.6-9.0%); difference, 4.5% (95% confidence interval
for the difference, 1.4-7.3%; p⫽0.007).
Conclusions: A negative CCTA during index visit decreases the 30 day
rehospitalization rate more than standard of care including a negative stress test. This
may offer an advantage for the management of ED and observation unit patients.
21 Efficacy and Safety of Vernakalant Hydrochloride
Injection (RSD1235) for the Conversion of Acute Atrial
Fibrillation in Patients Presenting to the Emergency
Department Within 48 Hours of Onset
Stiell I, Roy D, Pratt C, Dickinson G, Mangal B/University of Ottawa, Ottawa, ON,
Canada; University of Montréal, Montréal, PQ, Canada; The Methodist DeBakey
Heart Center, Houston, TX; Cardiome Pharma Corp., Vancouver, BC, Canada
Study Objectives: Vernakalant hydrochloride injection is a novel atrial selective,
frequency-dependent Na⫹ and early-activating K⫹ channel blocker for the treatment
of atrial fibrillation (AF), the most common sustained arrhythmia. Reported here is a
subanalysis in patients with acute AF (lasting 3 to 48 h) from the placebo-controlled
Atrial Fibrillation Conversion Trial (ACT I), which assessed the efficacy and safety of
vernakalant in converting AF lasting 3 h to ⬍45 d to sinus rhythm (SR).
Methods: Patients with AF were randomly assigned in a 2:1 ratio to vernakalant 3
mg/kg or placebo infused over 10 min. After 15 min, a second 10-min infusion of
vernakalant 2 mg/kg or placebo was given if AF persisted or atrial flutter was present.
The primary efficacy measure was the percentage of patients demonstrating
conversion to SR for at least 1 min within 90 min of dosing (responders). Other
efficacy measures included median time to conversion and the percentage of patients
still in SR at hour 24 and day 7. This analysis includes 103 patients with acute AF
given vernakalant and 61 given placebo.
Results: The average age in the vernakalant and placebo groups was 59 years, and
71% and 69% of each group, respectively, were men. A significantly higher
percentage of patients with acute AF given vernakalant (62.1%) than of those given
placebo (5.0%) demonstrated conversion to SR within 90 min (P⬍.0001).
Conversion from AF to SR with vernakalant was rapid and sustained; among
responders taking vernakalant, 78% required only 1 dose, median conversion time
was 11 min, and SR was maintained for 24 h in 97% and for 7 days in 93%.
Vernakalant was well tolerated: the most common adverse events (AEs) in patients
given vernakalant were taste disturbance (32.0%), sneezing (16.5%), and nausea
(15.5%). The incidence of serious AEs was similar in the vernakalant (11.7%) and
placebo (14.8%) treatment groups.
Conclusion: In patients with acute AF, vernakalant produced a rapid and
Annals of Emergency Medicine S7