El Rasheid Zakaria, MD, PhD. 12514 Bridgetown Place, Louisville, KY 40245 (502)339-7203, (502)468-3855 [email protected]
Education
	University of Lund, Lund, Sweden
	Ph.D. in Nephrology and Physiology		1995
	Dissertation: “Fluid and solute transport into and out of the peritoneal cavity: Experimental studies in the rat” Honors: Dissertation passed “with Distinction” Ph.D. Components: ·       Quantitative description of solute clearance and water removal in peritoneal dialysis. ·       Mechanisms of fluid exchange across the blood-peritoneal barrier. ·       The role and contribution of peritoneal lymphatics in peritoneal dialysis. ·       Validation of the three-pore model of peritoneal permselectivity. ·       How to enhance the efficacy of peritoneal solute removal? ·       Handling of mass-balance equations. Mathematical modeling and computer simulations of trans-peritoneal exchange. ·       The role of trans-endothelial water-selective ultra pores (Aquaporin-1) in peritoneal dialysis. ·       The effect of increased intraperitoneal hydrostatic pressure on fluid and Protein transport.
	Zagazig University, Zagazig, Egypt
	M.D.		1983
	Professional Experience Assistant Professor, University of Louisville, KY.                 03/2004–Present Research Associate, University of Louisville, KY.                09/1999–03/2004 Instructor in Medicine, The University of Rochester, NY.      04/1996-06/1998 Extra-Physician and PhD Candidate, University of Lund.     09/1989–12/1995 Senior Medical Officer and Outpatient Director, Abu Arish, KSA.                                                                 05/1987–07/1989                                                                    Senior Medical Officer and Hospital Director, Abu Arish Hospital for Chest Diseases.                               10/1986–04/1987 Senior Medical Officer, Abu Arish General Hospital, KSA.                                                                                  09/1985–09/1986    Senior Medical Officer, Soba University Hospital, Khartoum, Sudan.                                                              08/1984–08/1985 House Officer, Soba University Hospital, Khartoum, Sudan.                                                              06/1983–08/1984
AWARDS
		·    Postdoctoral Fellowship, University of Rochester, Rochester, NY	1996 – 1999
		·    Instructor in Physiology and Biophysics, University of Louisville, Louisville, KY. ·    Winner of the Outstanding Abstract Award for the best abstract submitted to the 14th Annual Conference on Peritoneal Dialysis. Orlando, Fl 1994. ·    Nominated for the Maher Award, established by the International Society of Peritoneal Dialysis to honor young investigators who have contributed significantly to the field of Peritoneal Dialysis. ·    Invited speaker at the meeting of the International Society of Peritoneal Dialysis, Stockholm, Sweden 1995. ·    Invited speaker at the 21st Annual Conference on Dialysis, New Orleans, Louisiana, 2001.                                                                                        ·    Winner of the University of Louisville Performance Award 2002. ·    Invited speaker at the 24th Annual Conference on Dialysis, San Antonio, Texas, 2004. ·    Invited speaker at the first joint meeting of the international and European Societies for peritoneal dialysis, Amsterdam, the Netherlands 2004. ·    Invited speaker at the first North American Chapter of the ISPD, Chicago.   Scientific Journal Appointments: 1999-Present   Referee, Kidney International   Special Appointment: Former committee member and team leader of the Regional Tuberculosis Control Program (RTCP), Gizan, Saudi Arabia. Participant in the Epidemiological studies attached to the program (PhD thesis) presented by Dr. A.A. Osman, in collaboration with the Ministry of Health, Saudi Arabia, Copenhagen University, Denmark, and the Statens Serum Institute, Copenhagen, Denmark.	1994                    1995                2001                2004                2004              2004                  2005
Teaching Experience
		University of Louisville
