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Carbon Monoxide Transport and Actions in Blood and Tissues

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This chapter will discuss the transport of carbon monoxide (CO) from the environment to the tissues of the body and physiological effects on blood‐borne cells and perivascular tissues. It will review the physiology of CO exchange between alveolar gas and pulmonary capillary blood, dynamics of hemoglobin transport, the effects of CO on blood elements, and the effects of CO on extravascular tissues at the capillary bed. Effects of CO from exogenous and endogenous sources on the activities of different proteins will be reviewed. Because CO binds competitively to heme‐containing proteins its effects depend on CO concentration relative to alternative ligands. Therefore, some discussion is devoted to how nitric oxide and hydrogen sulfide influence CO effects. © 2011 American Physiological Society. Compr Physiol 1:421‐446, 2011.

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Figure 1. Figure 1.

Schematic depicting interactions between carbon monoxide (CO)/heme oxygenase‐1, and nitric oxide/nitric oxide synthase (NO/NOS). CO generated by HO‐1 can mediate HO‐1 and NOS synthesis in pathways involving several transcription factors (TF's) 76,155,172,193,225,389. HO‐1 synthesis can also be induced by NO (shown with the label “mRNA”), although the mechanism for gene regulation has not been elucidated 50,51,234,244,245. The figure also indicates that CO can inhibit NOS activity, although local concentrations of enzyme substrates and co‐factors have a large impact on CO affinity 1,25,94,192,288,315,381.

Figure 2. Figure 2.

Oxyhemoglobin curve for normal human blood and for blood containing 50% carboxyhemoglobin (COHb). The top curve shows normal hemoglobin (Hb) dynamics with the red (A) site indicating normal arterial O2 saturation (∼100 mmHg) and a 5 volume % drop to a mixed venous value indicated by the blue (V) to be ∼40 mmHg. In the presence of 50% COHb, although the arterial blood may have a measured value of ∼100 mmHg, the actual O2 saturation is only 50% and a 5 volume % drop results in a mixed venous value indicated by the blue (V) to be ∼16 mmHg. This contrasts with a simple 50% anemia where the mixed venous value would be approximately 26 mmHg. The value of 16 mmHg is due to the “left shift” caused by the impact of COHb on Hb cooperativity.

Figure 3. Figure 3.

This is a figure used with permission from Senozan et al. 298. Lines show predicted changes in tissue carbon monoxide (CO) pressure (PCO) as a function of tissue Po2. The family of curves was generated for different alveolar CO partial pressures from 0.01 to 0.1 Torr assuming an alveolar Po2 value of 100 Torr.

Figure 4. Figure 4.

Schematic illustrating intravascular platelet‐neutrophil events leading to vascular wall oxidative stress. This is a modified figure similar to one in reference 227. Starting with carbon monoxide binding to platelet hemoproteins (at left in figure), platelet‐derived nitric oxide reacts with neutrophil‐derived O2., giving rise to reactive species that activate platelets and cause platelet‐neutrophil aggregates. On‐going interactions involving reactive products and adhesion molecules cause firm aggregation and stimulate intravascular neutrophil degranulation. Myeloperoxidase (MPO) is deposited along the vascular lining and some is transcytosed to the subendothelial matrix. Products from MPO‐mediated reactions cause endothelial cell activation, facilitating firm neutrophil adhesion and further degranulation. Neutrophil‐derived proteases react with endothelial cell constituents exacerbating the vascular insult.

Figure 1.

Schematic depicting interactions between carbon monoxide (CO)/heme oxygenase‐1, and nitric oxide/nitric oxide synthase (NO/NOS). CO generated by HO‐1 can mediate HO‐1 and NOS synthesis in pathways involving several transcription factors (TF's) 76,155,172,193,225,389. HO‐1 synthesis can also be induced by NO (shown with the label “mRNA”), although the mechanism for gene regulation has not been elucidated 50,51,234,244,245. The figure also indicates that CO can inhibit NOS activity, although local concentrations of enzyme substrates and co‐factors have a large impact on CO affinity 1,25,94,192,288,315,381.

Figure 2.

Oxyhemoglobin curve for normal human blood and for blood containing 50% carboxyhemoglobin (COHb). The top curve shows normal hemoglobin (Hb) dynamics with the red (A) site indicating normal arterial O2 saturation (∼100 mmHg) and a 5 volume % drop to a mixed venous value indicated by the blue (V) to be ∼40 mmHg. In the presence of 50% COHb, although the arterial blood may have a measured value of ∼100 mmHg, the actual O2 saturation is only 50% and a 5 volume % drop results in a mixed venous value indicated by the blue (V) to be ∼16 mmHg. This contrasts with a simple 50% anemia where the mixed venous value would be approximately 26 mmHg. The value of 16 mmHg is due to the “left shift” caused by the impact of COHb on Hb cooperativity.

Figure 3.

This is a figure used with permission from Senozan et al. 298. Lines show predicted changes in tissue carbon monoxide (CO) pressure (PCO) as a function of tissue Po2. The family of curves was generated for different alveolar CO partial pressures from 0.01 to 0.1 Torr assuming an alveolar Po2 value of 100 Torr.

Figure 4.

Schematic illustrating intravascular platelet‐neutrophil events leading to vascular wall oxidative stress. This is a modified figure similar to one in reference 227. Starting with carbon monoxide binding to platelet hemoproteins (at left in figure), platelet‐derived nitric oxide reacts with neutrophil‐derived O2., giving rise to reactive species that activate platelets and cause platelet‐neutrophil aggregates. On‐going interactions involving reactive products and adhesion molecules cause firm aggregation and stimulate intravascular neutrophil degranulation. Myeloperoxidase (MPO) is deposited along the vascular lining and some is transcytosed to the subendothelial matrix. Products from MPO‐mediated reactions cause endothelial cell activation, facilitating firm neutrophil adhesion and further degranulation. Neutrophil‐derived proteases react with endothelial cell constituents exacerbating the vascular insult.

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Stephen R. Thom. Carbon Monoxide Transport and Actions in Blood and Tissues. Compr Physiol 2011, 1: 421-446. doi: 10.1002/cphy.c091005