The impact of low-level carbon monoxide exposure on ventricular arrhythmia frequency in patients with ischemic heart disease has not been thoroughly studied. The issue is of concern because of the potential proarrhythmic effect of carbon monoxide in patients with ischemic heart disease. We studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. By using appropriate inclusion and exclusion criteria, subjects were selected and enrolled in a randomized double-blind study to determine the effects of carbon monoxide exposure on ventricular arrhythmia frequency at rest, during exercise, and during ambulatory activities. The carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. The carbon monoxide exposure protocol produced target levels in 60 minutes, and the levels were maintained for an additional 90 minutes to provide adequate time to assess the impact of carbon monoxide on the frequency of ventricular ectopic beats. The data on total and repetitive ventricular arrhythmias were analyzed for seven specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide or air exposure; (3) during a two-hour rest period; (4) during an exercise period; (5) during an exercise recovery period; (6) six hours after carbon monoxide or air exposure; and (7) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity. During steady-state conditions at rest, the number of ventricular ectopic beats per hour was 115 +/- 153 (SD) for room air exposure (0.7% carboxyhemoglobin), 121 +/- 171 for the lower carbon monoxide exposure (3.2% carboxyhemoglobin), and 94 +/- 129 for the higher carbon monoxide exposure (5.1% carboxyhemoglobin). The frequency of complex ventricular ectopy was not altered at the levels of carbon monoxide studied. Secondary analysis of the impact of carbon monoxide on ventricular ectopic beat frequency stratified by baseline ejection fraction, baseline ventricular ectopic beat frequency, and exercise-induced ST-segment changes did not indicate an effect of carbon monoxide on ventricular arrhythmias. In conclusion, low levels of carbon monoxide exposure resulting in blood levels of 3.2% and 5.1% carboxyhemoglobin, as measured by gas chromatography, do not have a proarrhythmic effect on patients with coronary artery disease and frequent ventricular ectopy.(ABSTRACT TRUNCATED AT 400 WORDS)