ROBERT W WINSLOW

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi Blood substitutes
    Robert M Winslow
    Sangart, Inc, San Diego, California 92121, USA
    Curr Opin Hematol 9:146-51. 2002
  2. ncbi Red cell substitutes
    Robert M Winslow
    Sangart, Inc, and Department of Bioengineering, University of California, San Diego, CA 92121, USA
    Semin Hematol 44:51-9. 2007
  3. ncbi MP4, a new nonvasoactive polyethylene glycol-hemoglobin conjugate
    Robert M Winslow
    Sangart, Inc, San Diego, CA 92121, USA
    Artif Organs 28:800-6. 2004
  4. ncbi Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat
    Robert M Winslow
    Sangart, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92121, USA
    J Appl Physiol 97:1527-34. 2004
  5. ncbi Current status of oxygen carriers ('blood substitutes'): 2006
    R M Winslow
    Sangart, Inc, San Diego, USA
    Vox Sang 91:102-10. 2006
  6. ncbi Alternative oxygen therapeutics: products, status of clinical trials, and future prospects
    Robert M Winslow
    Sangart, Inc, 11189 Sorrento Valley Road, Suite 104, San Diego, CA 92121, USA
    Curr Hematol Rep 2:503-10. 2003
  7. ncbi The role of hemoglobin oxygen affinity in oxygen transport at high altitude
    Robert M Winslow
    Sangart Inc, San Diego, CA 92121, United States
    Respir Physiol Neurobiol 158:121-7. 2007
  8. ncbi Red cell age and loss of function: advance or SNO-job?
    Robert M Winslow
    Department of Bioengineering, University of California, San Diego, CA, USA
    Transfusion 48:411-4. 2008
  9. ncbi Current status of blood substitute research: towards a new paradigm
    R M Winslow
    Sangart, Inc, San Diego, CA 92121, USA
    J Intern Med 253:508-17. 2003
  10. doi Cell-free oxygen carriers: scientific foundations, clinical development, and new directions
    Robert M Winslow
    Sangart Inc, San Diego, California, USA
    Biochim Biophys Acta 1784:1382-6. 2008

