scholarly journals Pharmacokinetics of the Hypoxia-Imaging Agent [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress

2017 ◽  
Author(s):  
Daria Stypinski ◽  
Stephen A. McQuarrie ◽  
Alexander J.B. McEwan ◽  
Leonard I. Wiebe
Keyword(s):  
Healthy Volunteers ◽  
Venous Blood ◽  
Volume Of Distribution ◽  
Total Radioactivity ◽  
Whole Body ◽  
Strenuous Exercise ◽  
Published Data ◽  
Cardiac Stress ◽  
Myocardial Hypoxia ◽  
Total Body

Objective:  To determine the pharmacokinetics (PK) and detect changes in cardiac uptake of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in healthy volunteers after exercise-based cardiac stress, to establish a rational basis for studies of focal myocardial hypoxia in cardiac patients using [123I]IAZA.  Method:  Three healthy male volunteers ran the ‘Bruce’ treadmill protocol (criterion heart rate is 85 % of [220 – age]).  Approximately one minute before reaching this level, [123I]IAZA (4.0 mCi/0.85 mg) was administered as a slow (1-3 min) single bolus i.v. injection, then the volunteer continued running for an additional 1 min.  Serum from venous blood samples, taken at pre-determined intervals from 1 min to 45 h, was analyzed by radioHPLC.  PK parameters were derived for [123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses (NCA).  Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing.  PK data and scintigraphic images were compared to published data from healthy volunteers administered [123I]IAZA at rest.  Results:  Following strenuous exercise, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t1/2β of 195 and 290 min, respectively].  Total body clearance (CLTB) and steady state volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[123I].  The t1/2β, CLTB and Vss values were comparable to those reported previously for rested volunteers.  The t1/2α was approximately 4-fold shorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested subjects.  The heart was visualized in early whole body scintigraphic images, but overall there were no apparent differences from images reported for rested volunteers.  Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed muscle.  Conclusion:  The PK and whole-body scintigrams for [123I]IAZA in exercise-stressed healthy volunteers showed no clinically relevant differences relative to non-exercised volunteers.  [123I]IAZA may therefore be suitable for the detection of viable, hypoxic myocardium in areas of myocardial perfusion deficiency.

scholarly journals Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress

2018 ◽  
Author(s):  
Daria Stypinski ◽  
Stephen A McQuarrie ◽  
Alexander JB McEwan ◽  
Leonard I Wiebe
Keyword(s):  
Healthy Volunteers ◽  
Stress Test ◽  
Venous Catheter ◽  
Potential Effect ◽  
Exercise Stress ◽  
Whole Body ◽  
Serum Samples ◽  
Cardiac Stress ◽  
Myocardial Hypoxia ◽  
The Impact

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [123I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male volunteers ran the ‘Bruce’ treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The ‘Bruce’ criterion heart rate is 85% of [220 – age]. Approximately one minute before reaching this level, [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1–3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [123I]IAZA data from healthy volunteers rest. Following exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t1/2β of 195 and 290 min, respectively]. Total body clearance (CLTB) and the steady state volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The t1/2β, CLTB and Vss values were comparable to those reported previously for rested volunteers. The t1/2α was approximately 4-fold shorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [123I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [123I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [123I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

scholarly journals Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers

2011 ◽  
Vol 55 (6) ◽  
pp. 2927-2936 ◽  
Author(s):  
J. B. Bulitta ◽  
M. Kinzig ◽  
C. B. Landersdorfer ◽  
U. Holzgrabe ◽  
U. Stephan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Volunteers ◽  
High Performance ◽  
Standard Dose ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Nonparametric Bootstrap ◽  
Population Pk ◽  
Total Body ◽  
Similar Body

ABSTRACTCystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma and urine concentrations were determined by high-performance liquid chromatography (HPLC). Population PK and Monte Carlo simulations were performed using NONMEM and S-ADAPT and a duration of an unbound plasma concentration above the MIC ≥ 65% of the dosing interval as a pharmacodynamic target. Unscaled clearances for CF patients were similar to those seen with healthy volunteers, and the volume of distribution was 6% lower for CF patients. Linear scaling of total clearance by WT resulted in clearance that was 20% higher (P≤ 0.001 [nonparametric bootstrap]) in CF patients. Allometric scaling by LBM explained the differences between the two subject groups with respect to average clearance and volume of distribution and reduced the unexplained between-subject variability of renal and nonrenal clearance by 10 to 14%. For the CF patients, robust (>90%) probabilities of target attainment (PTA) were achieved by the administration of a standard dose of 2 g/70 kg WT every 12 h (Q12h) given as 30-min infusions for MICs ≤ 1.5 mg/liter. As alternative dosage regimens, a 5-h infusion of 1.33 g/70 kg WT Q8h achieved robust PTAs for MICs ≤ 8 to 12 mg/liter and a continuous infusion of 4 g/day for MICs ≤ 12 mg/liter. Prolonged infusion of cefpirome is expected to be superior to short-term infusions for MICs between 2 and 12 mg/liter.

Pharmacokinetics and Arteriovenous Differences in Clevidipine Concentration following a Short- and a Long-term Intravenous Infusion in Healthy Volunteers

2000 ◽  
Vol 92 (4) ◽  
pp. 993-1001 ◽  
Author(s):  
Hans Ericsson ◽  
Ulf Bredberg ◽  
Ulf Eriksson ◽  
Åse Jolin-Mellgård ◽  
Margareta Nordlander ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Healthy Volunteers ◽  
Venous Blood ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Blood Levels ◽  
Blood Concentrations ◽  
Arterial Blood ◽  
The Mean

Background Clevidipine is an ultra-short-acting calcium antagonist developed for reduction and control of blood pressure during cardiac surgery. The objectives of the current study were to determine the pharmacokinetics of clevidipine after 20-min and 24-h intravenous infusions, and to determine the relation between the arterial and venous concentrations and the hemodynamic responses to clevidipine in healthy volunteers. Methods Four volunteers received clevidipine for 20 min, and eight subjects were administered clevidipine intravenously for 24 h at two different dose rates. Arterial and venous blood samples were drawn for pharmacokinetic evaluation, and blood pressure and heart rate were recorded. Results A triexponential disposition model described the pharmacokinetics of clevidipine. The mean arterial blood clearance of clevidipine was 0.069l/kg-1/min-1 and the mean volume of distribution at steady state was 0.19 l/kg. The duration of the infusion had negligible effect on the pharmacokinetic parameters, and the context-sensitive half-time for clevidipine, simulated from the mean pharmacokinetic parameters derived after 24 h infusion at the highest dose, was less than 1 min. The arterial blood levels reached steady state within 2 min of the start of infusion and were about twice as high as those in the venous blood at steady state. The peak response preceded the peak venous concentration and was slightly delayed from the peak arterial blood concentration. Conclusion Clevidipine is a high clearance drug with a small volume of distribution, resulting in extremely short half-lives in healthy subjects. The initial rapid increase in the arterial blood concentrations and the short equilibrium time between the blood and the biophase suggest that clevidipine can be rapidly titrated to the desired effect.

scholarly journals Dynamic Changes of Heart Failure Biomarkers in Response to Parabolic Flight

2020 ◽  
Vol 21 (10) ◽  
pp. 3467
Author(s):  
Peter Jirak ◽  
Bernhard Wernly ◽  
Michael Lichtenauer ◽  
Vera Paar ◽  
Marcus Franz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Healthy Volunteers ◽  
Calcium Homeostasis ◽  
Parabolic Flight ◽  
Venous Blood ◽  
Short Term ◽  
Dynamic Changes ◽  
Fetuin A ◽  
Cardiac Stress ◽  
Time Points

Background: we aimed at investigating the influence of weightlessness and hypergravity by means of parabolic flight on the levels of the heart failure biomarkers H-FABP, sST2, IL-33, GDF-15, suPAR and Fetuin-A. Methods: 14 healthy volunteers (males: eight; mean age: 28.9) undergoing 31 short-term phases of weightlessness and hypergravity were included. At different time points (baseline, 1 h/24 h after parabolic flight), venous blood was drawn and analyzed by the use of ELISA. Results: sST2 evidenced a significant decrease 24 h after parabolic flight (baseline vs. 24, p = 0.009; 1 h vs. 24 h, p = 0.004). A similar finding was observed for GDF-15 (baseline vs. 24 h, p = 0.002; 1 h vs. 24 h, p = 0.025). The suPAR showed a significant decrease 24 h after parabolic flight (baseline vs. 24 h, p = 0.1726; 1 h vs. 24 h, p = 0.009). Fetuin-A showed a significant increase at 1 h and 24 h after parabolic flight (baseline vs. 24 h, p = 0.007; 1 h vs. 24 h, p = 0.04). H-FABP and IL-33 showed no significant differences at all time points. Conclusion: Our results suggest a reduction in cardiac stress induced by exposure to gravitational changes. Moreover, our findings indicate an influence of gravitational changes on proliferative processes and calcium homeostasis.

