-
a S c i T e c h n o l j o u r n a lResearch Article
Johnson et al., Analg Resusc: Curr Res 2013,
S1http://dx.doi.org/10.4172/2324-903X.S1-002
International Publisher of Science, Technology and Medicine
Analgesia & Resuscitation : Current Research
All articles published in Analgesia & Resuscitation :
Current Research are the property of SciTechnol, and is protected
by copyright laws. Copyright © 2013, SciTechnol, All Rights
Reserved.
Effects of the ResQPod® on Maximum Concentration and Time to
Maximum Concentration of Epinephrine in a Porcine Cardiac Arrest
ModelDon Johnson1*, Jackie Rushton1, Maxwell Hernandez1, Jessica
Stone1, Jason Brzuchalski1, Libby Beck1, LTC Joseph O’Sullivan1 and
LTC Michael Loughren2
AbstractBackground: The ResQPod®, an impedance threshold device
(ITD), was developed to augment cardiac output during
cardiopulmonary resuscitation (CPR). If an ITD used with CPR does
in fact increase venous return and cardiac output, then the use of
such a device should increase the maximum concentration (Cmax) of
epinephrine in the plasma and decrease the time to maximum
concentration (Tmax). To our knowledge, no studies have
investigated the pharmacokinetics of epinephrine during CPR while
using the ResQPod®. The purpose of this study was to determine the
effect of the ResQPod® on plasma concentrations of epinephrine in
swine undergoing CPR for cardiac arrest.
Methods: This was a prospective, experimental, between-subjects
design. Twelve Yorkshire-cross swine were assigned one of two
groups: CPR with the ResQPod® and CPR without the use of the
ResQPod®. Pigs were administered potassium chloride by intravenous
(IV) route to achieve cardiac arrest. After two minutes of CPR,
epinephrine was administered by IV push. Blood samples were
collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 7.5 and 10 minutes
after the injection of epinephrine.
Results: Results are reported in means and standard deviations
respectively. Use of the ResQPod® resulted in lower Cmax than
control (219.34 ± 110.59 ng/mL; 471.53 ± 349.71 ng/mL). Tmax was
longer when using ResQPod® compared to the control group (4.75 ±
1.54 minutes; 3.42 ± 1.11 minutes). Although there were differences
between the groups, the results were not statistically significant
relative to Cmax and Tmax (p=0.276).
Conclusion: It appears the ResQPod® does not increase the
delivery of epinephrine during CPR. More research is needed to
evaluate the effects of the ResQPod® on epinephrine metabolite
levels and on survivability. If the ResQPod® boosts the circulation
of epinephrine to end organs, it is reasonable to predict that
epinephrine metabolite concentrations and survivability would be
higher than a control group.
KeywordsResQPod®; ITD; Epinephrine; CPR; Swine; Concentration;
Cardiac output; Cmax; Tmax
*Corresponding author: Don Johnson, US Army Graduate Program in
Anesthesia, Fort Sam Houston, 2619 Winding View, San Antonio, Texas
78260, USA, Tel: 210-714-4341; E-mail: [email protected]
Received: May 08, 2013 Accepted: May 24, 2013 Published: May 30,
2013
IntroductionCardiac arrest remains one of the leading causes of
mortality
with more than 900 occurrences daily in the United States alone
claiming an estimated 325,000 lives each year, 1,000 people a day
or one person every two minutes [1]. The ResQPod®, an impedance
threshold device (ITD), was developed to augment cardiac output
during cardiopulmonary resuscitation (CPR). The American Heart
Association (AHA) Guidelines 2005 for CPR and Emergency Cardiac
Care gave the ResQPod® a Class IIa recommendation [2]. The Class
IIa recommendation means the intervention has very good evidence to
support its use. Conversely, the 2010 AHA Guidelines state that it
was not possible to determine the relative contribution of an ITD
to the improved outcome. The use of an ITD may be considered by
trained personnel as a CPR adjunct in adult cardiac arrest [3].
The ResQPod® is placed between a self-inflating bag and mask or
endotracheal tube during manual ventilation. The ResQPod®
purportedly utilizes the interdependence of the respiratory and
circulatory systems and enhances venous return and cardiac output
during CPR by increasing the degree of negative intrathoracic
pressure. This effect is achieved by preventing the passive inflow
of air into the lungs during chest recoil between chest
compressions without impeding active ventilation [4].
