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Production of Arrhythmias by Elevated Carboxyhemoglobin in Patients with Coronary Artery Disease

David S. Sheps, MD, MSPH; Margaret C. Herbst, MSN; Alan L. Hinderliter, MD; Kirkwood F. Adams, MD; Lars G. Ekelund, MD, PhD; John J. O'Neil, PhD; George M. Goldstein, PhD; Philip A. Bromberg, MD; Janice L. Dalton, BS; Martha N. Ballenger; Sonia M. Davis, MS; and Gary G. Koch, PhD
[+] Article, Author, and Disclosure Information

Grant Support: Conducted under contract to the Health Effects Institute (HEI), an organization jointly funded by the U.S. Environmental Protection Agency (EPA) (Assistance Agreement X-812059) and automotive manufacturers. The contents of this article do not necessarily reflect the views of the HEI, nor do they necessarily reflect the policies of EPA or automotive manufacturers. Also supported in part by the cooperative agreement CR812738 between the U.S. Environmental Protection Agency and the University of North Carolina at Chapel Hill.

Requests for Reprints: David S. Sheps, MD, Division of Cardiology, CB# 7075, Burnett-Womack Building, University of North Carolina, Chapel Hill, NC 27599-7075.

Current Author Addresses: Drs. Sheps, Hinderliter, Adams, and Ekelund: Division of Cardiology, CB# 7075, Burnett-Womack Building, University of North Carolina, Chapel Hill, NC 27599-7075.

Ms. Herbst, Dr. Bromberg, Ms. Dalton, and Ms. Ballenger: Center for Environmental Medicine, CB# 7310, Trailer #4, University of North Carolina, Chapel Hill, NC 27599-7310.

Drs. O'Neil and Goldstein: U.S. Environmental Protection Agency, Human Studies Division, Clinical Research Branch, Health Effects Research Laboratory, Research Triangle Park, NC 27707.

Ms. Davis and Dr. Koch: Department of Biostatistics, CB# 7400, Trailer #39, School of Public Health, University of North Carolina, Chapel Hill, NC 27599-7400.

©1990 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1990;113(5):343-351. doi:10.7326/0003-4819-113-5-343
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Objective: To assess the effects of exposure to 4% and 6% carboxyhemoglobin on ventricular arrhythmias in patients with coronary artery disease.

Design: Randomized, double-blind, crossover design.

Setting: Exercise laboratory with an environmentally controlled exposure.

Patients: Forty-one nonsmokers with documented coronary artery disease.

Intervention: On day 1, a training session with no exposure, the baseline carboxyhemoglobin level was measured, and a supine bicycle exercise test was done. On days 2 to 4, patients were exposed to room air, 100 ppm carbon monoxide (target, 4% carboxyhemoglobin) or 200 ppm carbon monoxide (target, 6% carboxyhemoglobin), and they then did supine bicycle exercise with radionuclide ventriculography. Ambulatory electrocardiogram recordings were made during the 4 consecutive days to determine the frequency of ventricular premature depolarization (VPD) at various intervals.

Measurements and Main Results: The frequency of single VPD/h was significantly greater on the 6% carboxyhemoglobin day than on the room air day during the exercise period (167.72 ± 37.99 for 6% carboxyhemoglobin compared with 127.32 ± 28.22 for room air, P = 0.03). During exercise, the frequency of multiple VPD/h was greater on the 6% carboxyhemoglobin day compared with room air (9.59 ± 3.70 on the 6% carboxyhemoglobin compared with 3.18 ± 1.67 on room air, P = 0.02). Patients who developed increased single VPD during exercise on the 6% carboxyhemoglobin day were significantly older than those who had no increased arrhythmia, whereas patients who developed complex arrhythmias were also older and, in addition, exercised longer and had a higher peak workload during exercise.

Conclusion: The number and complexity of ventricular arrhythmias increases significantly during exercise after carbon monoxide exposure producing 6% carboxyhemoglobin compared with room air but not after exposure producing 4% carboxyhemoglobin.





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