Myocardial dysfunction and potential cardiac hypoxia in rats induced by carbon monoxide inhalation.
BACKGROUND
Results from both animal and human being studies provide evidence that inhalation of concentrations of carbon monoxide (CO) at around 100 ppm has antiinflammatory effects. These low levels of CO are incriminated in ischemic heart diseases experienced by cigarette smokers and, in some cases, from air pollution. Although neurologic mechanisms have been investigated, the effects of CO on cardiovascular function are still poorly understood.


RESULTS
The effects of CO (250 ppm; 90 min) inhalation on myocardial function were investigated in isolated heart of rats killed immediately, and 3, 24, 48, and 96 h after CO exposure. CO exposure at 250 ppm resulted in an arterial carboxyhemoglobin (HbCO) level of approximately 11%, which was not associated with changes in mean arterial pressure and heart rate. CO exposure induced coronary perfusion pressure increases, which were associated with endothelium-dependent and -independent vascular relaxation abnormalities. CO-induced coronary vascular relaxation perturbations were observed in the presence of increased heart contractility. Spontaneous peak to maximal Ca(2+)-activated left ventricular pressure ratio was markedly increased in CO-exposed rats, indicating increases in myofilament calcium sensitivity. Heart cyclic guanosine monophosphate/cAMP ratio and myocardial permeabilized fiber respiration (complex intravenous activity) were reduced in CO-exposed rats, which lasted after 48 h of reoxygenation in air.


CONCLUSIONS
These findings suggest that CO deteriorates heart oxygen supply to utilization and potentially may induce myocardial hypoxia through mechanisms that include increased oxygen demand due to increased contractility, reduced coronary blood flow reserve, and cardiomyocyte respiration inhibition.
Favory
Raphaël
R
Intensive Care Unit and Hyperbaric Regional Center, University Hospital of Lille, Lille, France.
Lancel
Steve
S
Tissier
Stéphanie
S
Mathieu
Daniel
D
Decoster
Brigitte
B
Nevière
Rémi
R
D000280:Administration, Inhalation; D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000009:adverse effects*; D002263:Carboxyhemoglobin / Q000032:analysis; D003326:Coronary Circulation / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood*; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects
D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D000242:Cyclic AMP; D006152:Cyclic GMP; D010100:Oxygen