Cardiac output response to standing and treadmill walking

1961 ◽  
Vol 16 (2) ◽  
pp. 283-288 ◽  
Author(s):  
John T. Reeves ◽  
Robert F. Grover ◽  
S. Gilbert Blount ◽  
Giles F. Filley
Keyword(s):  
Cardiac Output ◽  
Oxygen Uptake ◽  
Venous Blood ◽  
Normal Subjects ◽  
Treadmill Walking ◽  
Whole Body ◽  
Output Response ◽  
Total Body ◽  
Response To Exercise ◽  
Oxygen Difference

Cardiac output measurements during cardiac catheterization were obtained in normal subjects for several grades of treadmill exercise. Femoral venous blood was sampled and the A-V oxygen difference for the exercising leg obtained. Measurements of central and femoral A-V oxygen difference and total oxygen uptake were also obtained in normal subjects during supine rest and during standing. When subjects merely stood, the A-V oxygen difference for the leg increased (whether the leg bore weight or not) much more than did that for the whole body. During treadmill walking femoral A-V oxygen difference was usually no greater than that during standing. Cardiac output was smaller and total body A-V oxygen difference was greater for treadmill walking than for supine bicycle exercise in which comparable levels of oxygen uptake were achieved. It is clear that change in posture alters the cardiac output response to exercise. An important aspect of the altered response was a marked difference in the circulation within the leg for these two postures both at rest and during exercise. Submitted on August 8, 1960

Pharmacokinetics of Inhaled Liposome-encapsulated Fentanyl

1995 ◽  
Vol 83 (2) ◽  
pp. 277-284. ◽  
Author(s):  
Orlando R. Hung ◽  
Sara C. Whynot ◽  
John R. Varvel ◽  
Stephen L. Shafer ◽  
Michael Mezei
Keyword(s):  
Healthy Volunteers ◽  
Intravenous Administration ◽  
Venous Blood ◽  
Volume Of Distribution ◽  
Sustained Drug Release ◽  
Future Studies ◽  
Time To Peak ◽  
Drug Molecules ◽  
Peak Absorption ◽  
The Mean

Background Pulmonary administration of fentanyl solution can provide satisfactory but brief postoperative pain relief. Liposomes are microscopic phospholipid vesicles that can entrap drug molecules. Liposomal delivery of fentanyl has the potential to control the uptake of fentanyl by the lungs and thus provide sustained drug release. To demonstrate that inhalation of a mixture of free and liposome-encapsulated fentanyl can provide a rapid increase and sustained plasma fentanyl concentrations (CfenS), this study determined the pharmacokinetic profiles after the inhalation of free and liposome-encapsulated fentanyl in healthy volunteers. Methods After obtaining institutional approval and informed consent, ten healthy volunteers (five men, five women) were studied. Each subject received 200 micrograms intravenous fentanyl and inhaled 2,000 micrograms of free (50%) and liposome-encapsulated fentanyl (50%) on separate occasions. Frequent venous blood samples were collected, and CfenS were determined by radioimmunoassay. The pharmacokinetics and absorption characteristics of the inhaled mixture of free and liposome-encapsulated fentanyl were determined using moment analysis and least-squares numeric deconvolution. Results The mean (+/- SD) volume of distribution at steady-state and clearance of fentanyl after the intravenous administration were comparable to previous studies: 435 +/- 1821 and 0.584 +/- 0.209 l.min-1, respectively. The mean (+/- SD) peak Cfen was significantly greater for the intravenous administration compared to the aerosol mixture of free and liposome-encapsulated fentanyl (4.67 +/- 1.87 vs. 1.15 +/- 0.36 ng.ml-1). However, CfenS at 8 and 24 h after aerosol administration were greater compared to intravenous (0.25 +/- 0.14 and 0.12 +/- 0.16 ng.ml-1 for aerosol versus 0.16 +/- 0.10 and 0.05 +/- 0.06 ng.ml-1 for intravenous). The peak absorption rate, time to peak absorption, and bioavailability after inhalation were 7.02 (+/- 2.34) micrograms.min, -1(16) (+/- 8.0) min, and 0.12 (+/- 0.11), respectively. Conclusions The data suggest that this analgesic method offers a simple and noninvasive route of administration with a rapid increase of Cfen and a prolonged therapeutic fentanyl concentration. Future studies are required to determine the optimal liposome composition that would produce a sustained stable Cfen within analgesic therapeutic concentrations.

