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Mechanism of the toxic action of carbon monoxide
Insights
High carboxyhemoglobin (COHb) levels do not impair blood oxygen capacity. Carbon monoxide (CO) toxicity stems from cellular respiration interference, not COHb levels alone.
Area of Science:
- Toxicology
- Biochemistry
- Physiology
Background:
- Carboxyhemoglobin (COHb) is a marker of carbon monoxide (CO) exposure.
- The direct impact of COHb on oxygen-carrying capacity requires further clarification.
Purpose of the Study:
- To investigate the relationship between COHb levels and CO toxicity.
- To elucidate the primary mechanism of CO toxicity.
Main Methods:
- Transfusion of erythrocytes with high COHb levels in dogs.
- Intraperitoneal injection of carbon monoxide gas in dogs.
- Inhalation of CO gas in dogs.
- Analysis of COHb levels and survival rates.
Main Results:
- High COHb levels (above 50%) did not induce toxicity in dogs via erythrocyte transfusion or CO gas injection.
- Dogs inhaling 13% CO died within 15-65 minutes with an average COHb of 65%.
- CO toxicity is linked to interference with cellular respiration in mitochondria, specifically CO's competition with O2 for cytochrome a3.
Conclusions:
- COHb levels alone are not the sole determinant of CO toxicity.
- CO toxicity primarily results from CO's inhibition of cellular respiration by binding to cytochrome oxidase.
- Dissolved CO in plasma facilitates CO entry into tissues, leading to organ-specific toxicity, particularly in the heart and brain.
Abstract:
Our studies indicate that a high concentration of carboxyhemoglobin (COHb) does not interfere with the O2--carrying capacity of the blood. In dogs, both the transfusion of erythrocytes containing 80 percent COHb and the i.p. injection of carbon monoxide (CO) gas do not produce CO toxicity even though the COHb is above 50 percent. Dogs inhaling CO (13 percent in air) for 15 minutes died within 15 minutes to 65 minutes with an average COHb level of 65 percent. The probable toxic action of CO is on the cellular respiration taking place in the mitochondria when CO competes with O2 for cytochrome a3. The presence of dissolved CO in plasma, which is necessary for CO to enter the tissue, probably occurs when the exchange takes place between alveolar air and the blood in the lungs. When air containing CO is inhaled, there will be a significant CO tension in the blood when it leaves the lungs and when it reaches the organs especially the heart and brain. While COHb level is useful as a clinical measure of CO exposure, the most important mechanism by which CO causes toxicity is its combination with cytochrome oxidase.