PET Evaluation of Hemorrhagic Shock and Resuscitation
Principal Investigator: Vibhudutta Awasthi
Abstract: [unreadable] DESCRIPTION (provided by applicant): In the USA, trauma kills approximately 150,000 people each year. Despite such an impact on health care, fluid resuscitation in trauma continues to be a debatable issue. Crystalloids or colloids are commonly used and these fluids augment O2 delivery only by increasing preload. The only fluids that can increase both O2- carrying capacity and preload are hemoglobin based products. Thus, the long-term goal of this research is to develop encapsulated hemoglobin as a complete and universal resuscitative fluid to address multifaceted pathophysiology of hemorrhagic shock. Liposome encapsulated hemoglobin (LEH), as well as other hemoglobin-based O2 carriers (HBOCs), have undergone extensive evaluation. But, an efficient O2 carrier is not necessarily an efficient O2 delivery vehicle. PET has the capability to visually, quantitatively and non- invasively assess O2 delivery and metabolism in response to resuscitation. HYPOTHESES 1) LEH delivers O2 to the brain in the same fashion as RBCs, 2) cerebral O2 delivery from LEH is sustained for a longer period of time than the unencapsulated HBOCs, and 3) LEH encapsulating high-affinity hemoglobin delivers more O2 to the brain than LEH containing low-affinity hemoglobin in severe blood loss. SPECIFIC AIMS are: 1). Develop and validate image-derived cardiac time-activity curve as an arterial input function in MicroPET investigation of rat cerebral oxygen metabolism (CMRO2). 2). Investigate the effect of oxygen affinity of hemoglobin in LEH on cerebral oxygen metabolism after resuscitation in a rat model of hemorrhagic shock. 3).Evaluate the improvement in CMRO2 and energy metabolism after LEH resuscitation against standard resuscitative fluids in a rat model of hemorrhagic shock. We will perform microPET imaging with O-15 radiotracers (O2 gas, CO gas and H2O) to determine CMRO2 and CBF. A rat model of hemorrhagic shock will be resuscitated with LEH, whole blood, Ringer's lactate solution and 5% albumin. Cerebral energy metabolism will be established by tissue markers of aerobic metabolism. This is an innovative proposal that utilizes state-of-the-art imaging technology in a small animal model. The study will not only address important issues pertaining to oxygen metabolism in shock and resuscitation, it may also be useful in evaluation of other artificial oxygen carriers undergoing preclinical and clinical trials. [unreadable] [unreadable] [unreadable]
Funding Period: 2006-08-01 - 2009-07-31
more information: NIH RePORT
- Magnetic resonance spectroscopy for evaluation of liposome-encapsulated hemoglobin as a resuscitation fluidVibhudutta Awasthi
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA
Artif Cells Blood Substit Immobil Biotechnol 38:69-78. 2010..The results indicate the utility of MRS to monitor cerebral metabolism in hemorrhage/resuscitation. The data is also supportive of the new LEH formulation as an oxygen carrier...
- Cerebral oxygen delivery by liposome-encapsulated hemoglobin: a positron-emission tomographic evaluation in a rat model of hemorrhagic shockVibhudutta Awasthi
Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
J Appl Physiol (1985) 103:28-38. 2007....
- Improved formulation of liposome-encapsulated hemoglobin with an anionic non-phospholipidHrushikesh Agashe
Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, 1110 North Stonewall Avenue, Oklahoma City, OK 73117, USA
Colloids Surf B Biointerfaces 75:573-83. 2010..The LEH formulation with novel anionic lipid and high hemoglobin content reported in this article is an improvement from the past preparations...