Carbon monoxide inhibition of regulatory pathways in myocardium.
The 1H nuclear magnetic resonance (NMR) myoglobin (Mb) Val E11 signal provides a unique opportunity to assess the functional role of Mb in the cell. On CO infusion in perfused myocardium, the MbO2 signal at -2.76 parts per million (ppm) gradually disappears, whereas the corresponding MbCO signal emerges at -2.26 ppm, reflecting the state of Mb inhibition. Up to 76.8% MbCO saturation, myocardial O2 consumption (MVO2) remains constant, whereas the rate-pressure product (RPP) has already dropped to 92% of the control level. At 87.6% MbCO saturation, the lactate formation rate has increased by a factor of two, and MVO2 begins to decline. However, the ratio CO/O2 is still 1/10, well below the inhibition threshold for cytochrome oxidase activity. The MVO2 decline in the face of an adequate O2 supply and an unperturbed high-energy phosphate level implies that Mb may play a role in directly regulating respiration, mediated potentially by a shift in NADH/NAD. Although nitrite inhibits Mb, nitrite also directly affects the myocardial function.
Glabe
A
A
Department of Biological Chemistry, University of California, Davis, California 95616-8635, USA.
Chung
Y
Y
Xu
D
D
Jue
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009211:Myoglobin; D009573:Nitrites; D010725:Phosphocreatine; D010758:Phosphorus; D019344:Lactic Acid; D002248:Carbon Monoxide; D000255:Adenosine Triphosphate