Research Grants

Collaborators

Detail Information

Publications35

  1. ncbi Blood substitutes
    Robert M Winslow
    Sangart, Inc, San Diego, California 92121, USA
    Curr Opin Hematol 9:146-51. 2002
    ..Comparison of oxygen carriers with more traditional starch-based products provides new insight into the interaction of oxygen transport, microvascular perfusion, and blood volume expansion...
  2. ncbi Red cell substitutes
    Robert M Winslow
    Sangart, Inc, and Department of Bioengineering, University of California, San Diego, CA 92121, USA
    Semin Hematol 44:51-9. 2007
    ..After more than a century of research, one of these new solutions should find use as an alternative to red cells for transfusion in certain clinical settings...
  3. ncbi MP4, a new nonvasoactive polyethylene glycol-hemoglobin conjugate
    Robert M Winslow
    Sangart, Inc, San Diego, CA 92121, USA
    Artif Organs 28:800-6. 2004
    ..Preservation of functional capillary density and prevention of vasoconstriction further contribute to the effectiveness of this new formulation. MP4 is currently being tested in humans...
  4. ncbi Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat
    Robert M Winslow
    Sangart, 11189 Sorrento Valley Rd, Suite 104, San Diego, CA 92121, USA
    J Appl Physiol 97:1527-34. 2004
    ..We conclude that, despite its low PO2 necessary to obtain 50% O2, MP4 effectively substitutes for red blood cell hemoglobin in its ability to oxygenate tissues in extreme hemodilution...
  5. ncbi Current status of oxygen carriers ('blood substitutes'): 2006
    R M Winslow
    Sangart, Inc, San Diego, USA
    Vox Sang 91:102-10. 2006
    ..Such products may seem counterintuitive by traditional standards, but it is hoped that they will be less toxic, more beneficial to patients, and more economical to produce...
  6. ncbi Alternative oxygen therapeutics: products, status of clinical trials, and future prospects
    Robert M Winslow
    Sangart, Inc, 11189 Sorrento Valley Road, Suite 104, San Diego, CA 92121, USA
    Curr Hematol Rep 2:503-10. 2003
    ..It is possible that one or more of the earlier products may be approved by regulatory agencies in 1 or 2 years. However, a universally compatible and safe product most likely will be unavailable for several more years...
  7. ncbi The role of hemoglobin oxygen affinity in oxygen transport at high altitude
    Robert M Winslow
    Sangart Inc, San Diego, CA 92121, United States
    Respir Physiol Neurobiol 158:121-7. 2007
    ....
  8. ncbi Red cell age and loss of function: advance or SNO-job?
    Robert M Winslow
    Department of Bioengineering, University of California, San Diego, CA, USA
    Transfusion 48:411-4. 2008
  9. ncbi Current status of blood substitute research: towards a new paradigm
    R M Winslow
    Sangart, Inc, San Diego, CA 92121, USA
    J Intern Med 253:508-17. 2003
    ..These include increased O2 affinity (low P50) and increased viscosity and oncotic pressure. These second-generation solutions hold greater promise for clinical development...
  10. doi Cell-free oxygen carriers: scientific foundations, clinical development, and new directions
    Robert M Winslow
    Sangart Inc, San Diego, California, USA
    Biochim Biophys Acta 1784:1382-6. 2008
    ..Because of its low P50 and increased molecular size, the release of O2 in resistance vessels (arterioles) by Hemospan is restricted, and vasoconstriction is greatly reduced...
  11. ncbi Targeted O2 delivery by low-p50 hemoglobin: a new basis for hemoglobin-based oxygen carriers
    Robert M Winslow
    Sangart, Inc, San Diego, CA 92121, USA
    Artif Cells Blood Substit Immobil Biotechnol 33:1-12. 2005
    ..Preservation of functional capillary density and prevention of vasoconstriction further contribute to the effectiveness of this new formulation...
  12. ncbi MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine
    Mark A Young
    Sangart, San Diego, CA, USA
    Crit Care Med 33:1794-804. 2005
    ..This study evaluated resuscitation with MP4 in anesthetized swine hemorrhaged 250 mL by controlled withdrawal, followed by a 5-mm tear in the abdominal aorta...
  13. ncbi Effects of extreme hemodilution with hemoglobin-based O2 carriers on microvascular pressure
    Pedro Cabrales
    Department of Bioengineering, University of California San Diego, La Jolla, CA 92093 0412, USA
    Am J Physiol Heart Circ Physiol 288:H2146-53. 2005
    ..Microvascular resistance in arterioles with a diameter range of 70-80 microm showed an increase relative to control with alpha alpha Hb, whereas MP4 caused a decrease...
  14. pmc A quantitative framework for the design of acellular hemoglobins as blood substitutes: implications of dynamic flow conditions
    Russell H Cole
    Department of Mechanical Engineering, 140 Hesse Hall, University of California, Berkeley, CA 94720, USA
    Biophys Chem 128:63-74. 2007
    ..The model predicts that regardless of size, hemoglobin solutions with higher p50 will present excess O(2) to arteriolar walls. Oversupply of O(2) to arteriolar walls may cause constriction and paradoxically reduced capillary perfusion...
  15. pmc Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers
    Amy G Tsai
    Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093 0412, USA
    Blood 108:3603-10. 2006
    ....
  16. ncbi MP4, a new nonvasoactive PEG-Hb conjugate
    Kim D Vandegriff
    Sangart, Inc, 11189 Sorrento Valley Road, Suite 104, San Diego, CA 92121, USA
    Transfusion 43:509-16. 2003
    ..Vasoconstriction has been an obstacle to clinical development of Hb-based O2 carriers. It is proposed that this limitation can be overcome by increasing molecular size and oxygen affinity...
  17. ncbi Targeted O2 delivery by low-P50 hemoglobin: a new basis for O2 therapeutics
    Amy G Tsai
    Department of Bioeengineering, University of California, San Diego, La Jolla 92023, USA
    Am J Physiol Heart Circ Physiol 285:H1411-9. 2003
    ..Higher O2 extraction of both red blood cell and plasma hemoglobin in capillaries represents a new mechanism of action of cell-free hemoglobin. High O2 affinity appears to be an important property for cell-free hemoglobin solutions...
