PHA/ATS Partnership Grant Winner 2007
Arlin Brice Blood, Ph.D.
Loma Linda University School of Medicine
“The Interaction of Nitric Oxide and Hemoglobin in Regulation of Pulmonary Vascular Tone”
Term: January 1, 2007 – December 31, 2008
Summary of Research Project:
The Interaction of Nitric Oxide and Hemoglobin in Regulation of Pulmonary Vascular Tone
Pulmonary hypertension is a disease in which blood pressure between the heart and the lung is elevated, sometimes due to constriction of the arteries carrying blood to the lung. In severe cases, pulmonary hypertension can lead to impaired blood flow to the lungs and an inability to adequately oxygenate the blood. In addition, the additional work required by the heart to pump blood through the lung can lead to heart disease and failure.
Hemolysis is a condition in which red blood cells (rbcs) in the blood break open, spilling their contents into the plasma. By far the main content of rbcs is hemoglobin, the protein responsible for carrying oxygen in the blood. In severe hemolysis, the ability of the body to clear hemoglobin from the plasma is overwhelmed. When this happens, hemoglobin in the plasma becomes a toxin.
The primary toxic effect of free plasma hemoglobin is its tendency to bind quickly to an important chemical in the blood called nitric oxide (NO). NO is produced by the body and is necessary in order to relax the arteries, which keeps blood pressure low. When hemoglobin is free in the plasma, it scavenges NO in the circulation, resulting in artery contraction and increased blood pressure. Recent evidence indicates that free hemoglobin selectively constricts pulmonary arteries, leading to pulmonary hypertension. The studies proposed in this application will develop an animal model of pulmonary hypertension cause by hemolysis and then use that model to explore the mechanisms and potential treatments of this disease.
2003 Loma Linda University
Loma Linda, CA
(Minor in Asian Studies, Biology, and Chemistry)
1994 University of Nebraska
Loma Linda University School of Medicine
Dec 2005 - Present
Department of Pediatrics
Department of Physiology and Pharmacology
Radiant Research, Honolulu
July 2003 - Nov 2005
Nov 2005 - Present
Loma Linda University
Jun 2003 - Nov 2005
Loma Linda, CA
Aug 2000 - Jun 2003
Research Fellow Research Associate, PhD student
MDS Pharma Services
Lincoln, NE and Phoenix, AZ
Mar 1999 - Jan 2001
Clinical Conduct Consultant
May 1997- Mar 1999
Phoenix Clinical Operations Manager
Jun 1996 - May 1997
Clinical Study Manager
Jan 1995 - June 1996
Clinical Conduct Specialist and Technician
- American Association of Pharmaceutical Scientists, 2001
- American Physiological Society, 2002
- Fetal and Neonatal Physiological Society, 2001
- Drug Information Association, 2004
- American College of Clinical Pharmacologists, 2005
- Affiliate Member of the Center for Perinatal Biology, Loma Linda University School of Medicine, 2006
Specific Skills and Languages
- Some Mandarin Chinese
- Proficient in Microsoft Excel, Word, Powerpoint, Microsoft (’98 and XP) and Apple (9.x and X) operating systems, Graphpad Prism, Matlab, Biopac Acqknowledge, ADI Chart, ScOP, STELLA, and Adobe Illustrator, Photoshop, Acrobat, InDesign, and others.
- Basic familiarity with UNIX/LINUX
Honors and Awards
- 2001 American Physiology Society Travel Award
- 2001 Western Student Medical Research Committee Student Research Award
- 2001 Annual Postgraduate Convention Graduate Student Research Award
Other Published Articles
- Power GG, Blood AB, and Hunter CJ. Perinatal thermal physiology. Fetal and Neonatal Physiology. Polin, Fox, and Abman 3rd edition. p541-547, 2004
- Blood AB, Power GG. Perinatal thermal physiology. Fetal and Neonatal Physiology. Polin, Fox, and Abman 4th edition. In submission, 2006
Manuscripts in Peer Reviewed Journals
- Blood AB, Zhao Y, Long W, Zhang L, Longo LD. L-type Ca2+ channels in fetal and adult ovine cerebral arteries. Am J Physiol Regul Integr Comp Physiol. 2002 Jan;282(1):R131-8.
- Blood AB, Hunter CJ, and Power GG. The role of adenosine in the control of cerebral blood flow during hypoxia in the late term ovine fetus. J. Physiol. 2002 Sep;543(3):1015-1023.
- Bishai JM, Blood AB, Hunter CJ, Longo LL, and Power GG. Comparison of Fluorescent microsphere and laser Doppler flowmetry techniques form the measurement for cerebral blood flow in the fetal sheep. J. Physiol. 2003 Feb 1;546(Pt 3):869-78.
- Hunter CJ, Blood AB, and Power GG. The role of nitric oxide in the control of cerebral blood flow during hypoxia in the late term ovine fetus. J Physiol. 2003 Jun 1;549(Pt 2):625-33.
