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Carbon monoxide as a modulator of myocardial function

Institution: University of California, Davis
Investigator(s): Ulrike Kreutzer, Ph.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8KT-0042 Award: $225,000
Subject Area: Cardiovascular Disease
Award Type: New Investigator Awards
Abstracts

Initial Award Abstract
Subjects exposed to environmental tobacco smoke (ETS) inhale the poisonous gas, carbon monoxide (CO). Because CO readily displaces oxiygen in blood, it can inhibit the oxygen delivery to the tissue. Indeed many researchers have found that the levels of CO found in ETS can significantly increase the risk of heart disease and can reduce the capacity to perform strenuous exercise in persons with preexisting heart conditions.

However, the toxic effect of CO is not restricted solely to its capacity to block oxygen delivery. Some researchers believe that CO can directly inhibit cellular function. In particular, CO can also bind with a high affinity to the intracellular oxygen storage protein, myoglobin. In effect, CO can impair oxygen delivery to the cell and oxygen availability within the cell. Myoglobin inhibition can then aggravate the deleterious effects of ETS on heart function.

To understand how CO inhibition of myoglobin can impair heart cells, we must understand more precisely how myoglobin actually functions in vivo. The proposed study will determine to what extent myoglobin contributes to oxygen transport within the cell during the normal state as well as during increased oxygen demand or diminished blood flow. Furthermore the study will explore whether CO inhibition of myoglobin can directly impact cellular respiration. The results will lead to a better understanding on how CO in ETS can impair respiratory and heart function.
Publications

Role of myoglobin as a scavenger of cellular no.
Periodical: International Society of Magnetic Resonance in Medicine Index Medicus:
Authors: Kreutzer U, Jue T ABS
Yr: 2002 Vol: 10 Nbr: Abs: Pg: 1708

Role of myoglobin as a scavenger or NO in rat myocardium
Periodical: FASEB Journal Index Medicus:
Authors: Jue T, Kreutzer U, Chung Y ABS
Yr: 2003 Vol: 17 Nbr: Abs: Pg: A1251