		Lecturer– “The peritoneal cavity as a therapeutic route”	2005
		Developed syllabus and overall course structure.
		Adjunct Instructor– “Microvascular control mechanisms in shock and sepsis”	2004
		Developed syllabus and overall course structure.
		Instructor – Animal models	1999- 2005
		Developed syllabus and overall course structure, including weekly lab practicum.
		Teaching Assistant – to Professor R.N. Garrison in “Role of blood flow in low-flow states.”	2005
		Collaborated on curriculum and course structure, met with students upon request,  Trainees 1) Ola Carlsson: Awarded PhD. 2) Na Li: Awarded PhD. 3) Michelle Hunt: Awarded MS. 4) James E. Campbell PhD student. 5) Anuj M. Patel: PhD student. 6) Ryan T. Hurt: PhD student. Seminars and invited talks   ·          Regular participant in journal club meetings at the departments of physiology & biophysics as well as the Nephrology department since 1989. ·           Nordisk Nyredager (Nordic Nephrology meeting). Reykjavik, Iceland. 1993. ·           American Society of Nephrology, Boston, USA, 1993. ·           Nordic meeting in Nephrology. Göteborg, Sweden, 1993. ·           Nordic meeting in Nephrology. Uppsala, Sweden, 1994. ·           International Congress in Physiology & Pharmacology, Copenhagen, Denmark. 1994. ·           The 14th annual Conference on Peritoneal Dialysis. Orlando, Florida. USA.1994 ·           How to write and illustrate a scientific paper. Lund University, Sweden. 1993. ·           The experimental animal. Lund University, Sweden. 1992. ·           Dialysis, the extracorporal treatment. Postgraduate national training program arranged by the  Socialstyrelsen. Lund University, Sweden. 1995. ·           International Society of Peritoneal Dialysis, Stockholm, Sweden. 1995. ·           Training program for authorized use of radioactive materials. University of Rochester, USA, 1996. ·           American Society of Nephrology, New Orleans, USA. 1996 ·           American Society of Nephrology, San Antonio, USA, 1997. ·           American Society of Nephrology, Philadelphia, USA, 1998. ·           Experimental biology, San Diego, CA , USA 2000 ·           21ST Annual Conference on dialysis, New Orleans, 2001. ·           Shock Society, Marco Iceland, FL, 2001. ·           Microvascular reactivity in peritoneal dialysis, Louisville, KY 2003. ·           The paradox: Peritoneal dialysis is a novel treatment of hemorrhagic shock, Louisville, KY 2003. ·           The peritoneal cavity as a route for chemotherapeutics delivery. Louisville, KY 2004. ·           The vascular endothelium in hemorrhagic shock and resuscitation. Louisville, KY 2004. ·           24th Annual Conference on Dialysis, San Antonio, TX 2004. ·           The blood-peritoneal barrier: From bench to bed sides. Louisville, KY 2005. ·           The first North American Chapter of the ISPD, Chicago, IL 2005.
Experience in collaboration with the industry
		Recently, a new technique to deliver high-energy phosphates directly into the cytosol of normal or ischemic cells was developed by a Louisville-based company (VitaTech). This is achieved by specially formulated, highly fusogenic, unilamellar lipid vesicles that contain magnesium-ATP (VitaSol™). This technique has the potential to reduce or eliminate many detrimental effects caused by ischemia by directly replenishing intracellular ATP levels. Once delivered to the cell, VitaSol™ can maintain cell metabolism and membrane functions. VitaSol™ is available in aqueous or freeze-dried forms. I was recruited by VitaTech to lead a research effort to utilize VitaSol™ in our hemorrhage/resuscitation model. We have made considerable improvements to VitaSol™ with respect to formulation, stability, and defining pharmacokinetics of the product after intravenous or intraperitoneal administration. A SBIR grant to advance our research effort is pending.     