Identifying the rules of engagement enabling in silicoleukocyte rolling activation and adhesionJonathan Tang C Anthony HuntUniversity of California San FranciscoThe UCSFUCB Joint Graduate Group in Bioengineering

Objectives Leukocyte rolling activation and adhesion onendothelial cell surfaces are key events during leukocyterecruitment to tissues during the inflammatory process Theinteractions between leukocytes and endothelial cell surfacesduring rolling activation and adhesion are complex and involveligand-binding events between several combinations of receptor-ligand pairs Spatially restricted signaling events betweenchemokine receptors and local integrins as well as lateral diffusionand clustering of integrins are thought to play important roles inmediating the transition from rolling to adhesion The objective ofthis project was to develop a novel computational model thataimed at gaining a fundamental understanding of the spatiotem-poral events and key rules of engagement that determine when andhow leukocytes are able to adhere to endothelial cell surfacesduring inflammatory conditionsMethods We used the synthetic modeling approach to construct amultilevel multiagent in silico model of leukocyte rollingactivation and adhesion Object-oriented software componentswere designed verified plugged together and then operated inways that represent the mechanisms and processes believedresponsible for leukocyte rolling and adhesion The in silico systemconstructed was a discrete event discrete space and discrete timeanalogue of the entire parallel plate flow chamber systemcommonly used to study leukocyte rolling and adhesion in vitroThis modeling approach allowed us to represent the spatial anddiscrete event phenomena that are thought to occur in vitro andin vivoResults We previously reported details of the model and initialresults of in silico rolling and adhesion on P-selectin and VCAM-1substrate in the presence of GRO-alpha chemokine (PMID17408504) in silico leukocyte movement is a function of (1)number and type of bonds and (2) location of the bond-containingpatches at the interface Our current effort has extended the modeland increased resolution to enable exploration of the role of lateraldiffusion and clustering of LFA-1 integrin in mediating rolling andadhesion to ICAM-1 substrateConclusions These new methods represent important progress ingaining a fundamental understanding of the spatiotemporalevents and key rules of engagement that determine when andhow leukocytes adhere to endothelial cell surfaces duringinflammation The current model and results represent animportant step in developing scientifically useful validatedsimulations of leukocyte recruitment under physiologic andpathophysiologic conditions

doi101016jjcrc200710017

Impact of analysis interval on heart rate and blood pressurevolatility in a murine model of sepsisAnupam Gupta Bryan Foley Josh WeinstockKarine Hageboutros Jad Skaf Joseph E ParrilloSergio Zanotti Steven M HollenbergDepartment of Cardiology and Critical CareCooper University Hospital Camden NJ USA

Objectives Nonlinear analysis of beta-to-beat heart rate (HR) andblood pressure (BP) variability may provide insights into diseasepathophysiology not available from standard linear measures Wehave used HR and BP volatility (SD variability) as a means ofassessing variability that may minimize artifact-induced error andhave used this method to demonstrate decreased HR and BP volatilityin 5-minute intervals in a murine model of septic shock Shorteranalysis intervals may allow for more detailed time course analysesbut aremore time consuming In this study we examined the effects ofthe time segment of analysis on HR and BP volatility measurementsMethods Radiotelemeters for noninvasive measurement of bloodpressure were implanted into the ascending aorta of C57Bl6 mice(8-12 weeks n = 23) After 5 to 7 days of recovery postimplantationbaseline data were collected for 24 hours The mice were then madeseptic by cecal ligation and puncture (CLP) and resuscitated withfluids and antibiotics every 6 hours controls underwent shamligation HR and systolic BP were calculated from BP waveformsand HR and BP SDswere calculated in on each 1- 5- and 10-minutetime segments for the 72-hour course of the experiment For eachanimal the SD cutoff of both HR and BP that represented the lowest5 was determined and the of low SDs (low volatility) in theentire experimental period was defined by this cutoffResults Threshold values of the 5 SD cutoff did not differ for1- 5- and 10-minute analysis intervals for either HR (206 plusmn 125340 plusmn 184 382 plusmn 160 respectively P = NS) or BP (19 plusmn 0430 plusmn 06 39 plusmn 09 respectively P = NS) HR volatility differedsignificantly between control and septic groups for all 3 analysisintervals (1 minute 44 plusmn 43 vs 432 plusmn 270 P = 01 5 minutes47 plusmn 38 vs 455 plusmn 326 P = 02 10 minutes 48 plusmn 72 vs 471 plusmn337 P = 02) BP volatility differed significantly between controland septic groups for the 5- and 10-minute intervals (5 minutes117 plusmn 46 vs 392 plusmn 196 P = 01 10 minutes 139 plusmn 58 vs453 plusmn 235 P = 02) Low BP volatility intervals were morecommon for septic than control animals for the 1-minutemeasurement interval as well (380 plusmn 241 vs 146 plusmn 50) butdid not reach statistical significance (P = 07) Examination of BPwaveforms revealed that increased artifact influenced BP volatilityin the 1-minute analysis intervalConclusions less demanding and more intuitive as a means ofmeasuring variability than spectral analysis and artifact increasesSD and so biases the data to the null hypothesis In our study thisdecreased the sensitivity of the 1-minute analysis interval to detectchanges between experimental and control subjects The use oflonger-time segments or better filtering techniques may benecessary to minimize the influence of measurement artifacts inBP volatility analysis

doi101016jjcrc200710018

Integer heart rate multiscale entropy and variability earlyindependent predictors of mortality in 3145 traumaICU patientsPatrick Norrisab Judith Jenkinsa John MorrisacaDivision of Trauma Burn and Surgical Critical CareVanderbilt UniversitybDepartment of Biomedical Engineering Vanderbilt UniversitycDepartment of Biomedical Informatics Vanderbilt University

Objectives We have shown that integer heart rate multiscaleentropy (MSE) and variability (HRV) separately predict trauma

341Abstracts