Carboxyhemoglobin level of 6% produced by carbon monoxide exposure increased ventricular arrhythmias during exercise in coronary artery disease
ACP J Club. 1991 Jan-Feb;114:27. doi:10.7326/ACPJC-1991-114-1-027
Sheps DS, Herbst MC, Hinderliter AL, et al. Production of arrhythmias by elevated carboxyhemoglobin in patients with coronary artery disease. Ann Intern Med. 1990;113:343-51.
To determine whether a 4% and 6% venous carboxyhemoglobin concentration has an arrhythmogenic effect in patients with coronary heart disease.
Randomized, double-blind, crossover study of 4 days duration.
Exercise laboratory. Patients were recruited from the inpatient and outpatient cardiology services of North Carolina Memorial Hospital and from local outpatient cardiac rehabilitation programs.
46 nonsmokers with documented coronary artery disease were enrolled in the study, of whom 41 had complete data. Patients were excluded if they had coexistent valvular heart disease, major systemic illness, uncontrolled hypertension, orthopedic or peripheral vascular disease precluding bicycle exercise, or a preexposure venous carboxyhemoglobin level greater than 2.5%, or if they were pregnant or taking antiarrhythmic drugs. The analysis group consisted of 36 men and 5 women with mean age of 63 years.
Assessment of risk factors
On days 2 to 4 of the study, patients were exposed to room air or to 100 ppm or 200 ppm carbon monoxide. Once the desired carboxyhemoglobin level was achieved the patient did a supine maximal bicycle exercise test with radionuclide ventriculography. Levels of 4% and 6% were chosen to simulate natural exposure to 50 ppm carbon monoxide between 1 and 8 hours while doing light or heavy exercise, respectively.
Main outcome measure
The frequency of ventricular premature depolarization (VPD) was determined by ambulatory electrocardiogram recordings.
During exercise, the frequency of VPD/h was significantly greater on the 6% carboxyhemoglobin day than on the room air day when all 41 patients were included in the analysis (single VPD/h, 127.16 ± 30.53 [SE] compared with 96.53 ± 22.92, P = 0.02; multiple VPD/h, 7.20 ± 2.85 compared with 2.46 ± 1.30, P = 0.02). Patients who developed complex arrhythmias were significantly older than those who did not have an arrhythmic response (67.1 ± 1.9 y vs 61.4 ± 1.2 y P = 0.02). In addition, the patients exercised longer (1017 ± 83 s vs 797 ± 55 s, P = 0.05) and had a higher peak workload during exercise (500 ± 39 kpm vs 402 ± 25 kpm, P = 0.05).
The number and complexity of ventricular arrhythmias increased significantly during exercise after carbon monoxide exposure producing 6% carboxyhemoglobin compared with room air, but not after exposure producing 4% carboxyhemoglobin.
Sources of funding: The Health Effects Institute and the U.S. Environmental Protection Agency.
Address for article reprint: Dr. D. S. Sheps, Division of Cardiology, CB # 7075, Burnett-Womack Building, University of North Carolina, Chapel Hill, NC 27599-7075, USA.
This study provides new information about the potential role of acute carbon monoxide exposure in inducing ventricular arrhythmias in patients with coronary artery disease. The authors showed an increase in single and complex VPDs during exercise in a small group of men and women under controlled conditions. Caution should be taken in viewing these results; a statistically significant 50% reduction in VPDs noted during the exposure phase of the 4% carboxyhemoglobin day was attributed to background variability (single VPHD/h 35.82 ± 9.99 vs 17.2 ± 4.3, P = 0.03).
Because inducible ischemia was not noted in the group with complex arrhythmias during the 6% carboxyhemoglobin day, the mechanism by which increased exposure to carboxyhemoglobin leads to ventricular arrhythmias remains unclear. Despite these limitations, this study makes an important contribution to our understanding of the potential role of carbon monoxide in causing cardiac arrhythmias in patients with coronary artery disease. Additional work comparing acute and chronic exposure to carbon monoxide as well as exploring the relationship between carbon monoxide and inducible ischemia would be welcome.
Charles B. Eaton, MD
Brown University Memorial HospitalProvidence, Rhode Island, USA