Lipid vesicles and stability The commercial production of liposomes has been very limited. One reason is that lipid vesicles are physically and chemically unstable. Maximum shelf-life of laboratory produced vesicles is on the order of hours to days. The FDA has set guidelines for a pharmaceutical agent in terms of stability and efficacy. The current method under which VitaSolTM is produced does not meet the FDA guidelines for stability and efficacy. VitaTech, LLC is currently developing a means to freeze-dry VitaSolTM which increases the products' shelf-life to18 months. Our preliminary data have show that freeze-dried VitaSolTM has similar efficacy as freshly prepared VitaSolTM This technique allows lipid vesicles, and specifically VitaSolTM to have a much longer shelf-life and greater acceptance in the medical and lay community.   Commercial Opportunity            Each year millions of individuals suffer from severe blood loss due to trauma, surgical procedures, and a pathophysiological event.  While crystalloid resuscitation and whole blood infusion have saved the lives of many individuals who have experienced hemorrhagic shock, these procedures are limited and in many cases fail.  Our preliminary data indicates that high energy phosphate delivery using VitaSol has a significant beneficial affect.  A pending Phase I proposal will examine the efficacy of VitaSolTM in a rat model of hemorrhagic shock.  These rodent studies will be further extended into large animal efficacy studies and pre-clinical toxicity studies in Phase II.  If successful, this highly innovative approach to hemorrhagic shock will undergo a Phase I clinical trial.  Given the enormous expense associated with the treatment of this pathophysiological state, our approach will save hundreds of millions of dollars in patient costs.  In addition, given the parallel development of a stabile version of VitaSolTM by freeze-drying, it is likely that Clinical Trial Material will be developed during the course of our research effort allowing the drug candidate to be safely and easily used by clinicians.
Publications and papers
		·    Zakaria ER, R. N. Garrison, T. Kawabe, and P. D. Harris. Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation. J.Trauma 58 (3):499-506, 2005. ·    Zakaria ER, Ehringer WD, Nina T, Na Li, Garrison R.N. Direct energy delivery improves tissue perfusion after resuscitated shock. Surgery, In press, 2005. ·    Zakaria ER, Michelle C. Hunt, Harris PD, Garrison RN. On the Disparity in Osmolarity-induced Vascular Reactivity. JASN, In press 2005. ·    Nina T., E.R. Zakaria, R.N. Garrison. Hypertonic saline resuscitation improves intestinal microcirculation in a rat model of hemorrhagic shock. Manus 2005. ·    N. Li, P. D. Harris, ER Zakaria, P. J. Matheson, and R. N. Garrison. Microvascular responses to adenosine help explain functional and pathologic differences between intestinal segments. Am.J.Surg. 188 (5):526-531, 2004. ·    R. N. Garrison, A. A. Conn, P. D. Harris, and E.R. Zakaria. Direct peritoneal resuscitation as adjunct to conventional resuscitation from hemorrhagic shock: a better outcome. Surgery 136 (4):900-908, 2004. ·    Zakaria ER, Garrison RN, Spain DA, Harris PD. Impairment of endothelium-dependent dilation response after resuscitation from hemorrhagic shock involved post-receptor mechanisms. Shock, 21(2) 175-181, 2004. ·    Zakaria ER, Garrison RN, Kawabe T, Harris PD. Role of neutrophils on shock/resuscitation-induced intestinal arteriolar derangements. Shock, 21(3):248-53, 2004. ·    Kawabe, T, Zakaria ER,  Harris PD, Garrison RN: Peritoneal dialysis solutions contract large arteries through endothelium-independent prostanoid pathways. Adv Perit Dial (20): 177-183, 2004. ·    Zakaria ER, Garrison RN, Spain DA, Matheson PJ, Harris PD, Richardson DJ. Intraperitoneal resuscitation improves intestinal blood flow following hemorrhagic shock. Ann Surg 237(5):704-713, 2003. ·    T. Kawabe, P. D. Harris, E. R. Zakaria, and R. N. Garrison. Sepsis alters vessel contraction by adrenoreceptor-induced nitric oxide and prostanoid. J Surg Res. 110 (2):352-359, 2003. ·    Zakaria ER, Spain DA, Harris PD, Garrison RN: Generalized dilation of the visceral microvasculature by peritoneal dialysis solutions. Perit Dial Int 22:593, 2002. ·    Zakaria ER, Spain DA, Harris PD, Garrison RN: Resuscitation regimens for hemorrhagic shock must contain blood. Shock 18:567, 2002. ·    Flessner MF Lofthouse J, Zakaria ER. Inproving contact area between the peritoneum and intraperitoneal therapeutic solutions. J Am Soc Nephrol  12:807-813, 2001. ·    Zakaria ER, Lofthouse J, Flessner MF. The effects of  intraperitoneal pressures on tissue water of the abdominal muscle.  