Carbon monoxide inhibition of regulatory pathways in myocardium

The 1H nuclear magnetic resonance (NMR) myoglobin (Mb) Val Ell signal provides a unique opportunity to assess the functional role of Mb in the cell. On CO infusion in perfused myocardium, the MbO(2) 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 O-2 consumption (M(V) over doto(2)) 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 MVo(2) begins to decline. However, the ratio CO/O-2 is still 1/10, well below the inhibition threshold for cytochrome oxidase activity. The MVo(2) decline in the face of an adequate O-2 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.