  18. ncbi Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys
    Mark A Young
    Sangart, Inc, San Diego, CA 92121, USA
    Transl Res 149:333-42. 2007
    ..These results demonstrate that MP4 is safe and is without hemodynamic effects when administered as an exchange transfusion of 30% of estimated blood volume...
  19. doi Effect of maleimide-polyethylene glycol hemoglobin (MP4) on hemodynamics and acid-base status after uncontrolled hemorrhage in anesthetized swine: comparison with crystalloid and blood
    Mark A Young
    Sangart, Inc San Diego, CA, USA
    J Trauma 63:1234-44. 2007
    ..This study evaluated resuscitation with MP4 after uncontrolled hemorrhage in anesthetized swine, and compared the effects of MP4 alone with those of standard-of-care crystalloid or crystalloid + blood...
  20. ncbi Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters
    Reto Wettstein
    Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0412, USA
    Crit Care Med 31:1824-30. 2003
    ..5 cP, colloid osmotic pressure of 49 mm Hg, and p50 of 5.5 mm Hg, improves systemic and microvascular variables after hemorrhage compared with shed blood (SB) and 5% hydroxyethyl starch (HES)...
  21. doi Sites of modification of hemospan, a poly(ethylene glycol)-modified human hemoglobin for use as an oxygen therapeutic
    Kim D Vandegriff
    Sangart Inc, San Diego, California 92121, USA
    Bioconjug Chem 19:2163-70. 2008
    ....
  22. doi Hemospan improves outcome in a model of perioperative hemodilution and blood loss in the rat: comparison with hydroxyethyl starch
    Mark A Young
    Sangart Inc, San Diego, CA 92121, USA
    J Cardiothorac Vasc Anesth 23:339-47. 2009
    ..MP4 was compared with hydroxyethyl starch solutions of differing concentrations (ie, HES 260/0.45 and HES 130/0.4)...
  23. doi Hemospan: design principles for a new class of oxygen therapeutic
    Kim D Vandegriff
    Sangart, Inc, San Diego, CA, USA
    Artif Organs 33:133-8. 2009
    ..Phase III trials in orthopedic surgery have recently completed enrollment in Europe...
  24. ncbi Resuscitation from hemorrhagic shock with MalPEG-albumin: comparison with MalPEG-hemoglobin
    Reto Wettstein
    Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093 0412 USA
    Shock 22:351-7. 2004
    ..7 cP (vs. 2.5 cP for MalPEG-Hb). The present results show that both solutions are efficacious plasma expanders and that the hemoglobin-based solution provides improved oxygen distribution and tissue Po2 in the hamster chamber model...
  25. pmc Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates
    Kim D Vandegriff
    Sangart, Inc, 6175 Lusk Blvd, San Diego, California 92121 USA
    Biochem J 399:463-71. 2006
    ....
  26. pmc Kinetics of NO and O2 binding to a maleimide poly(ethylene glycol)-conjugated human haemoglobin
    Kim D Vandegriff
    Sangart Inc, 11189 Sorrento Valley Rd, Ste 104, San Diego, CA 92121, USA
    Biochem J 382:183-9. 2004
    ..Alternatively, the unique O2-binding characteristics with low p50 and co-operativity suggest that the 'R-state' conformation of MalPEG-Hb is in a more T-state configuration and restricted from conformational change...
  27. ncbi Microvascular oxygen distribution in awake hamster window chamber model during hyperoxia
    Amy G Tsai
    Department of Bioengineering, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0412, USA
    Am J Physiol Heart Circ Physiol 285:H1537-45. 2003
    ....
  28. ncbi A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol
    Magnus Bjorkholm
    Karolinska Hospital and Institute, Stockholm, Sweden
    Haematologica 90:505-15. 2005
    ..A phase I clinical trial of MP4 was undertaken to evaluate whether MP4 elicits the clinical side effects associated with previous hemoglobin-based solutions...
  29. ncbi Extreme hemodilution with PEG-hemoglobin vs. PEG-albumin
    Pedro Cabrales
    La Jolla Bioengineering Institute, 505 Coast Blvd S, Suite 405, La Jolla, CA 92037, USA
    Am J Physiol Heart Circ Physiol 289:H2392-400. 2005
    ..MP4 was significantly higher than MPA (P < 0.05) and was not statistically different from baseline, an effect due to the additional oxygen release to the tissue by the Hb MP4...
  30. pmc Solution structure of poly(ethylene) glycol-conjugated hemoglobin revealed by small-angle X-ray scattering: implications for a new oxygen therapeutic
    Dmitri I Svergun
    European Molecular Biology Laboratory, Hamburg Outstation, Hamburg, Germany
    Biophys J 94:173-81. 2008
    ..The proposed methodology for assessment of low-resolution structures and interactions is a powerful means for rational design of PEGylated therapeutic agents...
  31. ncbi Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive
    Seetharama A Acharya
    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
    Artif Cells Blood Substit Immobil Biotechnol 33:239-55. 2005
    ..The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported...
  32. ncbi Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4)
    Dan Drobin
    Department of Anesthesiology, Karolinska Institute at Soder Hospital, S 118 83 Stockholm, Sweden
    J Appl Physiol 96:1843-53. 2004
    ....
  33. ncbi A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery
    Christina Olofsson
    Karolinska University Hospital, Solna, Stockholm, Sweden
    Anesthesiology 105:1153-63. 2006
    ..Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia...
  34. ncbi To publish or not to publish
    Robert M Winslow
    J Lab Clin Med 145:221; discussion 222. 2005
  35. doi Hemoglobin-based blood substitutes and risk of myocardial infarction and death
    Peter E Keipert
    JAMA 300:1295-6; author reply 1298-9. 2008

Research Grants4

  1. Oxygen Carriers for Hypovolemic Circulatory Collapse
    Robert Winslow; Fiscal Year: 2007
    ..The research described in this proposal will focus on molecules and formulations specifically tailored for use in prehospital and trauma settings. ..