Am J Physiol. 278:F875-F885, 2000. ·    Zakaria ER, Lofthouse J, Flessner MF. In vivo Effects of hydrostatic pressure on the interstitium of abdominal wall muscle. Am J Physiol 279: H517-H529, 1999. ·    Zakaria ER, Lofthouse J, Flessner MF. Intraperitoneal pressures modulate partitioning of total tissue water during peritoneal dialysis. Perit Dial  Int  Suppl. 2, S208-211,1999. ·    Zakaria ER, Lofthouse J, Flessner MF. In vivo Hydraulic conductivity of muscle: effects of  hydrostatic pressure. Am. J. Physiol. 273:H2774-H2782,  1997. ·    Flessner MF, Lofthouse J, Zakaria ER. In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal. Am. J. Physiol. 273:H2783-2793, 1997. ·    Zakaria ER, Carlsson O, Rippe B. Limitation of small solute exchange across the visceral peritoneum: Effects of vibration. Perit Dial Int 17, 72-97, 1997. ·    Zakaria ER, Simonsen O, Rippe A, Rippe B. Transport of tracer albumin from peritoneum to plasma: role of diaphragmatic, visceral, and parietal lymphatics. Am J Physiol 270 (Heart Circ Physiol 39) H1549-H1556, 1996. ·    Zakaria ER, Carlsson O, Sjunnesson H, Rippe B. Liver is not essential for solute transport during peritoneal dialysis. Kidney Int 50: 298-303, 1996. ·    Rippe B, Zakaria ER, Carlsson O. Theoretical analysis of osmotic agents in peritoneal dialysis. What size is an ideal osmotic agent ? Perit Dial Int 16 (Suppl 1) S97-S103, 1996. ·    Carlsson O, Nielson S, Zakaria ER, Rippe B. In vivo inhibition of transcellular water channels (Aquaporin-CHIP) during acute peritoneal dialysis in rats. Am J Physiol 271 (Heart Circ Physiol 40): H2254-2262, 1996. ·    Zakaria ER, Rippe B. Peritoneal fluid and tracer albumin kinetics in the rat. Effects of increases in intraperitoneal hydrostatic pressure. Perit Dial Int 15:118-128, 1995. ·    Zakaria ER, Rippe B. Intraperitoneal fluid volume changes during peritoneal dialysis in the rat. Indicator dilution vs. volumetric measurements. Blood Purif 13: 355-270, 1995.   Zakaria ER. Fluid and solute transport into and out of the peritoneal cavity:   Experimental studies in the rat. University of Lund, Sweden. 1-72, 1995. 12-20-1995. PhD. ·    Osman A, Hakim JG, Lüneborg-Nilsen M, Bentzon MW, Ageel AM, Zakaria ER, Saleem A, Bakdash I. Comparative skin testing with PPD tuberculin, Mycobacterium Avium and M. Scrofulaceum sensitens in school children in Saudi Arabia. Tuber Lung Dis 75: 38-43, 1994. ·    Zakaria ER, Rippe B. Osmotic barrier properties of the rat peritoneal membrane. Acta Physiol Scand 149: 355-364, 1993. ·    Rippe B, Zakaria ER. Lymphatic versus non lymphatic fluid absorption from the peritoneal cavity as related to the peritoneal ultrafiltration capacity and sieving properties. Blood Purif 10: 189-202, 1992. ·
Languages
		·    Arabic – native language ·    English – speak fluently and read/write with high proficiency ·    Swedish – speak, and read with basic competence.
range of skills the candidate can bring to Employer
		·    Ability to work with employer and other international scientists. ·    Clinical prospective of bench research data. ·    More than 15 years experience in the physiology and pathophysiology of peritoneal dialysis, which combines interstitial physiology, vascular biology and immunology, mathematical modeling, statistical methods, unique methodologies such as the tracer dilution technique, histochemistry, intravital microscopy, and quantitative autoradiography. ·    Application of peritoneal dialysis as a technique of direct peritoneal resuscitation (DPR) from trauma and hemorrhagic and septic shocks. This technique which was developed by the candidate during the last 3 years was tested in animal models and few patients with extreme injury scores. This opens a whole new marked for the use of peritoneal dialysis solutions.

