BACKGROUND: Carbon monoxide (CO) poisoning remains the leading cause of death by poisoning in the world. One of the major proposed mechanisms for CO toxicity is the binding of CO to cytochrome oxidase and interference with cellular oxygen utilization but evidence for this is inconclusive. AIM OF STUDY: This study examined the effects of prolonged CO exposure on the dynamics of whole body oxygen consumption (VO(2)) and oxygen delivery (DO(2)) in an attempt to observe if CO exposure results in a defect of oxygen utilization defect as determined by a reduction in VO(2) during the course of poisoning prior to reaching the point where VO(2) is directly dependent on DO(2). This critical level of DO(2) (DO(2)crit) produced by CO poisoning was compared to historical values produced by other insults, which decrease global body DO(2). METHODS: Five small dogs were ventilated for 2 h with 0.25% CO and room air followed by 0.5% CO until death. Cardiac index (Q), DO(2), VO(2), oxygen extraction ratio (OER), and systemic lactate were measured every 15 min until death. RESULTS: Carboxyhemoglobin (COHb) levels increased linearly over 2.5 h to values above 80% until death. VO(2) remained constant and not significantly different from baseline below a COHb of 80%. At COHb levels above 80%, VO(2) precipitously dropped. Similarly lactate levels were not significantly elevated from baseline until VO(2) dropped. DO(2) decreased by 78% (from 23+/-6 ml/kg/min to 5+/-4 ml/kg/min) over time despite an increase in Q by 58% until levels of COHb were above 80%. OER increased from 19+/-5% to 50+/-11% until death. The calculated DO(2)crit was 10.7+/-4 ml/min/kg, which is not significantly different from values ranging from 7 to 13 ml/min/kg reported in the literature due to other insults, which reduce DO(2). CONCLUSION: In this canine model of prolonged CO exposure, no gradual reduction in VO(2) or increase in systemic lactate prior to reaching DO(2)crit was noted. In addition, CO exposure does not appear to change the DO(2)crit. The combination of these findings does not support the theory that CO produces a whole body intracellular defect in oxygen utilization.
BACKGROUND:Carbon monoxide (CO) poisoning remains the leading cause of death by poisoning in the world. One of the major proposed mechanisms for CO toxicity is the binding of CO to cytochrome oxidase and interference with cellular oxygen utilization but evidence for this is inconclusive. AIM OF STUDY: This study examined the effects of prolonged CO exposure on the dynamics of whole body oxygen consumption (VO(2)) and oxygen delivery (DO(2)) in an attempt to observe if CO exposure results in a defect of oxygen utilization defect as determined by a reduction in VO(2) during the course of poisoning prior to reaching the point where VO(2) is directly dependent on DO(2). This critical level of DO(2) (DO(2)crit) produced by COpoisoning was compared to historical values produced by other insults, which decrease global body DO(2). METHODS: Five small dogs were ventilated for 2 h with 0.25% CO and room air followed by 0.5% CO until death. Cardiac index (Q), DO(2), VO(2), oxygen extraction ratio (OER), and systemic lactate were measured every 15 min until death. RESULTS: Carboxyhemoglobin (COHb) levels increased linearly over 2.5 h to values above 80% until death. VO(2) remained constant and not significantly different from baseline below a COHb of 80%. At COHb levels above 80%, VO(2) precipitously dropped. Similarly lactate levels were not significantly elevated from baseline until VO(2) dropped. DO(2) decreased by 78% (from 23+/-6 ml/kg/min to 5+/-4 ml/kg/min) over time despite an increase in Q by 58% until levels of COHb were above 80%. OER increased from 19+/-5% to 50+/-11% until death. The calculated DO(2)crit was 10.7+/-4 ml/min/kg, which is not significantly different from values ranging from 7 to 13 ml/min/kg reported in the literature due to other insults, which reduce DO(2). CONCLUSION: In this canine model of prolonged CO exposure, no gradual reduction in VO(2) or increase in systemic lactate prior to reaching DO(2)crit was noted. In addition, CO exposure does not appear to change the DO(2)crit. The combination of these findings does not support the theory that CO produces a whole body intracellular defect in oxygen utilization.
Authors: Therese Hornstrup; F T Løwenstein; M A Larsen; E W Helge; S Póvoas; J W Helge; J J Nielsen; B Fristrup; J L Andersen; L Gliemann; L Nybo; P Krustrup Journal: Eur J Appl Physiol Date: 2018-11-24 Impact factor: 3.078
Authors: Jason J Rose; Ling Wang; Qinzi Xu; Charles F McTiernan; Sruti Shiva; Jesus Tejero; Mark T Gladwin Journal: Am J Respir Crit Care Med Date: 2017-03-01 Impact factor: 21.405
Authors: Jason J Rose; Kaitlin A Bocian; Qinzi Xu; Ling Wang; Anthony W DeMartino; Xiukai Chen; Catherine G Corey; Danielle A Guimarães; Ivan Azarov; Xueyin N Huang; Qin Tong; Lanping Guo; Mehdi Nouraie; Charles F McTiernan; Christopher P O'Donnell; Jesús Tejero; Sruti Shiva; Mark T Gladwin Journal: J Biol Chem Date: 2020-03-23 Impact factor: 5.157
Authors: Ying Cheng; Adia Thomas; Feras Mardini; Shannon L Bianchi; Junxia X Tang; Jun Peng; Huafeng Wei; Maryellen F Eckenhoff; Roderic G Eckenhoff; Richard J Levy Journal: PLoS One Date: 2012-02-10 Impact factor: 3.240