The use of an ITD has been shown to improve coronary perfusion
pressure (CPP) anywhere from 30 to over 100% in multiple animal
studies [5-11]. In addition, the ITD has improved rates of return
to spontaneous circulation (ROSC) in both animal and human studies
[4,9,10,12-18]. Furthermore, the use of an ITD has shown improved
hospital discharge rates in multiple human studies [17,19].
The benefits of the ITD may be due to more than just its effects
on CPP. It is possible that the improved ROSC and hospital
discharge rates are also due to improved circulation of emergency
medications delivered during cardiac arrest. The 2010 AHA
guidelines state that 1 mg of epinephrine should be given after two
minutes of CPR and every 3-5 minutes thereafter. If the use of an
ITD during CPR does in fact increase venous return and cardiac
output, it stands to reason that the use of such a device would
improve the circulation of epinephrine in a cardiac arrest model.
To our knowledge, there are no studies that have examined the
pharmacokinetics of epinephrine given during CPR with an ITD. The
purpose of this study was to determine the effect of the ResQPod®
on plasma levels of epinephrine in swine undergoing CPR for cardiac
arrest.
MethodsThis study was a prospective, experimental between
subjects
design. The protocol was approved by the Institutional Animal
Care and Use Committee (IACUC), and the animals received care in
compliance with the Animal Welfare Act, the Guide for the Use of
Laboratory Animals. Twelve Yorkshire-cross swine weighing between
70-80 kg were equally assigned by the use of computer generated
numbers (n=6 per group) to one of two groups: CPR with the ResQPod®
and CPR without the use of the ResQPod®. To avoid any variability
in subjects, the investigators purchased the pigs from
-
Citation: Johnson D, Rushton J, Hernandez M, Stone J,
Brzuchalski J, et al. (2013) Effects of the ResQPod® on Maximum
Concentration and Time to Maximum Concentration of Epinephrine in a
Porcine Cardiac Arrest Model. Analg Resusc: Curr Res S1.
• Page 2 of 3 •
doi:http://dx.doi.org/10.4172/2324-903X.S1-002
In-hospital Cardiac Arrest
the same vendor, used pigs approximately the same size, and used
only male pigs. The rationale for using male pigs was to avoid any
potential hormonal effects. The swine were fed a standard diet and
observed for three days to ensure a good state of health; the
subjects where NPO after midnight the day before the
experiment.
Anesthesia was induced with an intramuscular injection of
Telazol (4-8 mg/kg) and inhaled isoflurane 4%-5%. After placement
of an endotracheal tube, the investigators reduced the isoflurane
concentration to a maintenance dose (0.5-2%) for the remainder of
the experiment. A peripheral IV was started on all subjects. Normal
saline (NS) was administered at keep vein open (KVO) rate to
maintain patency. The animals were ventilated at 8-10 ml/kg tidal
volume with a standard Narkomed anesthesia machine (Drager, Telfor,
Penn.) with an initial respiratory rate of 10-14 breaths per
minute. The swine were continuously monitored with the following
standard monitors: HR, BP, ECG, SpO2, ETCO2 and temperature. A
catheter for collection of blood specimens was inserted into the
left carotid artery using a cut-down technique. Potassium chloride
20 mg/kg was then administered via the IV and flushed with 10 ml of
normal saline. The electrocardiogram (EKG) tracing was observed for
any non-perfusing rhythm (ventricular fibrillation, pulseless
ventricular tachycardia, or asystole) indicating that the pig was
in cardiac arrest. Upon recognition of a non-perfusing rhythm, the
investigators discontinued anesthesia. The pig was allowed to stay
in arrest for two minutes.
After the two-minute period, CPR was initiated with a mechanical
CPR device, the “Thumper” (Michigan Instruments, Inc.). The
“Thumper” was used to automatically compress the sternum at a
predetermined depth of 1-1/2 inches at a rate of 100 beats per
minute according to the guidelines of the AHA. The Thumper was used
to ensure that the rate and depth of compression where consistent
over time and reproducible from animal to animal. The ResQPod®
group had the device placed on the endotracheal tube in accordance
with the manufacturer’s instructions.