- Blood AB, Chihara H, Hunter CJ, Power GG. The effect of hypothermia on fetal cerebral blood flow and metabolic rate. Pediatr Res. 2003 Jul 16
- Hunter CJ, Blood AB, and Power GG. Cerebral metabolism during cord occlusion and hypoxia in the fetal sheep: a novel method of continuous measurement based on heat production. J. Physiol. 2003 Jul 23
- Lotgering FK, Bishai JM, Blood AB, Hunter, CJ, Power GG, Longo LD. Ten-minute umbilical cord occlusion markedly reduces cerebral blood flow and heat production in fetal sheep. Am J Obstet Gynecol. 2003 Jul;189(1):233-8
- Hunter CJ, Bennet L, Power GG, Roelfsema V, Blood AB, Quaedackers JS, Guan J, and Gunn AJ. A key neuroprotective role for endogenous adenosine A1 receptor activation during asphyxia in the fetal sheep. Stroke 2003 Sep;34(9):2240-5. Epub 2003 Aug 21
- Blood AB, Hunter CJ, and Power GG. Adenosine mediates decreased cerebral metabolic rate and increased cerebral blood flow during acute moderate hypoxia in the near-term fetal sheep J Physiol. 2003 Dec 15;553(Pt 3):935-45. Epub 2003 Sep 18.
- Lotgering FK, Bishai JM, Blood AB, Hunter CJ, Oberg KC, Power GG, Longo LD. Absence of robust ischemic preconditioning by five 1-min total cord occlusions in fetal sheep. J SOC. GYNECOL. INVESTIG. 2004 OCT; 11(7): 449-56
- Hunter CJ, Blood AB, Wall, DD, Power GG, Hopper AO. Cerebral blood flow is decreased during venoarterial but not venovenous ECMO in newborn lambs. Pediatr. Crit. Care Med. 2004 SEP; 5(5):475-81.
- Hunter CJ, Dejam A, Blood AB, Machado RF, Tarekegn S, Hopper AO, Schechter AN, Power GG, Gladwin MT. Therapeutic application of nebulized nitrite as a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med. 2004 OCT;10(10):1122-1127.
- Nishida N, Blood AB, Hunter CJ, Bragg S, Pearce WJ, Power GG. The role of prostanoids in the regulation of fetal cerebral blood flow during hypoxia. Ped Res. 2006. In Press.
- Blood AB, Power GG. In vitro and in vivo kinetic handling of nitrite in blood: effects of varying hemoglobin oxygen saturation. Am J Physiol Heart and Circ Physiol. In revision.
- Vuong LT, Ruckle JR, Blood AB, Reid MR, Wasnich RD, Dueker SD. Re-evaluation of pharmacokinetics of zidovudine by human microdosing and accelerator mass spectrometry – an effective approach for the development and testing of antiretroviral therapies. Antimicrob Agents Chemo. Under review.
Selected Original Presentations
- Blood AB. The role of microdosing in early-phase clinical research. BioJapan 2005. Sept, 2005.
- Blood AB, Hunter CJ, Hickerson A, Bishai JM, Peverini R, Power GG, Hopper AH. The effect of VA and VV ECMO on cerebral autoregulation and blood flow responses to hypoxia in the newborn lamb. Society for Pediatric Research. May, 2003.
- Blood AB, Hunter CJ, Power GG. Adenosine mediates cerebral blood flow and metabolic rate in the fetal sheep during hypoxia. Society for Gynecologic Investigation. March, 2003.
- Blood AB. The role of adenosine in regulation of fetal sheep cerebral blood flow and metabolism. Loma Linda University School of Medicine, Center for Perinatal Biology, October, 2002
- Blood AB. The effect of inhaled L-arginine on pulmonary vasculature of the newborn lamb. Pediatric Grand Rounds. Loma Linda University School of Medicine. July, 2002
- Blood AB, Hunter CJ, Hickerson A, Power GG, Job L. The effect of inhaled L-arginine on pulmonary vasculature of the newborn lamb. Society for Pediatric Research. May 2002
- Blood AB, Zhao J, Long W, Zhang L, Longo LD. L-type Ca2+ channels in fetal and adult ovine cerebral arteries. Fetal and Neonatal Physiologic Society. August 2001
- Blood AB, Zhao J, Long W, Zhang L, Longo LD. L-type Ca2+ channels in fetal and adult ovine cerebral arteries. International Union of Physiology Society. August 2001
- Blood AB, Hunter CJ, Power, GG. Adenosine mediates hypoxic increases in cerebral blood flow in the fetal sheep. Fetal and Neonatal Physiologic Society. August 2001
- Blood AB, Hunter CJ, Power, GG. Adenosine mediates hypoxic increases in cerebral blood flow in the fetal sheep. International Union of Physiology Society. August 2001
- Blood AB, Hunter CJ, Power, GG. Adenosine mediates hypoxic increases in cerebral blood flow in the fetal sheep. Western Student Medical Research. March 2001