Selected published Abstracts

·      Na Li; Harris PD; Zakaria ER; Matheson PJ; Garrison RN. Role of adenosine receptor subtypes in intestinal microvasculature during glucose absorption. Faseb 2005.

·      Na Li; Harris PD; Zakaria ER; Matheson PJ; Garrison RN. Inhibition of Glucose Transporter SGLT-1 Attenuates Glucose-induced
Dilation of Intestinal Microvessels. Faseb 2005.

·      Na Li; Harris PD; Zakaria ER; Matheson PJ; Garrison RN. Nitric Oxide Not K+ATP Channel Involved in A1 Adenosine Receptor-mediated
Intestinal Vasodilation during Glucose Absorption. Faseb 2005.

·      Zakaria ER, Kawabe, T, Harris PD, Garrison RN: Peritoneal dialysis solutions contract large arteries through endothelium-independent prostanoid pathways. Perit Dial Int 24, Suppl 1, S12, 2004.

·      Zakaria ER, Spain DA, Harris PD, Garrison RN. Altered Receptor activity causes microvascular dysfunction after resuscitated hemorrhagic shock. Shock, 2002.

·      Zakaria ER, Spain DA:  Regimens of resuscitation from hemorrhagic shock must contain blood. Shock, 2001.

·      Zakaria ER, Spain DA, Harris PD, Garrison RN. The Paradox: Peritoneal dialysis, A Novel Treatment in Hemorrhagic Shock. Perit Dial Int 21(Suppl. 1), S21, 2001.

·      Zakaria ER, Spain DA, Harris PD, Garrison RN. In vivo quantitative description of visceral microvascular reactivity in peritoneal dialysis. Perit Dial Int 21 (Suppl. 1), S21, 2001

·      Flessner, MF, Zakaria ER, Lofthouse J: Convective transport of immunoglobulin G through muscle interstitium. Faseb J  14: A25, 2000.

·      Zakaria ER, Lofthouse J, Flessner MF.  Improving dialysis: Can peritoneal surface area be enhanced. J Am Soc Nephrol 1999.

·      Zakaria ER, Lofthouse J, Flessner MF. In vivo effects of hydrostatic and osmotic pressures on the interstitium of muscle. Faseb J. 12:A28, 1998.

·      Zakaria ER, Lofthouse J, Flessner MF. Intraperitoneal pressures modulate partitioning of total water content in peritoneal tissue. J Am Soc Nephrol 9:195A, 1998.

·      Zakaria ER, Lofthouse J, Flessner MF. Hydrostatic and osmotic pressures modulate partitioning of tissue water in the abdominal muscle during dialysis. Perit Dial Int 18 (Suppl. 2): S66, 1998.

·      Zakaria ER, Lofthouse J, Flessner MF. Fluid loss from the peritoneal cavity is dependent on dilution and washout of the interstitial matrix. J Am Soc Nephrol 8:294A, 1997.

·      Zakaria ER, Lofthouse J, Flessner MF. Effect of hydrostatic pressure on the interstitial space of muscle. Microcirculation 4:154, 1997.

·      Simonsen O, Zakaria ER, Rippe B. Absorption of labeled red cells and tracer albumin (RISA) from the peritoneal cavity to the blood. Role of diaphragmatic, visceral and parietal lymphatic pathways. EDTA abstract book. 1993.

·      Zakaria ER, Lofthouse J, Flessner MF. Fluid loss from the peritoneal cavity is dependent on dilution and washout of the interstitial matrix. 30th annual meeting (ASN) St. Antonio TX. 1997.

·      Rippe B. Zakaria ER, Carlsson O. Do visceral stagnant fluid films limit the peritoneal exchange of small solutes? Perit Dial Int 1996; 16(Suppl 2): S11.

·      Simonsen O, Zakaria ER, Rippe B. Enhanced transperitoneal small solute exchange during the early portion of the dwell in CAPD patients. Role of the interstitium.    Perit Dial Int, Abstract Seattle meeting 1995.

·      Rippe B. Zakaria ER. Rippe A. Transport of tracer albumin (RISA) from peritoneal cavity to the blood in rat: Role of diaphragmatic, visceral and parietal pathways.  Perit Dial Int 1994; 14 (Suppl 1): S7.