Compressions with ventilations with 100% oxygen were continued
at a ratio of 30:2. After one minute of CPR, an initial baseline
blood specimen was collected from the arterial line followed by a
10 mL normal saline flush for all groups. One mg of epinephrine
diluted in 10 mL of normal saline was administered by IV push in
one second or less and followed by a 10 mL normal saline flush. In
addition to the baseline sample, blood samples (10 mL) were
collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 7.5 and 10 minutes after
the epinephrine injection. Before each sample was collected, 5 ml
of blood was discarded.
All plasma samples were sent to the University of Washington
Pharmacokinetics Laboratory, Seattle, Washington, for analysis. The
analysis of epinephrine in the plasma was performed by the high
performance liquid chromatography with mass spectrometry-mass
spectrometry (HPLC-MS/MS) as described by Zhang et al. [20].
Maximum plasma concentration (Cmax) and time to maximal
concentration (Tmax) were determined directly from the plasma
concentration-time data.
Statistical AnalysesA Multivariate Analyses of Variance (MANOVA)
was conducted
on pre-intervention data that included weight and vital signs.
In addition, a MANOVA was used to test for significance the
difference between the two groups (CPR with and without the
ResQPod®) on two response variables: Cmax and Tmax.
ResultsThe MANOVA indicated that there were no significant
differences
in the pre-interevention data (p > 0.05) indicating the
groups were equivalent on those parameters. The Cmax with the
ResQPod
® group was less compared to the group without the ResQPod®.
However, the Wilks Lamda, the test statistic for the MANOVA,
indicated there were no statistically significant differences
between the groups relative to either Cmax and or Tmax (p=0.276).
The results are summarized in Table 1.
DiscussionWe expected that the ResQPod® would enhance delivery
of
epinephrine to the central circulatory system during CPR.
Therefore, the ResQPod® would increase venous return and cardiac
output, which would decrease the time to maximum plasma
concentration of the circulating epinephrine. The effect of using
an ITD during CPR on Cmax is less predictable. On one hand, it
should enhance delivery of drug from the periphery more effectively
and increase plasma concentrations. However, enhanced cardiac
output would also increase distribution resulting in lower plasma
concentrations. In addition, it would increase liver blood flow,
thereby increasing metabolism resulting in lower plasma levels of
the parent drug. In future studies the impact of metabolism could
be determined by measuring plasma metabolite levels. However, in
the timeframe of this experiment (10 minutes), distribution would
be expected to have greater impact on plasma concentration than
metabolism.
The results of our study suggest that the use of the ResQPod®
during CPR does not enhance drug circulation and does not appear to
increase cardiac output. Although, numerous studies support
improved CPP and improved ROSC rates, there are studies that found
no improvement of CPP and have demonstrated a statistically
significant reduction in ROSC rates when using an ITD. Menegazzi et
al. offer a number of interesting explanations for their
observation that ROSC rates decreased when using the ITD to include
a theory that passive ventilation that normally occurs with chest
compression/relaxation is eliminated resulting in hypoventilation
[21]. When discussing the limitations of their study, they stated
that it was possible that the use of the “Thumper” did not allow
for complete chest recoil. Hence, this may have adversely affected
the functionality of the ITD. The present investigation also used a
“Thumper” and if this is true, it may have also adversely affected
the function of the ITD in our study. Nevertheless, the
manufacturers of both the Thumper and the ResQPod® do not specify
that these should not be used in combination.
In conclusion, this study compared the Cmax and Tmax of
Group Mean with Standard Deviation N
Cmax with ResQPod® 219.34 ± 110.59 ng/mL 6
Cmax without ResQPod® 471.53 ± 349.71 ng/mL 6
Tmax in minutes with ResQPod® 4.75 ± 1.54 6
Tmax in minutes without ResQPod® 3.42 ± 1.11 6
Cmax refers to the maximum concentration of the plasma
epinephrine; Tmax refers to the time to maximum concentration of
plasma epinephrine in minutes; Ng refers to nanograms and mL refers
to milliliters
Table 1: Result of Cmax and Tmax of Epinephrine.
-
Citation: Johnson D, Rushton J, Hernandez M, Stone J,
Brzuchalski J, et al. (2013) Effects of the ResQPod® on Maximum
Concentration and Time to Maximum Concentration of Epinephrine in a
Porcine Cardiac Arrest Model. Analg Resusc: Curr Res S1.
