Logo: University of Southern California

Biomedical Team to Participate in New $2.4 Million NIH Study

BME Department Chair Michael Khoo and graduate student will study autonomic nervous system abnormalities in patients with sickle cell anemia

August 08, 2008 — Viterbi School biomedical engineering professor and department chair Michael Khoo, who specializes in cardio-neuro-respiratory systems modeling and non-invasive physiological monitoring, will participate in a new $2.4 million multidisciplinary study funded by the National Institutes of Health (NIH) to investigate the impact of blood viscosity on oxygen delivery in people with sickle cell anemia.
Sickle Cell 1
NIH team, from left: Michael Khoo, Thomas Coates, Herbert Meiselman, John Wood and Tamas Alexy at Childrens Hospital Los Angeles.

Khoo, holder of the Dwight C. and Hildegard E. Baum Chair, and graduate student Suvimol Sangkatumvong, who works in the Cardiorespiratory Sleep Laboratory at USC, will join a team of physicians and faculty from Childrens Hospital Los Angeles and the Keck School of Medicine of USC to understand the principles that regulate blood flow in patients with this genetic disorder.  The study will be led by principal investigator Thomas D. Coates, professor of pediatrics and pathology at the Keck School of Medicine of USC.

“There is a lot we don’t understand about sickle cell disease, but we suspect that there is something abnormal going on in the autonomic nervous system that facilitates or triggers these episodes of ‘sickling,’” said Khoo.  “When sickling occurs, normally flexible red blood cells are transformed into rigid, sickle-shaped cells and often become blocked when they try to pass through small blood vessels.”

People with sickle cell disease make a different form of hemoglobin A, which carries oxygen to tissues throughout the body.  The abnormal hemoglobin is called hemoglobin S, for sickle cell. This abnormal hemoglobin does not live as long as hemoglobin A and leads to low red blood cell counts, or anemia.

Researchers believe that the sickling process can also be triggered by exposure to certain conditions, such as hypoxia, a shortage of oxygen in the blood that can occur naturally during sleep.  Sickle cell anemia patients are hypersensitive to breathing disorders like sleep apnea, said Khoo, who has studied the disorder for many years.

Sickle cell patients often suffer throughout their lifetimes from mild to acute pain chest pain, multi-organ dysfunction, stroke and renal dysfunction caused by reduced oxygenation of tissues. They are also at greater risk of dying suddenly of cardiac arrest from a vascular occlusive crisis in which the blood flow to vital organs is blocked.

The USC team will break into two groups to study the disease. Herbert Meiselman, professor of physiology and biophysics at Keck, will head up one team making blood viscosity measurements. Khoo will head up another team monitoring subjects' autonomic nervous systems.
Suvimol Sangkatumvong, a third year biomedical engineering graduate student, conducts data analysis at Childrens Hospital Los Angeles, where the study is being conducted.

The researchers will expose two groups of subjects — one a normal control group and the other a sickle cell group — to brief episodes of artificially induced hypoxia, which can be induced by inhaling small amounts of pure nitrogen, said Sangkatumvong.

She and Khoo will make measuremensts of each subject's autonomic system during hypoxia using a non-invasive Lifeshirt™ physiological monitoring system wrapped around the chest.   Lifeshirt™ will be able to measure heart rate variability and other autonomic system functions, such as blood pressure and body temperature.  Khoo and Sangkatumvong will then analyze changes in autonomic activity using a computer model of cardiovascular autonomic control.

Coates said the preclinical trial will be conducted at Childrens Hospital Los Angeles, which supports the only sickle cell basic and translational research program on the West Coast.  He is section head of  hematology and director of the Red Cell Defects Program in the Childrens Center for Cancer and Blood Diseases at the hospital.  

“This work follows up on previous work we have done," explained Sangkatumvong.  "We have found in initial studies that autonomic nervous system reactivity in sickle cell patients is different from people without the disorder, and that this may be used as a possible means of predicting future crises.

“However, right now there is no available technique that can reliably distinguish the cause or predict the occurrence of a vascular occlusion," she said. "The sickling process seems to occur continually in subjects with sickle cell anemia, resulting in a cardiovascular crisis of some sort.”

Other faculty on the project include John Wood, associate professor of pediatrics and radiology at Childrens Hospital, and Tamas Alexy, assistant professor of research in physiology and biophysics at the Keck School of Medicine of USC.

The study continues a longstanding relationship between the Hemoglobinopathy Program at Childrens Hospital Los Angeles and its research counterparts at USC.