Objective: 

Carbon monoxide (CO) is a toxic gas, which also acts in the organism as a neurotransmitter. It is generated as a by-product of heme breakdown catalyzed by heme oxygenase. We have studied influence of exogenous CO and inhibitor of endogenous CO production zinc protoporphyrin IX on contractile activity in Langendorff-perfused rat heart and electrical activity in rat atrial and ventricular working myocardium and mouse sinoatrial node.

Methods: 

Standard microelectrode technique was used for intracellular registration of action potentials (APs) in isolated preparations of rat right atrium, rat right ventricular wall and mouse sinoatrial node. In Langendorff-perfused isolated hearts left ventricular pressure was registered directly.

Results: 

Solution containing dissolved exogenous CO (100mM-1mM) caused prominent decrease of AP duration in working rat atrial myocardium accompanied with significant acceleration of sinus rhythm and similar decrease of APD in ventricular myocardium. In the mouse sinoatrial node preparations CO (100mM-1mM) produced acceleration of pacemaker activity associated with increase in velocity of slow diastolic depolarization and decrease in AP amplitude. In addition high concentrations of CO (100mM – 300 mM) depressed contractile activity of isolated hearts, while low concentration (50mM) enhanced it. Inhibitor of heme oxygenase zinc protoporphyrin IX (10mM) produced opposite electrophysiological effects: prolongation of AP in atrial and ventricular working myocardium and reduction of sinus rhythm rate. Therefore, endogenous CO, which may be generated in the heart due to the presence of active heme oxygenase, is likely to exert the same effects as exogenous CO applied to the perfusing medium.

Conclusions: 

We conclude that both endogenous and exogenous CO may act as important regulators of electrical and contractile cardiac activity.