scholarly journals Pharmacokinetics and Metabolism of [14C]Ribavirin in Rats and Cynomolgus Monkeys

2003 ◽  
Vol 47 (4) ◽  
pp. 1395-1398 ◽  
Author(s):  
Chin-Chung Lin ◽  
Li-Tain Yeh ◽  
Trong Luu ◽  
David Lourenco ◽  
Johnson Y. N. Lau
Keyword(s):  
Oral Dose ◽  
Oral Administration ◽  
Oral Absorption ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Total Radioactivity ◽  
Cynomolgus Monkeys ◽  
Elimination Half ◽  
Extensive Metabolism ◽  
Total Body

ABSTRACT Absorption, pharmacokinetics, distribution, metabolism, and excretion of [14C]ribavirin were studied in rats (30 mg/kg of body weight) and cynomolgus monkeys (10 mg/kg) after intravenous (i.v.) and oral administration. The oral absorption and bioavailability were 83 and 59%, respectively, in rats and 87 and 55%, respectively, in monkeys. After i.v. administration, the elimination half-life (t [1/2]) was 9.9 h in rats and 130 h in monkeys and the total body clearance was 2,600 ml/h/kg in rats and 224 ml/h/kg in monkeys. The apparent volume of distribution was 11.4 liter/kg in rats and 29.4 liter/kg in monkeys. There was extensive distribution of drug-derived radioactivity into red blood cells and extensive metabolism of ribavirin in rats and a lesser degree of metabolism in monkeys. Excretion of total radioactivity in urine from rats accounted for 84% of the i.v. dose and 83% of the oral dose, whereas that from monkeys accounted for 47% of the i.v. dose and 67% of the oral dose. Several metabolites were observed in plasma and urine from both species. The amount of unchanged ribavirin in urine from both species was quite small after either i.v. or oral administration.

Renal arginine metabolism in fasted rats with subacute short bowel syndrome

1998 ◽  
Vol 95 (4) ◽  
pp. 409-418 ◽  
Author(s):  
Cornelis H. C. DEJONG ◽  
Carlo F. M. WELTERS ◽  
Nicolaas E. P. DEUTZ ◽  
Erik HEINEMAN ◽  
Peter B. SOETERS
Keyword(s):  
Body Weight ◽  
Sham Group ◽  
Acid Metabolism ◽  
Specific Activity ◽  
Renal Plasma Flow ◽  
Venous Blood ◽  
Small Bowel Resection ◽  
Whole Body ◽  
Total Body ◽  
Fasted Rats

1.Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools. 2.Renal amino acid metabolism was studied 24 ;h after 75% small bowel resection in rats fasted overnight (16 ;h) (n = 12; total fast 40 ;h). Sham-operated (n = 9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n = 8/n = 7). During anaesthesia, l-(2,3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover. 3.Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23±3 versus 44±6 ;μM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36±7 and 38±6 ;nmol·min-1·100 ;g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 ;nmol·min-1·100 ;g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly. 4.In conclusion, net renal arginine production is reduced 24 ;h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production.

Ceftriaxone Pharmacokinetics during Iatrogenic Hydroxyethyl Starch-induced Hypoalbuminemia

2000 ◽  
Vol 93 (3) ◽  
pp. 735-743 ◽  
Author(s):  
Olivier Mimoz ◽  
Stéphan Soreda ◽  
Christophe Padoin ◽  
Michel Tod ◽  
Olivier Petitjean ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Hydroxyethyl Starch ◽  
Venous Blood ◽  
Drug Distribution ◽  
Volume Of Distribution ◽  
Reversed Phase ◽  
Pharmacokinetic Parameters ◽  
Antibiotic Administration ◽  
Time Curve ◽  
The Impact

