First evaluation of real-time nitric oxide changes in the coronary circulation in patients with non-ischaemic dilated cardiomyopathy using a catheter-type sensor

Abstract

Aims: No direct method has yet been developed to measure real-time plasma nitric oxide (NO) concentration in humans. In this study, we evaluated a new method for measuring plasma NO concentration in patients with dilated cardiomyopathy (DCM) and in normal controls using a catheter-type sensor.

Methods and results: We simultaneously measured average peak velocity (APV) of the coronary artery flow and change in plasma NO concentration using the NO sensor placed in the great cardiac vein of 10 DCM patients and 10 control subjects. These evaluations were performed in response to sequential intracoronary infusions of acetylcholine (ACh, 10⁻⁸-10⁻⁶ M), N(G)-monomethyl-l-arginine (l-NMMA, 200 µmol) and co-infusion of ACh and l-NMMA. The change in plasma NO concentration in DCM patients was significantly impaired compared with the control group (P < 0.01). Pretreatment with l-NMMA completely suppressed the ACh-induced NO concentration, whereas APV in the left anterior descending coronary artery was partially suppressed in both groups. Plasma NO concentration reached its peak value later than the maximum APV following the injection of ACh (10⁻⁶ M) in both groups.

Conclusion: The catheter-type NO sensor could be applied to clinically evaluate the endothelial function (i.e. reduced endothelium-derived NO bioavailability) in patients with cardiovascular diseases.

Figure 1

X-ray photographs showing the position of the infusion catheter, Doppler wire, and nitric oxide sensor. (A) right anterior oblique (RAO) 30 and (B) left anterior oblique (LAO) 60. The detection tip of the nitric oxide sensor was placed in the great cardiac vein through a 7-Fr Amplatz guiding catheter from the femoral vein. A coronary-infusion catheter was positioned distal to the first major septal branch, while a Doppler guide wire was positioned distal to the infusion catheter to monitor coronary flow velocity.

Figure 2

Study protocol. First, there were three 2-min infusions of acetylcholine (ACh) at 0.15, 1.5, and 15 µg/min via the infusion catheter positioned in the left anterior descending coronary artery. After a 5-min infusion of N^G-monomethyl-l-arginine (l-NMMA) at 40 µmol/min, ACh was infused at the three concentrations as before. Coronary arteriograms were recorded after each injection of ACh and l-NMMA. The coronary flow velocity of the left anterior descending coronary artery was continuously monitored during this protocol.

Figure 3

Representative tracings of real-time nitric oxide concentration in the dilated cardiomyopathy and control groups. Representative tracings of plasma nitric oxide concentration in the great cardiac vein after infusion of (A) ACh 0.3 µg, (B) ACh 3 µg, (C) ACh 30 µg, (D) l-NMMA 200 µmol, and (E) l-NMMA 200 µmol + ACh 30 µg.

Figure 4

Real-time profiles of nitric oxide (NO) concentration and averaged peak velocity. Representative real-time plot of changes in NO concentration and averaged peak velocity in the distal left anterior descending coronary artery (LAD).

Figure 5

Comparative profiles of nitric oxide (NO) concentration and averaged peak velocity. Comparative plot showing changes in NO concentration and averaged peak velocity in 10 dilated cardiomyopathy (DCM) patients and 10 control subjects. Statistical analyses for comparison of changes in plasma NO concentration and averaged peak velocity were conducted by paired t-test. *P < 0.01 compared with time 0.