• Page 3 of 3 •
doi:http://dx.doi.org/10.4172/2324-903X.S1-002
In-hospital Cardiac Arrest
epinephrine in a cardiac arrest swine model using the ResQPod®
with CPR compared to CPR without the ResQPod®. A major limitation
of this study was that cardiac output was not measured. Future
research needs to be implemented investigating Cmax and Tmax in a
cardiac arrest model with the addition of monitoring cardiac
output. In addition, more research is needed to evaluate the
effects of the ResQPod® on survivability and serum epinephrine
metabolite levels. If the ResQPod® boosts the circulation of
epinephrine to end organs, it is reasonable to predict that
epinephrine metabolite concentrations and survivability will both
increase.References
1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, et
al. (2012) Executive summary: heart disease and stroke
statistics--2012 update: a report from the American Heart
Association. Circulation 125: 188-197.
2. ECC Committee, Subcommittees and Task Forces of the American
Heart Association (2005) American Heart Association Guidelines for
Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
Circulation 112: IV1-203.
3. Johnson D, Gegel B, Burgert J, Duncklee GW, Robison RR, et
al. (2010) Effects of the HEET garment in the prevention of
hypothermia in a porcine model. J Surg Res 164: 126-130.
4. Aufderheide TP, Nichol G, Rea TD, Brown SP, Leroux BG, et al.
(2011) A trial of an impedance threshold device in out-of-hospital
cardiac arrest. N Engl J Med 365: 798-806.
5. Lurie KG, Zielinski T, McKnite S, Aufderheide T, Voelckel W,
et al. (2012) Use of an inspiratory impedance valve improves
neurologically intact survival in a porcine model of ventricular
fibrillation. Circulation. 105: 124-129.
6. Buckley GJ, Shih A, Garcia-Pereira FL, Bandt C (2012) The
effect of using an impedance threshold device on hemodynamic
parameters during cardiopulmonary resuscitation in dogs. J Vet
Emerg Crit Care (San Antonio) 22: 435-440.
7. Lurie KG, Coffeen P, Shultz J, McKnite S, Detloff B, et al.
(1995) Improving active compression-decompression cardiopulmonary
resuscitation with an inspiratory impedance valve. Circulation 91:
1629-1632.
8. Lurie KG, Voelckel WG, Zielinski T, McKnite S, Lindstrom P,
et al. (2001) Improving standard cardiopulmonary resuscitation with
an inspiratory impedance threshold valve in a porcine model of
cardiac arrest. Anesth Analg 93: 649-655.
9. Raedler C, Voelckel WG, Wenzel V, Bahlmann L, Baumeier W, et
al. (2001) Vasopressor response in a porcine model of hypothermic
cardiac arrest is improved with active compression-decompression
cardiopulmonary resuscitation using the inspiratory impedance
threshold valve. 95: 1496-1502.
10. Srinivasan V, Nadkarni VM, Yannopoulos D, Marino BS,
Sigurdsson G, et al. (2006) Rapid induction of cerebral hypothermia
is enhanced with active compression-decompression plus inspiratory
impedance threshold device cardiopulmonary resusitation in a
porcine model of cardiac arrest. J Am Coll Cardiol 47: 835-841.
11. Yannopoulos D, Aufderheide TP (2007) Use of the Impedance
Threshold Device (ITD). Resuscitation 75: 193-194.
12. Lurie K, Zielinski T, McKnite S, Sukhum P (2000) Improving
the efficiency of cardiopulmonary resuscitation with an inspiratory
impedance threshold valve. Crit Care Med 28: N207-N209.
13. Lurie K, Voelckel W, Plaisance P, Zielinski T, McKnite S, et
al. (2000) Use of an inspiratory impedance threshold valve during
cardiopulmonary resuscitation: a progress report. Resuscitation 44:
219-230.
14. Plaisance P, Lurie KG, Payen D (2000) Inspiratory impedance
during active compression-decompression cardiopulmonary
resuscitation: a randomized evaluation in patients in cardiac
arrest. Circulation 101: 989-994.
15. Seekins MB, Reiss AJ (2011) Application of impedance
threshold devices during cardiopulmonary cerebral resuscitation. J
Vet Emerg Crit Care (San Antonio) 21: 187-192.
16. Segal N, Parquette B, Ziehr J, Yannopoulos D, Lindstrom D
(2013) Intrathoracic pressure regulation during cardiopulmonary
resuscitation: a feasibility case-series. Resuscitation 84:
450-453.
