Hypothesis and preliminary data to suggest carbon monoxide as the mediator of the hyperdynamic circulation of cirrhosis?

Hypothesis The mechanisms underlying the 'hyperdynamic circulation' of cirrhosis remain unclear. Excess production of endogenous carbon monoxide (CO) which has recently been described as a vasodilator, may have a role in the circulatory disturbance of cirrhosis. Methods We measured carboxyhaemoglobin (COHb) and plasma cyclic guanylmonophosphate (cGMP) in 22 patients (11 M, mean age 53yr) with cirrhosis and 9 healthy controls (mean age 50yr). All were nonsmokers or abstinent for 14 days. Results COHb was elevated in patients (2.1 ± 0.3%), compared to controls (0.9 ± 0.1%; p = 0.005). Nine patients who underwent elective transjugular intrahepatic portosystemic stent shunting (TIPSS) had high initial COHB levels (3.1 ± 0.4% p = 0.002). However, two weeks after TIPSS, COHb had risen further (4.3 ± 0.3% p = 0.02). Total haemoglobin concentrations were similar in all groups. Simultaneous plasma cGMP levels correlated with COHb (r = 0.72, p = 0.003). Conclusions We have demonstrated that excess endogenous CO production occurs in the vasodilated state of cirrhosis and correlates with a marker of vasodilator tone (cGMP). This supports the hypothesis that CO may be a mediator of the vasodilatation of chronic liver disease.