Background Although various drugs used by anesthesiologists highly bind to plasma proteins, the impact of iatrogenically induced hypoproteinemia on their pharmacologic effects has never been investigated. The authors determined the pharmacokinetics of ceftriaxone, a cephalosporin that binds strongly to albumin in postsurgical patients with hydroxyethyl starch-induced hypoalbuminemia. Methods Eleven hypoalbuminemic (serum albumin < 25 g/l) patients and age (+/- 5 yr)-, sex-, and body surface area (+/- 10%)-matched healthy volunteers received a 2-g ceftriaxone dose infused over a 15-min period. Fourteen venous blood samples were collected during the 24-h study period. Free ceftriaxone concentrations were determined by ultrafiltration. Antibiotic concentrations in plasma and ultrafiltrate were measured by ion-paired reversed-phase chromatography. The pharmacokinetic parameters derived from total and free antibiotic concentrations were determined using a noncompartmental method. Data are expressed as median and range. Results The pharmacokinetic parameters derived from total ceftriaxone concentrations were similar for the two groups, except for the median corrected volume of distribution at steady state, which was increased (P = 0.05) to 0.18 l/kg (range, 0. 11-0.29 l/kg) in patients, compared with 0.15 l/kg (range, 0.13-0.22 l/kg) in volunteers. The area under the free ceftriaxone concentration-time curve was twice as high in patients as in volunteers (median 192, range 114-301 vs. median 122, range 84-169 h. mg-1. l-1;P = 0.03). Moreover, the free ceftriaxone concentration remained more than 4 mg/l during more time in patients (median, 16. 7; range, 12.6-21.4 vs. median, 11.1; range, 6.0-19.0 h; P = 0.03). Conclusions Compared with healthy volunteers, patients with iatrogenic hypoalbuminemia have higher free ceftriaxone concentrations during the 24 h after antibiotic administration. This modification increases drug distribution into extravascular space and may enhance effectiveness.

scholarly journals Pelvic Injury Risk Curves for the Military Populations From Lateral Impact

2021 ◽  
Vol 186 (Supplement_1) ◽  
pp. 424-429
Author(s):  
Narayan Yoganandan ◽  
Tyler F Rooks ◽  
Valeta Carol Chancey ◽  
Frank A Pintar ◽  
Anjishnu Banerjee
Keyword(s):  
Confidence Interval ◽  
Body Mass ◽  
Injury Risk ◽  
Whole Body ◽  
Pelvic Injury ◽  
Published Data ◽  
Total Body Mass ◽  
Military Populations ◽  
Total Body ◽  
Risk Curves

ABSTRACT Introduction Current methods for transporting military troops include nonstandard seating orientations, which may result in novel injuries because of different types/directions of loading impact. The objective of this study is to develop pelvic injury risk curves (IRCs) under lateral impacts from human cadaver tests using survival analysis for application to military populations. Methods Published data from lateral impacts applied to whole-body cadaver specimens were analyzed. Forces were treated as response variables. Demographics and body mass index (BMI) were covariates. Injury risk curves were developed for forces without covariates, for males, females, 83 kg body mass, and 25 kg/m2 BMI. Mean and ± 95% confidence interval IRCs, normalized confidence interval sizes at discrete risk levels, and quality indices were obtained for each metric-covariate combination curve. Results Mean age, stature, total body mass, and BMI were 70.1 ± 8.6 years, 1.67 ± 0.1 m, 67.0 ± 14.4 kg, and 23.9 ± 3.97 kg/m2, respectively. For a total body mass of 83 kg, peak forces at 10%, 25%, and 50% probability levels were 5.7 kN, 7.4 kN, and 9.6 kN, respectively. For males, peak forces at the 10%, 25%, and 50% probability levels were 4.8 kN, 6.4 kN, and 8.4 kN, respectively. For females, peak forces at the 10%, 25%, and 50% probability levels were 3.0 kN, 4.0 kN, and 5.2 kN, respectively. Other data and risk curves are given. Conclusions The IRCs developed in this study can be used as injury criteria for the crashworthiness of future generation military vehicles. The introduction of BMI, sex, and total body mass as covariates quantified their contributions. These IRCs can be used with finite element models to assess and predict injury in impact environments to advance Soldier safety. Manikins specific to relevant military anthropometry may be designed and/or evaluated with the present IRCs to assess and mitigate musculoskeletal injuries associated with this posture and impact direction.

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