17. Aufderheide TP, Frascone RJ, Wayne MA, Mahoney BD, Swor RA,
et al. (2011) Standard cardiopulmonary resuscitation versus active
compression-decompression cardiopulmonary resuscitation with
augmentation of negative intrathoracic pressure for out-of-hospital
cardiac arrest: a randomised trial. Lancet 377: 301-311.
18. Wolcke BB, Mauer DK, Schoefmann MF, Teichmann H, Provo TA,
et al. (2003) Comparison of standard cardiopulmonary resuscitation
versus the combination of active compression-decompression
cardiopulmonary resuscitation and an inspiratory impedance
threshold device for out-of-hospital cardiac arrest. Circulation
108: 2201-2205.
19. Lurie KG, Yannopoulos D, McKnite SH, Herman ML, Idris AH, et
al. (2008) Comparison of a 10-breaths-per-minute versus a
2-breaths-per-minute strategy during cardiopulmonary resuscitation
in a porcine model of cardiac arrest. Respir Care 53: 862-870.
20. Zhang MY, Hughes ZA, Kerns EH, Lin Q, Beyer CE (2007)
Development of a liquid chromatography/tandem mass spectrometry
method for the quantitation of acetylcholine and related
neurotransmitters in brain microdialysis samples. J Pharm Biomed
Anal 44: 586-593.
21. Menegazzi JJ, Salcido DD, Menegazzi MT, Rittenberger JC,
Suffoletto BP, et al. (2007) Effects of an impedance threshold
device on hemodynamics and restoration of spontaneous circulation
in prolonged porcine ventricular fibrillation. Prehosp Emerg Care
11: 179-185.
Submit your next manuscript and get advantages of SciTechnol
submissions
50 Journals 21 Day rapid review process 1000 Editorial team 2
Million readers More than 5000 Publication immediately after
acceptance Quality and quick editorial, review processing
Submit your next manuscript at ●
www.scitechnol.com/submission
Author Affiliations Top1US Army Graduate Program in Anesthesia,
Fort Sam Houston, San Antonio, Texas, USA2Madigan Medical Center,
Seattle, Washington, USA
This article is published in the special issue, In-hospital
Cardiac Arrest and has been edited by Dr. Walid Trabelsi, Military
hospital of instruction of Tunis, Tunisia
http://www.ncbi.nlm.nih.gov/pubmed/22215894http://www.ncbi.nlm.nih.gov/pubmed/22215894http://www.ncbi.nlm.nih.gov/pubmed/22215894http://www.ncbi.nlm.nih.gov/pubmed/22215894http://www.ncbi.nlm.nih.gov/pubmed/16314375http://www.ncbi.nlm.nih.gov/pubmed/16314375http://www.ncbi.nlm.nih.gov/pubmed/16314375http://www.ncbi.nlm.nih.gov/pubmed/16314375http://www.ncbi.nlm.nih.gov/pubmed/16314375http://www.ncbi.nlm.nih.gov/pubmed/20060130http://www.ncbi.nlm.nih.gov/pubmed/20060130http://www.ncbi.nlm.nih.gov/pubmed/20060130http://www.ncbi.nlm.nih.gov/pubmed/20060130http://www.ncbi.nlm.nih.gov/pubmed/21879897http://www.ncbi.nlm.nih.gov/pubmed/21879897http://www.ncbi.nlm.nih.gov/pubmed/21879897http://www.ncbi.nlm.nih.gov/pubmed/21879897http://www.ncbi.nlm.nih.gov/pubmed/11772887http://www.ncbi.nlm.nih.gov/pubmed/11772887http://www.ncbi.nlm.nih.gov/pubmed/11772887http://www.ncbi.nlm.nih.gov/pubmed/11772887http://www.ncbi.nlm.nih.gov/pubmed/22805594http://www.ncbi.nlm.nih.gov/pubmed/22805594http://www.ncbi.nlm.nih.gov/pubmed/22805594http://www.ncbi.nlm.nih.gov/pubmed/22805594http://www.ncbi.nlm.nih.gov/pubmed/22805594http://www.ncbi.nlm.nih.gov/pubmed/7882467http://www.ncbi.nlm.nih.gov/pubmed/7882467http://www.ncbi.nlm.nih.gov/pubmed/7882467http://www.ncbi.nlm.nih.gov/pubmed/7882467http://www.ncbi.nlm.nih.gov/pubmed/11524335http://www.ncbi.nlm.nih.gov/pubmed/11524335http://www.ncbi.nlm.nih.gov/pubmed/11524335http://www.ncbi.nlm.nih.gov/pubmed/11524335http://www.ncbi.nlm.nih.gov/pubmed/11524335http://www.ncbi.nlm.nih.gov/pubmed/12456407http://www.ncbi.nlm.nih.gov/pubmed/12456407http://www.ncbi.nlm.nih.gov/pubmed/12456407http://www.ncbi.nlm.nih.gov/pubmed/12456407http://www.ncbi.nlm.nih.gov/pubmed/12456407http://www.ncbi.nlm.nih.gov/pubmed/12456407http://www.ncbi.nlm.nih.gov/pubmed/16487853http://www.ncbi.nlm.nih.gov/pubmed/16487853http://www.ncbi.nlm.nih.gov/pubmed/16487853http://www.ncbi.nlm.nih.gov/pubmed/16487853http://www.ncbi.nlm.nih.gov/pubmed/16487853http://www.ncbi.nlm.nih.gov/pubmed/16487853http://www.ncbi.nlm.nih.gov/pubmed/17574321http://www.ncbi.nlm.nih.gov/pubmed/17574321http://www.ncbi.nlm.nih.gov/pubmed/17574321http://www.ncbi.nlm.nih.gov/pubmed/11098948http://www.ncbi.nlm.nih.gov/pubmed/11098948http://www.ncbi.nlm.nih.gov/pubmed/11098948http://www.ncbi.nlm.nih.gov/pubmed/11098948http://www.ncbi.nlm.nih.gov/pubmed/10825624http://www.ncbi.nlm.nih.gov/pubmed/10825624http://www.ncbi.nlm.nih.gov/pubmed/10825624http://www.ncbi.nlm.nih.gov/pubmed/10825624http://www.ncbi.nlm.nih.gov/pubmed/10704165http://www.ncbi.nlm.nih.gov/pubmed/10704165http://www.ncbi.nlm.nih.gov/pubmed/10704165http://www.ncbi.nlm.nih.gov/pubmed/10704165http://www.ncbi.nlm.nih.gov/pubmed/21631704http://www.ncbi.nlm.nih.gov/pubmed/21631704http://www.ncbi.nlm.nih.gov/pubmed/21631704http://www.ncbi.nlm.nih.gov/pubmed/21631704http://www.ncbi.nlm.nih.gov/pubmed/22902465http://www.ncbi.nlm.nih.gov/pubmed/22902465http://www.ncbi.nlm.nih.gov/pubmed/22902465http://www.ncbi.nlm.nih.gov/pubmed/22902465http://www.ncbi.nlm.nih.gov/pubmed/21251705http://www.ncbi.nlm.nih.gov/pubmed/21251705http://www.ncbi.nlm.nih.gov/pubmed/21251705http://www.ncbi.nlm.nih.gov/pubmed/21251705http://www.ncbi.nlm.nih.gov/pubmed/21251705http://www.ncbi.nlm.nih.gov/pubmed/21251705http://www.ncbi.nlm.nih.gov/pubmed/14568898http://www.ncbi.nlm.nih.gov/pubmed/14568898http://www.ncbi.nlm.nih.gov/pubmed/14568898http://www.ncbi.nlm.nih.gov/pubmed/14568898http://www.ncbi.nlm.nih.gov/pubmed/14568898http://www.ncbi.nlm.nih.gov/pubmed/14568898http://www.ncbi.nlm.nih.gov/pubmed/17383138http://www.ncbi.nlm.nih.gov/pubmed/17383138http://www.ncbi.nlm.nih.gov/pubmed/17383138http://www.ncbi.nlm.nih.gov/pubmed/17383138http://www.ncbi.nlm.nih.gov/pubmed/17383138http://www.ncbi.nlm.nih.gov/pubmed/17454804http://www.ncbi.nlm.nih.gov/pubmed/17454804http://www.ncbi.nlm.nih.gov/pubmed/17454804http://www.ncbi.nlm.nih.gov/pubmed/17454804
TitleCorresponding
authorAbstractKeywordsIntroductionMethodsStatistical Analyses
ResultsDiscussionReferencesTable 1
