3DT HOLDINGS, LLC — Department of Health and Human Services SBIR Phase II: NHLBI

Description

ABSTRACT ST segment myocardial infarctionSTEMIis a serious acute coronary condition that affectsAmericans each year and results in significant U Shealthcare costs$B year for acute MI treatmentSTEMI mortality directly relates to the extent of the total myocardial injury and even with thegold standardof reperfusionup toof the total myocardial injury can be related to reperfusion injuryRIthat occurs directly following the restoration of blood flow to the ischemic myocardiumMild hypothermiaMHtemperatureCprovides cardioprotection and may greatly diminish RI by reducing myocardial metabolic demandfree radical creationand total infarct sizeHoweverMH and all other current therapy optionspharmacologicsetchave been largely unsuccessful in the treatment of RIThis is due to the fact that the arterial obstruction does not allow for therapy delivery to the region of interest until PCI is completedwhich would be too late to prevent RITo address this limitationwe have developed and validated a novelcatheter based method of selective auto retroperfusionSARPthat regulates the pressure to the venous systemltmmHgto locally deliver cooled arterial bloodMH SARPto the ischemic regionImportantlyresults from our phase I studies have demonstrated remarkable and unprecedented reduction in infarct sizein a swine model of anterior LV MI which corresponded with an attenuation of markers for ischemiccardiac troponinreperfusionST segment depressionand cellular injuryoxygenglucose and lactate uptake as well as caspaseexpressionInterestinglySARP alone also significantlyreduced these indices to near equivalent levels suggesting that the primary benefit may be derived by oxygen delivery without the need for MHIn order to advance these outstanding proof of concept results towards a first in humanhoweverthe SARPMH therapeutic approach and mechanism must be critically challenged under more extensiveclinically translational conditionsIn particularthe therapy must remain effective during longer ischemic and shorter retroperfusion periods while minimizing disruption to clinical workflowdoor to balloon timeand overall risk to patientsAccordinglythe logical extension of the findings obtained during phase I are addressed by the following specific aimsChronic Animal Studiesto determine feasibility and integration into clinical workflow in a chronic model of anterior LV STEMIandSafety studies for Pre IDE SubmissionTo obtain GLP dataand prepare Pre IDE submission package for first in manThis Phase II study addresses a highly significant national and worldwide clinical need for reducing RI in STEMI patients and has the ability to reach across various NIH Institutes and Centers including the NIDDK and NHLBI