·      Zakaria ER. Rippe B. Validation of the single injection RISA indicator dilution method for assessing intrperitoneal volume as a function of dwell time during peritoneal dialysis in the rat. In (ed) Abstract book of Scandinavian Society of Nephrology (Nordisk Nyredage), Reykjavik, Iceland, 1993; pp 29.

·      Rippe B. Zakaria ER. Peritoneal fluid and albumin kinetics in the rat: effects of increase in intraperitoneal hydrostatic pressure. Perit Dial Int 1993; 13(Suppl 1): S 74.

 

Research Support:

 

COMPLETED RESEARCH PROJECTS:

 

“Intestinal Microvascular Control During the Trauma of Hemorrhagic Shock”

Principal Investigator:  David A. Spain, MD.

Agency: Veteran Administration

Type: Merit Review Grant

Role: Data collection and analysis, literature search and manuscripts preparation.

 

This grant focuses on the effects of acute hemorrhagic shock on the subsequent microcirculatory control in the intestine and on the priming events that occur in the endothelium following hemorrhagic shock. The principal Investigator was introduced to the field of shock research by Dr. Spain and professor Garrison in 1999. Both investigators are active in shock research and utilize similar in vivo video microscopy techniques, such as measurement of microvessel diameters and red blood cell velocity and does share common laboratory support equipment with Merit Review funded projects in which the principal investigator is actively involved (data accumulation and analysis, literature review and manuscripts writing). The principal Investigator uses an entirely separate microscopy and recording unit for data collection. The Principal Investigator introduced the concept of treating hemorrhagic shock with osmotic stress, which is the substance of this current research proposal.

 

“In Vivo Study of Interstitial Convection”

Principal Investigator:  Michael F. Flessner, MD, PhD

Agency: National Institute of Diabetes, Digestive, and Kidney Diseases

Type: R29 (DK 48479, Year 1-5)   Period: June 01, 1995 to May 31, 2000.

Role: Data collection and analysis, literature search and manuscripts preparation.

The long-term goal of this project was the quantitative study of movement of protein and fluid through the tissue interstitium. A detailed mathematical model was formulated to simulate diffusion, convection, capillary exchange, lymphatic removal, and binding of protein in tissue.  In vivo experiments were carried out in a unique animal preparation: the rat abdominal wall during peritoneal dialysis. Parameters such as tissue diffusivity, tissue hydraulic conductivity, extracellular volume, and volume available to protein have been determined as functions of interstitial pressure.   To produce a predictive tool of interstitial convection, the mathematical model was fitted to tissue concentration profiles measured with quantitative autoradiography.

 

“Limiting Factors in the Peritoneal-Blood Transport of Water and Solutes”

Principal Investigator: Michael F. Flessner, MD, PhD

Agency: American Heart Association

Type: Grant-in-Aid Jan 1, 1997-Dec 31, 1999.

Role: Data collection and analysis, literature search and manuscripts preparation.

 

The hypotheses addressed in this study are that blood flow to the subperitoneal tissue does not limit transport and that the entire surface of the peritoneum is not in contact with a large volume of the solution in the cavity.  Using a unique combination of techniques, including Laser-Doppler flowmetry, diffusion chambers affixed directly to the peritoneum, and quantitative autoradiography, we have demonstrated: a) that all peritoneal tissues are sources of osmotically-induced volume flow into the peritoneal cavity, b) that local blood flow reductions of 50-80% do not significantly affect volume or solute transport across the peritoneum, and c) that only 35-45% of the peritoneal surface is in contact with the peritoneal fluid at any one time. To determine microcirculatory coefficients of tissue diffusivity and capillary permeability-area, we have successfully combined mathematical modeling with mass transfer data from diffusion chambers and with the solute concentration profiles in the tissue below the chamber.

 

ONGOING RESEARCH PROJECTS:

Active

R01 (Zakaria & Garrison)                                   04/01/2004 – 03/31/2008,

NIH (RFA# HL+03-015)

        

“Direct Peritoneal Resuscitation from Hypovolemic Shock.”     $700,000

Role: Co-principal Investigator

 

The major goals of this project are to utilize the concept of clinical peritoneal dialysis as a new innovative technique of direct peritoneal resuscitation from hemorrhagic shock, and to identify the mechanisms by which this new technique can reverse the pathophysiology of hemorrhagic shock, and hence prevention of tissue injury and multisystem organ failure.

