In direct response to the NIH-BRG announcement, our emphasis is to develop and test bioengineering technologies and methods useful for characterizing vascular complications in an animal model, and to study the efficacy of a biomaterial (artificial blood/blood substitute) in a bioengineering research project. Our intention is not to test a specific mechanistic hypothesis (as in a standard R01 application), but rather to develop, enhance, build (assemble) and test bioengineering technologies and methods as expected in a BRG study. Based on pilot data from our laboratories, we have developed the following Specific Aims: (1) Use the UC Davis canine hypovolemic model as the center piece, and taking advantage of the state-of-the-art veterinary school animal facilities and animal surgery expertise, design and build a bioengineering research station (complete with monitoring instrumentation, measuring devices, systemic study accessories and an in vivo microcirculation-dedicated intravital microscope system) around it for hypovolemic shock and blood substitute resuscitation research. (2) Test the functionality of the research station built in Specific Aim (1) by using it to study mongrel dogs pre- and post- hemorrhagic shock --- serves to generate baseline references. (3) Apply the tested technologies and methods from Specific Aim (2) to study and quantify the effects of artificial blood resuscitation in hypovolemic dogs (using a commercially available blood substitute approved for canine use) --- serves to confirm the functionality of this bioengineering research station as a research base to evaluate blood substitute safety and efficacy. The emphasis of this BRG is to build a bioengineering research station around a canine hypovolemic model. However, in Specific Aims (2) and (3), we will also be conducting an evaluation of a commercially available blood substitute with emphasis on its physical and rheological effects on the microcirculation and its hemodilution characteristics, in addition to simultaneously studying its systemic effects and oxygen-delivery capability under monitored conditions.