 

 

Garrison (Merit Review, RNG-004)                              04/01 – 03/06           

                  Department ofVeterans Affairs Merit Review              $678,500                       

“Microcirculation During Systemic Sepsis”

                  Role: Co-Investigator.

 

The major goals of this project are to investigate the microcirculatory events in skeletal and intestinal microvascular beds during chronic sepsis, with an emphasis on local microvascular control mechanisms, and the effect of systemic inflammation on these control mechanisms.

 

Grant-In-Aid #0255459B (Garrison)                   7/1/2002 – 6/30/2004           5%

Ohio Valley Affiliate (AHA)                            $107,443                       

“Role of Adenosine in Postprandial Hyperemia.”

Role: Co-Investigator.

 

 

The major goals of this project are to study the basic mechanisms of post-prandial hyperemia, or increased blood flow to the gastrointestinal tract during nutrient absorption. Energy-dependent glucose transport into the cellular compartment is thought to be one of the two major mechanisms responsible for hypertonic glucose solution-mediated vascular reactivity. This will be addressed in our current grant proposal.

 

 

 

                 “Quality and availability of brain-dead organ allographs can be secured by direct peritoneal resuscitation (DPR) using conventional peritoneal dialysis solutions”.

                    Agency: Mason-Rod.

                 Role: Co-PI                                               $ 150,000

 

The major goal of this project is to improve the quality and availability of organs harvested from brain-dead organ donors. This is achieved by treating of brain-dead organ donors by peritoneal dialysis prior to organ harvesting.

 

 

Overlap

Many of the techniques and data analysis used for the three active grants are similar. There is no fiscal overlap between the proposals but common core facilities and equipment were shared along with co-PI dialogue.

 

Pending:

                 

“Mechanisms of Hyperosmolality-Induced Vascular Reactivity.”

Agency: NIH, RO1

Role: Principal Investigator.                                   $ 800,000

 

The major goals of this project are to study the molecular mechanisms of clinical peritoneal dialysis-mediated vascular reactivity, and to solve the disparity in vascular reactivity between the microcirculation and large vessels when exposed to hyperosmolality.

 

 

                     “Interstitial Factors in Shock-induced Tissue Injury”.

                      Agency:Shock Society/Novo Nordisk.

                  Role: Principal Investigator.                                   $ 120,000

 

The major goal of this project is to investigate the role of the interstitial matrix macromolecular component hyaluronan and its receptor CD44 in the pathogenesis of distant organ injury following conventional resuscitation from hemorrhagic shock.

 

 

                     “Direct Intracellular Energy Delivery in Shock”.

Agency: NIH, SBIR: TECHNOLOGIES FOR MONITORING AND PERFORMING RESUSCITATION.

         Role: Principal Investigator.                                   $ 300,000 

 

The major goal of this project is to restore cellular energy by direct intracellular delivery of high energy charge (ATP) directly into the cytosol by VitaSol™ with a final goal of reversing the overall pathophysiology of hemorrhage-induced cellular dysfunction.

 

Pre-proposals:

“Early intracellular energy delivery and delayed direct peritoneal resuscitation from hemorrhagic shock”.

Agency: NIH and The United States Army Medical Research and Material Command”. (A phase I clinical trial).

Role: Principal Investigator                           

 

The goal of this basic science project is to combine direct intracellular energy delivery with VitaSol and peritoneal dialysis as a technique of direct peritoneal resuscitation (DPR) as adjunctive therapy from trauma and hemorrhagic shock.

 

 

 

“Direct peritoneal resuscitation from hemorrhagic shock”

Agency: NIH and the United States Army Medical Research and Material Command”. (A phase I clinical trial).

Role: Co-Principal Investigator                      

 

The goal of this phase I clinical trial is to adopt peritoneal dialysis as a technique of direct peritoneal resuscitation (DPR) from trauma and hemorrhagic shock.